Full text data of GDI1
GDI1
(GDIL, OPHN2, RABGDIA, XAP4)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Rab GDP dissociation inhibitor alpha; Rab GDI alpha (Guanosine diphosphate dissociation inhibitor 1; GDI-1; Oligophrenin-2; Protein XAP-4)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Rab GDP dissociation inhibitor alpha; Rab GDI alpha (Guanosine diphosphate dissociation inhibitor 1; GDI-1; Oligophrenin-2; Protein XAP-4)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00010154
IPI00010154 Rab GDP dissociation inhibitor alpha Rab GDP dissociation inhibitor alpha membrane n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a expected molecular weight found in band > 188 kDa together with ubiquitin
IPI00010154 Rab GDP dissociation inhibitor alpha Rab GDP dissociation inhibitor alpha membrane n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a expected molecular weight found in band > 188 kDa together with ubiquitin
UniProt
P31150
ID GDIA_HUMAN Reviewed; 447 AA.
AC P31150; P50394; Q6FG50; Q7Z2G6; Q7Z2G9; Q7Z2H5; Q7Z2I6;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Rab GDP dissociation inhibitor alpha;
DE Short=Rab GDI alpha;
DE AltName: Full=Guanosine diphosphate dissociation inhibitor 1;
DE Short=GDI-1;
DE AltName: Full=Oligophrenin-2;
DE AltName: Full=Protein XAP-4;
GN Name=GDI1; Synonyms=GDIL, OPHN2, RABGDIA, XAP4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=7849400; DOI=10.1007/BF00411459;
RA Sedlacek Z., Konecki D.S., Korn B., Klauck S.M., Poustka A.;
RT "Evolutionary conservation and genomic organization of XAP-4, an Xq28
RT located gene coding for a human rab GDP-dissociation inhibitor
RT (GDI).";
RL Mamm. Genome 5:633-639(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=7585614;
RA Nishimura N., Goji J., Nakamura H., Orita S., Takai Y., Sano K.;
RT "Cloning of a brain-type isoform of human Rab GDI and its expression
RT in human neuroblastoma cell lines and tumor specimens.";
RL Cancer Res. 55:5445-5450(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=8733135; DOI=10.1093/hmg/5.5.659;
RA Chen E.Y., Zollo M., Mazzarella R.A., Ciccodicola A., Chen C.-N.,
RA Zuo L., Heiner C., Burough F.W., Ripetto M., Schlessinger D.,
RA D'Urso M.;
RT "Long-range sequence analysis in Xq28: thirteen known and six
RT candidate genes in 219.4 kb of high GC DNA between the RCP/GCP and
RT G6PD loci.";
RL Hum. Mol. Genet. 5:659-668(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Feng Z., Zhang B., Zhou Y., Peng X., Yuan J., Qiang B.;
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=12777533; DOI=10.1093/molbev/msg134;
RA Kitano T., Schwarz C., Nickel B., Paeaebo S.;
RT "Gene diversity patterns at 10 X-chromosomal loci in humans and
RT chimpanzees.";
RL Mol. Biol. Evol. 20:1281-1289(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 143-181.
RA Hochgeschwender U.;
RT "Rapid identification of gene sequences for transcriptional map
RT assembly by direct cDNA screening of genomic reference libraries.";
RL Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP PROTEIN SEQUENCE OF 143-156; 174-193 AND 222-240, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 328-436.
RA Bhat K.S.;
RL Submitted (NOV-1992) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP PROTEIN SEQUENCE OF 349-361.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [15]
RP TISSUE SPECIFICITY.
RX PubMed=7543319; DOI=10.1093/hmg/4.4.701;
RA Bachner D., Sedlacek Z., Korn B., Hameister H., Poustka A.;
RT "Expression patterns of two human genes coding for different rab GDP-
RT dissociation inhibitors (GDIs), extremely conserved proteins involved
RT in cellular transport.";
RL Hum. Mol. Genet. 4:701-708(1995).
RN [16]
RP INTERACTION WITH RHOH.
RX PubMed=11809807; DOI=10.1128/MCB.22.4.1158-1171.2002;
RA Li X., Bu X., Lu B., Avraham H., Flavell R.A., Lim B.;
RT "The hematopoiesis-specific GTP-binding protein RhoH is GTPase
RT deficient and modulates activities of other Rho GTPases by an
RT inhibitory function.";
RL Mol. Cell. Biol. 22:1158-1171(2002).
RN [17]
RP INTERACTION WITH RAB10.
RX PubMed=19570034; DOI=10.1042/BJ20090624;
RA Chen Y., Deng Y., Zhang J., Yang L., Xie X., Xu T.;
RT "GDI-1 preferably interacts with Rab10 in insulin-stimulated GLUT4
RT translocation.";
RL Biochem. J. 422:229-235(2009).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP VARIANT MRX41 PRO-92.
RX PubMed=9620768; DOI=10.1038/487;
RA D'Adamo P., Menegon A., Lo Nigro C., Grasso M., Gulisano M.,
RA Tamanini F., Bienvenu T., Gedeon A.K., Oostra B., Wu S.-K., Tandon A.,
RA Valtorta F., Balch W.E., Chelly J., Toniolo D.;
RT "Mutations in GDI1 are responsible for X-linked non-specific mental
RT retardation.";
RL Nat. Genet. 19:134-139(1998).
RN [20]
RP VARIANT MRX41 PRO-423.
RX PubMed=9668174; DOI=10.1093/hmg/7.8.1311;
RA Bienvenu T., Des Portes V., Saint Martin A., McDonell N., Billuart P.,
RA Carrie A., Vinet M.-C., Couvert P., Toniolo D., Ropers H.-H.,
RA Moraine C., van Bokhoven H., Fryns J.-P., Kahn A., Beldjord C.,
RA Chelly J.;
RT "Non-specific X-linked semidominant mental retardation by mutations in
RT a Rab GDP-dissociation inhibitor.";
RL Hum. Mol. Genet. 7:1311-1315(1998).
CC -!- FUNCTION: Regulates the GDP/GTP exchange reaction of most Rab
CC proteins by inhibiting the dissociation of GDP from them, and the
CC subsequent binding of GTP to them.
CC -!- SUBUNIT: Interacts with RHOH. Interacts with RAB10; negatively
CC regulates RAB10 association with membranes and activation.
CC -!- INTERACTION:
CC P61027:Rab10 (xeno); NbExp=3; IntAct=EBI-946999, EBI-911581;
CC P20338:RAB4A; NbExp=2; IntAct=EBI-946999, EBI-722284;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- TISSUE SPECIFICITY: Brain; predominant in neural and sensory
CC tissues.
CC -!- DISEASE: Mental retardation, X-linked 41 (MRX41) [MIM:300849]: A
CC disorder characterized by significantly below average general
CC intellectual functioning associated with impairments in adaptive
CC behavior and manifested during the developmental period.
CC Intellectual deficiency is the only primary symptom of non-
CC syndromic X-linked mental retardation, while syndromic mental
CC retardation presents with associated physical, neurological and/or
CC psychiatric manifestations. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Rab GDI family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MRX3";
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DR EMBL; X79353; CAA55908.1; -; mRNA.
DR EMBL; X79354; CAA55909.1; -; Genomic_DNA.
DR EMBL; X79355; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79356; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79357; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79358; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79359; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79360; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79364; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79361; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79362; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79363; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; D45021; BAA08078.1; -; mRNA.
DR EMBL; L44140; AAA92648.1; -; Genomic_DNA.
DR EMBL; AF400433; AAK92482.1; -; mRNA.
DR EMBL; AB101741; BAC80330.1; -; Genomic_DNA.
DR EMBL; AB101742; BAC80331.1; -; Genomic_DNA.
DR EMBL; AB101743; BAC80332.1; -; Genomic_DNA.
DR EMBL; AB101744; BAC80333.1; -; Genomic_DNA.
DR EMBL; AB101745; BAC80334.1; -; Genomic_DNA.
DR EMBL; AB101746; BAC80335.1; -; Genomic_DNA.
DR EMBL; AB101747; BAC80336.1; -; Genomic_DNA.
DR EMBL; AB101748; BAC80337.1; -; Genomic_DNA.
DR EMBL; AB101749; BAC80338.1; -; Genomic_DNA.
DR EMBL; AB101750; BAC80339.1; -; Genomic_DNA.
DR EMBL; AB101751; BAC80340.1; -; Genomic_DNA.
DR EMBL; AB101752; BAC80341.1; -; Genomic_DNA.
DR EMBL; AB101753; BAC80342.1; -; Genomic_DNA.
DR EMBL; AB101754; BAC80343.1; -; Genomic_DNA.
DR EMBL; AB101755; BAC80344.1; -; Genomic_DNA.
DR EMBL; AB101756; BAC80345.1; -; Genomic_DNA.
DR EMBL; AB101757; BAC80346.1; -; Genomic_DNA.
DR EMBL; AB101758; BAC80347.1; -; Genomic_DNA.
DR EMBL; AB101759; BAC80348.1; -; Genomic_DNA.
DR EMBL; AB101760; BAC80349.1; -; Genomic_DNA.
DR EMBL; AB101771; BAC80360.1; -; Genomic_DNA.
DR EMBL; AB101772; BAC80361.1; -; Genomic_DNA.
DR EMBL; AB101773; BAC80362.1; -; Genomic_DNA.
DR EMBL; AB101774; BAC80363.1; -; Genomic_DNA.
DR EMBL; AB101775; BAC80364.1; -; Genomic_DNA.
DR EMBL; AB101776; BAC80365.1; -; Genomic_DNA.
DR EMBL; AB101777; BAC80366.1; -; Genomic_DNA.
DR EMBL; AB101778; BAC80367.1; -; Genomic_DNA.
DR EMBL; AB101779; BAC80368.1; -; Genomic_DNA.
DR EMBL; AB101780; BAC80369.1; -; Genomic_DNA.
DR EMBL; AB101781; BAC80370.1; -; Genomic_DNA.
DR EMBL; AB101782; BAC80371.1; -; Genomic_DNA.
DR EMBL; AB101783; BAC80372.1; -; Genomic_DNA.
DR EMBL; AB101784; BAC80373.1; -; Genomic_DNA.
DR EMBL; AB101785; BAC80374.1; -; Genomic_DNA.
DR EMBL; AB101786; BAC80375.1; -; Genomic_DNA.
DR EMBL; AB101787; BAC80376.1; -; Genomic_DNA.
DR EMBL; AB101788; BAC80377.1; -; Genomic_DNA.
DR EMBL; AB101789; BAC80378.1; -; Genomic_DNA.
DR EMBL; AB101790; BAC80379.1; -; Genomic_DNA.
DR EMBL; AB101801; BAC80390.1; -; Genomic_DNA.
DR EMBL; AB101802; BAC80391.1; -; Genomic_DNA.
DR EMBL; AB101803; BAC80392.1; -; Genomic_DNA.
DR EMBL; AB101804; BAC80393.1; -; Genomic_DNA.
DR EMBL; AB101805; BAC80394.1; -; Genomic_DNA.
DR EMBL; AB101806; BAC80395.1; -; Genomic_DNA.
DR EMBL; AB101807; BAC80396.1; -; Genomic_DNA.
DR EMBL; AB101808; BAC80397.1; -; Genomic_DNA.
DR EMBL; AB101809; BAC80398.1; -; Genomic_DNA.
DR EMBL; AB101810; BAC80399.1; -; Genomic_DNA.
DR EMBL; AB101811; BAC80400.1; -; Genomic_DNA.
DR EMBL; AB101812; BAC80401.1; -; Genomic_DNA.
DR EMBL; AB101813; BAC80402.1; -; Genomic_DNA.
DR EMBL; AB101814; BAC80403.1; -; Genomic_DNA.
DR EMBL; AB101815; BAC80404.1; -; Genomic_DNA.
DR EMBL; AB101816; BAC80405.1; -; Genomic_DNA.
DR EMBL; AB101817; BAC80406.1; -; Genomic_DNA.
DR EMBL; AB101818; BAC80407.1; -; Genomic_DNA.
DR EMBL; AB101819; BAC80408.1; -; Genomic_DNA.
DR EMBL; AB101820; BAC80409.1; -; Genomic_DNA.
DR EMBL; AB101831; BAC80420.1; -; Genomic_DNA.
DR EMBL; AB101832; BAC80421.1; -; Genomic_DNA.
DR EMBL; AB101833; BAC80422.1; -; Genomic_DNA.
DR EMBL; AB101834; BAC80423.1; -; Genomic_DNA.
DR EMBL; AB101835; BAC80424.1; -; Genomic_DNA.
DR EMBL; AB101836; BAC80425.1; -; Genomic_DNA.
DR EMBL; AB101837; BAC80426.1; -; Genomic_DNA.
DR EMBL; AB101838; BAC80427.1; -; Genomic_DNA.
DR EMBL; AB101839; BAC80428.1; -; Genomic_DNA.
DR EMBL; AB101840; BAC80429.1; -; Genomic_DNA.
DR EMBL; AB101841; BAC80430.1; -; Genomic_DNA.
DR EMBL; AB101842; BAC80431.1; -; Genomic_DNA.
DR EMBL; AB101843; BAC80432.1; -; Genomic_DNA.
DR EMBL; AB101844; BAC80433.1; -; Genomic_DNA.
DR EMBL; AB101845; BAC80434.1; -; Genomic_DNA.
DR EMBL; AB101846; BAC80435.1; -; Genomic_DNA.
DR EMBL; AB101847; BAC80436.1; -; Genomic_DNA.
DR EMBL; AB101848; BAC80437.1; -; Genomic_DNA.
DR EMBL; AB101849; BAC80438.1; -; Genomic_DNA.
DR EMBL; AB101850; BAC80439.1; -; Genomic_DNA.
DR EMBL; AB102647; BAC81116.1; -; mRNA.
DR EMBL; CR542258; CAG47054.1; -; mRNA.
DR EMBL; CR542276; CAG47072.1; -; mRNA.
DR EMBL; BT019884; AAV38687.1; -; mRNA.
DR EMBL; BX936385; CAI95780.1; -; Genomic_DNA.
DR EMBL; CH471172; EAW72710.1; -; Genomic_DNA.
DR EMBL; BC000317; AAH00317.1; -; mRNA.
DR EMBL; BC012201; AAH12201.1; -; mRNA.
DR EMBL; U14623; AAA21558.1; -; Genomic_DNA.
DR EMBL; L05086; AAC15851.1; -; mRNA.
DR PIR; I37082; I37082.
DR RefSeq; NP_001484.1; NM_001493.2.
DR UniGene; Hs.595950; -.
DR UniGene; Hs.74576; -.
DR ProteinModelPortal; P31150; -.
DR SMR; P31150; 1-430.
DR IntAct; P31150; 11.
DR MINT; MINT-2859157; -.
DR STRING; 9606.ENSP00000394071; -.
DR PhosphoSite; P31150; -.
DR DMDM; 1707886; -.
DR OGP; P31150; -.
DR REPRODUCTION-2DPAGE; IPI00010154; -.
DR UCD-2DPAGE; P31150; -.
DR PaxDb; P31150; -.
DR PeptideAtlas; P31150; -.
DR PRIDE; P31150; -.
DR DNASU; 2664; -.
DR Ensembl; ENST00000447750; ENSP00000394071; ENSG00000203879.
DR Ensembl; ENST00000601899; ENSP00000471186; ENSG00000268690.
DR GeneID; 2664; -.
DR KEGG; hsa:2664; -.
DR UCSC; uc004fli.4; human.
DR CTD; 2664; -.
DR GeneCards; GC0XP153665; -.
DR H-InvDB; HIX0056464; -.
DR HGNC; HGNC:4226; GDI1.
DR HPA; CAB012979; -.
DR HPA; HPA049290; -.
DR MIM; 300104; gene.
DR MIM; 300849; phenotype.
DR neXtProt; NX_P31150; -.
DR Orphanet; 777; X-linked non-syndromic intellectual deficit.
DR PharmGKB; PA28641; -.
DR eggNOG; COG5044; -.
DR HOVERGEN; HBG000839; -.
DR InParanoid; P31150; -.
DR KO; K17255; -.
DR OMA; FGLDKNT; -.
DR Reactome; REACT_111102; Signal Transduction.
DR ChiTaRS; GDI1; human.
DR GeneWiki; GDI1; -.
DR GenomeRNAi; 2664; -.
DR NextBio; 10512; -.
DR PRO; PR:P31150; -.
DR ArrayExpress; P31150; -.
DR Bgee; P31150; -.
DR CleanEx; HS_GDI1; -.
DR Genevestigator; P31150; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR GO; GO:0005092; F:GDP-dissociation inhibitor activity; TAS:ProtInc.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0005093; F:Rab GDP-dissociation inhibitor activity; IEA:Ensembl.
DR GO; GO:0050771; P:negative regulation of axonogenesis; ISS:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:GOC.
DR GO; GO:0015031; P:protein transport; IEA:InterPro.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome.
DR InterPro; IPR018203; GDP_dissociation_inhibitor.
DR InterPro; IPR000806; RabGDI.
DR Pfam; PF00996; GDI; 1.
DR PRINTS; PR00892; RABGDI.
DR PRINTS; PR00891; RABGDIREP.
PE 1: Evidence at protein level;
KW Complete proteome; Cytoplasm; Direct protein sequencing;
KW Disease mutation; GTPase activation; Mental retardation;
KW Reference proteome.
FT CHAIN 1 447 Rab GDP dissociation inhibitor alpha.
FT /FTId=PRO_0000056671.
FT VARIANT 92 92 L -> P (in MRX41; causes reduced binding
FT and recycling of RAB3A).
FT /FTId=VAR_008130.
FT VARIANT 423 423 R -> P (in MRX41).
FT /FTId=VAR_008131.
FT CONFLICT 34 34 D -> G (in Ref. 2; BAA08078).
FT CONFLICT 36 36 N -> K (in Ref. 2; BAA08078).
FT CONFLICT 149 151 NFD -> GTY (in Ref. 2; BAA08078).
FT CONFLICT 347 347 G -> V (in Ref. 13; AAC15851).
FT CONFLICT 409 409 H -> Q (in Ref. 13; AAC15851).
FT CONFLICT 416 416 D -> G (in Ref. 13; AAC15851).
FT CONFLICT 442 442 F -> S (in Ref. 2; BAA08078).
SQ SEQUENCE 447 AA; 50583 MW; BC283A445E50A652 CRC64;
MDEEYDVIVL GTGLTECILS GIMSVNGKKV LHMDRNPYYG GESSSITPLE ELYKRFQLLE
GPPESMGRGR DWNVDLIPKF LMANGQLVKM LLYTEVTRYL DFKVVEGSFV YKGGKIYKVP
STETEALASN LMGMFEKRRF RKFLVFVANF DENDPKTFEG VDPQTTSMRD VYRKFDLGQD
VIDFTGHALA LYRTDDYLDQ PCLETVNRIK LYSESLARYG KSPYLYPLYG LGELPQGFAR
LSAIYGGTYM LNKPVDDIIM ENGKVVGVKS EGEVARCKQL ICDPSYIPDR VRKAGQVIRI
ICILSHPIKN TNDANSCQII IPQNQVNRKS DIYVCMISYA HNVAAQGKYI AIASTTVETT
DPEKEVEPAL ELLEPIDQKF VAISDLYEPI DDGCESQVFC SCSYDATTHF ETTCNDIKDI
YKRMAGTAFD FENMKRKQND VFGEAEQ
//
ID GDIA_HUMAN Reviewed; 447 AA.
AC P31150; P50394; Q6FG50; Q7Z2G6; Q7Z2G9; Q7Z2H5; Q7Z2I6;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Rab GDP dissociation inhibitor alpha;
DE Short=Rab GDI alpha;
DE AltName: Full=Guanosine diphosphate dissociation inhibitor 1;
DE Short=GDI-1;
DE AltName: Full=Oligophrenin-2;
DE AltName: Full=Protein XAP-4;
GN Name=GDI1; Synonyms=GDIL, OPHN2, RABGDIA, XAP4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=7849400; DOI=10.1007/BF00411459;
RA Sedlacek Z., Konecki D.S., Korn B., Klauck S.M., Poustka A.;
RT "Evolutionary conservation and genomic organization of XAP-4, an Xq28
RT located gene coding for a human rab GDP-dissociation inhibitor
RT (GDI).";
RL Mamm. Genome 5:633-639(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=7585614;
RA Nishimura N., Goji J., Nakamura H., Orita S., Takai Y., Sano K.;
RT "Cloning of a brain-type isoform of human Rab GDI and its expression
RT in human neuroblastoma cell lines and tumor specimens.";
RL Cancer Res. 55:5445-5450(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=8733135; DOI=10.1093/hmg/5.5.659;
RA Chen E.Y., Zollo M., Mazzarella R.A., Ciccodicola A., Chen C.-N.,
RA Zuo L., Heiner C., Burough F.W., Ripetto M., Schlessinger D.,
RA D'Urso M.;
RT "Long-range sequence analysis in Xq28: thirteen known and six
RT candidate genes in 219.4 kb of high GC DNA between the RCP/GCP and
RT G6PD loci.";
RL Hum. Mol. Genet. 5:659-668(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Feng Z., Zhang B., Zhou Y., Peng X., Yuan J., Qiang B.;
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=12777533; DOI=10.1093/molbev/msg134;
RA Kitano T., Schwarz C., Nickel B., Paeaebo S.;
RT "Gene diversity patterns at 10 X-chromosomal loci in humans and
RT chimpanzees.";
RL Mol. Biol. Evol. 20:1281-1289(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 143-181.
RA Hochgeschwender U.;
RT "Rapid identification of gene sequences for transcriptional map
RT assembly by direct cDNA screening of genomic reference libraries.";
RL Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP PROTEIN SEQUENCE OF 143-156; 174-193 AND 222-240, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 328-436.
RA Bhat K.S.;
RL Submitted (NOV-1992) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP PROTEIN SEQUENCE OF 349-361.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [15]
RP TISSUE SPECIFICITY.
RX PubMed=7543319; DOI=10.1093/hmg/4.4.701;
RA Bachner D., Sedlacek Z., Korn B., Hameister H., Poustka A.;
RT "Expression patterns of two human genes coding for different rab GDP-
RT dissociation inhibitors (GDIs), extremely conserved proteins involved
RT in cellular transport.";
RL Hum. Mol. Genet. 4:701-708(1995).
RN [16]
RP INTERACTION WITH RHOH.
RX PubMed=11809807; DOI=10.1128/MCB.22.4.1158-1171.2002;
RA Li X., Bu X., Lu B., Avraham H., Flavell R.A., Lim B.;
RT "The hematopoiesis-specific GTP-binding protein RhoH is GTPase
RT deficient and modulates activities of other Rho GTPases by an
RT inhibitory function.";
RL Mol. Cell. Biol. 22:1158-1171(2002).
RN [17]
RP INTERACTION WITH RAB10.
RX PubMed=19570034; DOI=10.1042/BJ20090624;
RA Chen Y., Deng Y., Zhang J., Yang L., Xie X., Xu T.;
RT "GDI-1 preferably interacts with Rab10 in insulin-stimulated GLUT4
RT translocation.";
RL Biochem. J. 422:229-235(2009).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP VARIANT MRX41 PRO-92.
RX PubMed=9620768; DOI=10.1038/487;
RA D'Adamo P., Menegon A., Lo Nigro C., Grasso M., Gulisano M.,
RA Tamanini F., Bienvenu T., Gedeon A.K., Oostra B., Wu S.-K., Tandon A.,
RA Valtorta F., Balch W.E., Chelly J., Toniolo D.;
RT "Mutations in GDI1 are responsible for X-linked non-specific mental
RT retardation.";
RL Nat. Genet. 19:134-139(1998).
RN [20]
RP VARIANT MRX41 PRO-423.
RX PubMed=9668174; DOI=10.1093/hmg/7.8.1311;
RA Bienvenu T., Des Portes V., Saint Martin A., McDonell N., Billuart P.,
RA Carrie A., Vinet M.-C., Couvert P., Toniolo D., Ropers H.-H.,
RA Moraine C., van Bokhoven H., Fryns J.-P., Kahn A., Beldjord C.,
RA Chelly J.;
RT "Non-specific X-linked semidominant mental retardation by mutations in
RT a Rab GDP-dissociation inhibitor.";
RL Hum. Mol. Genet. 7:1311-1315(1998).
CC -!- FUNCTION: Regulates the GDP/GTP exchange reaction of most Rab
CC proteins by inhibiting the dissociation of GDP from them, and the
CC subsequent binding of GTP to them.
CC -!- SUBUNIT: Interacts with RHOH. Interacts with RAB10; negatively
CC regulates RAB10 association with membranes and activation.
CC -!- INTERACTION:
CC P61027:Rab10 (xeno); NbExp=3; IntAct=EBI-946999, EBI-911581;
CC P20338:RAB4A; NbExp=2; IntAct=EBI-946999, EBI-722284;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- TISSUE SPECIFICITY: Brain; predominant in neural and sensory
CC tissues.
CC -!- DISEASE: Mental retardation, X-linked 41 (MRX41) [MIM:300849]: A
CC disorder characterized by significantly below average general
CC intellectual functioning associated with impairments in adaptive
CC behavior and manifested during the developmental period.
CC Intellectual deficiency is the only primary symptom of non-
CC syndromic X-linked mental retardation, while syndromic mental
CC retardation presents with associated physical, neurological and/or
CC psychiatric manifestations. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Rab GDI family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MRX3";
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DR EMBL; X79353; CAA55908.1; -; mRNA.
DR EMBL; X79354; CAA55909.1; -; Genomic_DNA.
DR EMBL; X79355; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79356; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79357; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79358; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79359; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79360; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79364; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79361; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79362; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; X79363; CAA55909.1; JOINED; Genomic_DNA.
DR EMBL; D45021; BAA08078.1; -; mRNA.
DR EMBL; L44140; AAA92648.1; -; Genomic_DNA.
DR EMBL; AF400433; AAK92482.1; -; mRNA.
DR EMBL; AB101741; BAC80330.1; -; Genomic_DNA.
DR EMBL; AB101742; BAC80331.1; -; Genomic_DNA.
DR EMBL; AB101743; BAC80332.1; -; Genomic_DNA.
DR EMBL; AB101744; BAC80333.1; -; Genomic_DNA.
DR EMBL; AB101745; BAC80334.1; -; Genomic_DNA.
DR EMBL; AB101746; BAC80335.1; -; Genomic_DNA.
DR EMBL; AB101747; BAC80336.1; -; Genomic_DNA.
DR EMBL; AB101748; BAC80337.1; -; Genomic_DNA.
DR EMBL; AB101749; BAC80338.1; -; Genomic_DNA.
DR EMBL; AB101750; BAC80339.1; -; Genomic_DNA.
DR EMBL; AB101751; BAC80340.1; -; Genomic_DNA.
DR EMBL; AB101752; BAC80341.1; -; Genomic_DNA.
DR EMBL; AB101753; BAC80342.1; -; Genomic_DNA.
DR EMBL; AB101754; BAC80343.1; -; Genomic_DNA.
DR EMBL; AB101755; BAC80344.1; -; Genomic_DNA.
DR EMBL; AB101756; BAC80345.1; -; Genomic_DNA.
DR EMBL; AB101757; BAC80346.1; -; Genomic_DNA.
DR EMBL; AB101758; BAC80347.1; -; Genomic_DNA.
DR EMBL; AB101759; BAC80348.1; -; Genomic_DNA.
DR EMBL; AB101760; BAC80349.1; -; Genomic_DNA.
DR EMBL; AB101771; BAC80360.1; -; Genomic_DNA.
DR EMBL; AB101772; BAC80361.1; -; Genomic_DNA.
DR EMBL; AB101773; BAC80362.1; -; Genomic_DNA.
DR EMBL; AB101774; BAC80363.1; -; Genomic_DNA.
DR EMBL; AB101775; BAC80364.1; -; Genomic_DNA.
DR EMBL; AB101776; BAC80365.1; -; Genomic_DNA.
DR EMBL; AB101777; BAC80366.1; -; Genomic_DNA.
DR EMBL; AB101778; BAC80367.1; -; Genomic_DNA.
DR EMBL; AB101779; BAC80368.1; -; Genomic_DNA.
DR EMBL; AB101780; BAC80369.1; -; Genomic_DNA.
DR EMBL; AB101781; BAC80370.1; -; Genomic_DNA.
DR EMBL; AB101782; BAC80371.1; -; Genomic_DNA.
DR EMBL; AB101783; BAC80372.1; -; Genomic_DNA.
DR EMBL; AB101784; BAC80373.1; -; Genomic_DNA.
DR EMBL; AB101785; BAC80374.1; -; Genomic_DNA.
DR EMBL; AB101786; BAC80375.1; -; Genomic_DNA.
DR EMBL; AB101787; BAC80376.1; -; Genomic_DNA.
DR EMBL; AB101788; BAC80377.1; -; Genomic_DNA.
DR EMBL; AB101789; BAC80378.1; -; Genomic_DNA.
DR EMBL; AB101790; BAC80379.1; -; Genomic_DNA.
DR EMBL; AB101801; BAC80390.1; -; Genomic_DNA.
DR EMBL; AB101802; BAC80391.1; -; Genomic_DNA.
DR EMBL; AB101803; BAC80392.1; -; Genomic_DNA.
DR EMBL; AB101804; BAC80393.1; -; Genomic_DNA.
DR EMBL; AB101805; BAC80394.1; -; Genomic_DNA.
DR EMBL; AB101806; BAC80395.1; -; Genomic_DNA.
DR EMBL; AB101807; BAC80396.1; -; Genomic_DNA.
DR EMBL; AB101808; BAC80397.1; -; Genomic_DNA.
DR EMBL; AB101809; BAC80398.1; -; Genomic_DNA.
DR EMBL; AB101810; BAC80399.1; -; Genomic_DNA.
DR EMBL; AB101811; BAC80400.1; -; Genomic_DNA.
DR EMBL; AB101812; BAC80401.1; -; Genomic_DNA.
DR EMBL; AB101813; BAC80402.1; -; Genomic_DNA.
DR EMBL; AB101814; BAC80403.1; -; Genomic_DNA.
DR EMBL; AB101815; BAC80404.1; -; Genomic_DNA.
DR EMBL; AB101816; BAC80405.1; -; Genomic_DNA.
DR EMBL; AB101817; BAC80406.1; -; Genomic_DNA.
DR EMBL; AB101818; BAC80407.1; -; Genomic_DNA.
DR EMBL; AB101819; BAC80408.1; -; Genomic_DNA.
DR EMBL; AB101820; BAC80409.1; -; Genomic_DNA.
DR EMBL; AB101831; BAC80420.1; -; Genomic_DNA.
DR EMBL; AB101832; BAC80421.1; -; Genomic_DNA.
DR EMBL; AB101833; BAC80422.1; -; Genomic_DNA.
DR EMBL; AB101834; BAC80423.1; -; Genomic_DNA.
DR EMBL; AB101835; BAC80424.1; -; Genomic_DNA.
DR EMBL; AB101836; BAC80425.1; -; Genomic_DNA.
DR EMBL; AB101837; BAC80426.1; -; Genomic_DNA.
DR EMBL; AB101838; BAC80427.1; -; Genomic_DNA.
DR EMBL; AB101839; BAC80428.1; -; Genomic_DNA.
DR EMBL; AB101840; BAC80429.1; -; Genomic_DNA.
DR EMBL; AB101841; BAC80430.1; -; Genomic_DNA.
DR EMBL; AB101842; BAC80431.1; -; Genomic_DNA.
DR EMBL; AB101843; BAC80432.1; -; Genomic_DNA.
DR EMBL; AB101844; BAC80433.1; -; Genomic_DNA.
DR EMBL; AB101845; BAC80434.1; -; Genomic_DNA.
DR EMBL; AB101846; BAC80435.1; -; Genomic_DNA.
DR EMBL; AB101847; BAC80436.1; -; Genomic_DNA.
DR EMBL; AB101848; BAC80437.1; -; Genomic_DNA.
DR EMBL; AB101849; BAC80438.1; -; Genomic_DNA.
DR EMBL; AB101850; BAC80439.1; -; Genomic_DNA.
DR EMBL; AB102647; BAC81116.1; -; mRNA.
DR EMBL; CR542258; CAG47054.1; -; mRNA.
DR EMBL; CR542276; CAG47072.1; -; mRNA.
DR EMBL; BT019884; AAV38687.1; -; mRNA.
DR EMBL; BX936385; CAI95780.1; -; Genomic_DNA.
DR EMBL; CH471172; EAW72710.1; -; Genomic_DNA.
DR EMBL; BC000317; AAH00317.1; -; mRNA.
DR EMBL; BC012201; AAH12201.1; -; mRNA.
DR EMBL; U14623; AAA21558.1; -; Genomic_DNA.
DR EMBL; L05086; AAC15851.1; -; mRNA.
DR PIR; I37082; I37082.
DR RefSeq; NP_001484.1; NM_001493.2.
DR UniGene; Hs.595950; -.
DR UniGene; Hs.74576; -.
DR ProteinModelPortal; P31150; -.
DR SMR; P31150; 1-430.
DR IntAct; P31150; 11.
DR MINT; MINT-2859157; -.
DR STRING; 9606.ENSP00000394071; -.
DR PhosphoSite; P31150; -.
DR DMDM; 1707886; -.
DR OGP; P31150; -.
DR REPRODUCTION-2DPAGE; IPI00010154; -.
DR UCD-2DPAGE; P31150; -.
DR PaxDb; P31150; -.
DR PeptideAtlas; P31150; -.
DR PRIDE; P31150; -.
DR DNASU; 2664; -.
DR Ensembl; ENST00000447750; ENSP00000394071; ENSG00000203879.
DR Ensembl; ENST00000601899; ENSP00000471186; ENSG00000268690.
DR GeneID; 2664; -.
DR KEGG; hsa:2664; -.
DR UCSC; uc004fli.4; human.
DR CTD; 2664; -.
DR GeneCards; GC0XP153665; -.
DR H-InvDB; HIX0056464; -.
DR HGNC; HGNC:4226; GDI1.
DR HPA; CAB012979; -.
DR HPA; HPA049290; -.
DR MIM; 300104; gene.
DR MIM; 300849; phenotype.
DR neXtProt; NX_P31150; -.
DR Orphanet; 777; X-linked non-syndromic intellectual deficit.
DR PharmGKB; PA28641; -.
DR eggNOG; COG5044; -.
DR HOVERGEN; HBG000839; -.
DR InParanoid; P31150; -.
DR KO; K17255; -.
DR OMA; FGLDKNT; -.
DR Reactome; REACT_111102; Signal Transduction.
DR ChiTaRS; GDI1; human.
DR GeneWiki; GDI1; -.
DR GenomeRNAi; 2664; -.
DR NextBio; 10512; -.
DR PRO; PR:P31150; -.
DR ArrayExpress; P31150; -.
DR Bgee; P31150; -.
DR CleanEx; HS_GDI1; -.
DR Genevestigator; P31150; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR GO; GO:0005092; F:GDP-dissociation inhibitor activity; TAS:ProtInc.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0005093; F:Rab GDP-dissociation inhibitor activity; IEA:Ensembl.
DR GO; GO:0050771; P:negative regulation of axonogenesis; ISS:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:GOC.
DR GO; GO:0015031; P:protein transport; IEA:InterPro.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome.
DR InterPro; IPR018203; GDP_dissociation_inhibitor.
DR InterPro; IPR000806; RabGDI.
DR Pfam; PF00996; GDI; 1.
DR PRINTS; PR00892; RABGDI.
DR PRINTS; PR00891; RABGDIREP.
PE 1: Evidence at protein level;
KW Complete proteome; Cytoplasm; Direct protein sequencing;
KW Disease mutation; GTPase activation; Mental retardation;
KW Reference proteome.
FT CHAIN 1 447 Rab GDP dissociation inhibitor alpha.
FT /FTId=PRO_0000056671.
FT VARIANT 92 92 L -> P (in MRX41; causes reduced binding
FT and recycling of RAB3A).
FT /FTId=VAR_008130.
FT VARIANT 423 423 R -> P (in MRX41).
FT /FTId=VAR_008131.
FT CONFLICT 34 34 D -> G (in Ref. 2; BAA08078).
FT CONFLICT 36 36 N -> K (in Ref. 2; BAA08078).
FT CONFLICT 149 151 NFD -> GTY (in Ref. 2; BAA08078).
FT CONFLICT 347 347 G -> V (in Ref. 13; AAC15851).
FT CONFLICT 409 409 H -> Q (in Ref. 13; AAC15851).
FT CONFLICT 416 416 D -> G (in Ref. 13; AAC15851).
FT CONFLICT 442 442 F -> S (in Ref. 2; BAA08078).
SQ SEQUENCE 447 AA; 50583 MW; BC283A445E50A652 CRC64;
MDEEYDVIVL GTGLTECILS GIMSVNGKKV LHMDRNPYYG GESSSITPLE ELYKRFQLLE
GPPESMGRGR DWNVDLIPKF LMANGQLVKM LLYTEVTRYL DFKVVEGSFV YKGGKIYKVP
STETEALASN LMGMFEKRRF RKFLVFVANF DENDPKTFEG VDPQTTSMRD VYRKFDLGQD
VIDFTGHALA LYRTDDYLDQ PCLETVNRIK LYSESLARYG KSPYLYPLYG LGELPQGFAR
LSAIYGGTYM LNKPVDDIIM ENGKVVGVKS EGEVARCKQL ICDPSYIPDR VRKAGQVIRI
ICILSHPIKN TNDANSCQII IPQNQVNRKS DIYVCMISYA HNVAAQGKYI AIASTTVETT
DPEKEVEPAL ELLEPIDQKF VAISDLYEPI DDGCESQVFC SCSYDATTHF ETTCNDIKDI
YKRMAGTAFD FENMKRKQND VFGEAEQ
//
MIM
300104
*RECORD*
*FIELD* NO
300104
*FIELD* TI
*300104 GDP DISSOCIATION INHIBITOR 1; GDI1
;;RAB GDP-DISSOCIATION INHIBITOR, ALPHA; RABGDIA;;
read moreRAB GDI-ALPHA;;
RHOGDI;;
OLIGOPHRENIN 2; OPHN2
*FIELD* TX
DESCRIPTION
The GDP dissociation inhibitor-1 gene (GDI1) regulates the GDP-GTP
exchange reaction of members of the rab family, small GTP-binding
proteins of the ras superfamily, that are involved in vesicular
trafficking of molecules between cellular organelles. The rab proteins
undergo activation upon GTP binding, and GTP hydrolysis to GDP
inactivates the protein. GDI proteins slow the rate of dissociation of
GDP from rab proteins and release GDP from membrane-bound rabs (Bachner
et al., 1995).
Chelly (1999) referred to the protein as oligophrenin-2 (OPHN2).
CLONING
Matsui et al. (1990) cloned a bovine GDI gene, designated smg p25A,
using an oligomer probe based on partial amino acid sequence. The
447-amino acid protein was expressed in E. coli and shown to have GDI
activity. Sedlacek et al. (1994) noted 2 rat rab GDI sequences,
designated alpha and beta, in the EMBL database (accession nos. X74401
and X74402).
Sedlacek et al. (1993) characterized a human rab GDI1 locus, which they
called XAP-4. The predicted amino acid sequence of the protein is 98.4%
identical to the bovine and rat GDI-alphas and 86.5% identical to human
rab GDI-beta (GDI2; 600767). The rab GDI-alpha gene was expressed at
highest levels as a 2.5-kb mRNA in brain, with lesser amounts in the
muscle and kidney. Subsequent work by Bachner et al. (1995) showed
expression predominantly in neural and sensory tissues.
D'Adamo et al. (1997) noted that GDI is expressed in all parts of the
adult brain and, by in situ hybridization analysis, it is detectable in
post-mitotic neural cells during mouse development, with the same timing
and in the same cell types as Rab3a.
Shisheva et al. (1994) cloned and characterized the mouse gene.
GENE FUNCTION
Rab GTPases regulate vesicle trafficking in eukaryotic cells by
reversibly associating with lipid membranes. Inactive Rab GTPases are
maintained in the cytosol by binding to GDP-dissociation inhibitor. It
is believed that specialized proteins are required to displace GDI from
Rab GTPases before Rab activation by GDP-GTP exchange factors (GEFs).
Machner and Isberg (2007) found that SidM from Legionella pneumophila
could act as both GEF and GDI-displacement factor (GDF) for Rab1
(179508). Rab1 released from GDI was inserted into liposomal membranes
and was used as a substrate for SidM-mediated nucleotide exchange.
During host cell infection, recruitment of Rab1 to Legionella-containing
vacuoles depended on the GDF activity of SidM. Thus, Machner and Isberg
(2007) concluded that GDF and GEF activity can be promoted by a single
protein, and GDF activity can coordinate Rab1 recruitment from the
GDI-bound pool.
GENE STRUCTURE
Sedlacek et al. (1994) characterized the human RABGDIA gene, which has
11 exons in a span of about 7 kb.
BIOCHEMICAL FEATURES
Hoffman et al. (2000) determined the 2.6-angstrom x-ray crystallographic
structure of the GTP-binding protein CDC42 (116952) in complex with
GDI1. The structure revealed 2 important sites of interaction between
GDI1 and CDC42. First, the N-terminal regulatory arm of GDI1 binds to
the switch I and II domains of CDC42, leading to inhibition of both GDP
dissociation and GTP hydrolysis. Second, the geranylgeranyl moiety of
CDC42 inserts into a hydrophobic pocket within the immunoglobulin-like
domain of the GDI1 molecule, leading to membrane release. The structural
data demonstrated how GDIs serve as negative regulators of small
GTP-binding proteins and how the isoprenoid moiety is utilized in this
critical regulatory interaction.
Rak et al. (2003) used a combination of chemical synthesis and protein
engineering to generate and crystallize the monoprenylated YPT1-RABGDI
complex. The structure of this complex was determined to 1.5-angstrom
resolution and provided a structural basis for the ability of RABGDI to
inhibit nucleotide release by RAB proteins. Isoprenoid binding requires
a conformational change that opens a cavity in the hydrophobic core of
its domain II. Analysis of the structure provided a molecular basis for
understanding a RABGDI mutant that causes mental retardation.
MAPPING
Sedlacek et al. (1993) localized a human rab GDI locus, which they
called XAP-4, near G6PD (305900) on chromosome Xq28. Sedlacek et al.
(1994) found that RABGDIA is present in a gene-dense region of Xq28 with
at least 8 other loci in the interval (approximately 220 kb) between QM
(RPL10; 312173) and G6PD.
MOLECULAR GENETICS
D'Adamo et al. (1997,1998) demonstrated unique mutations in the RABGDIA
gene in affected members of the MRX41 family (300104.0001) reported by
Hamel et al. (1996) and the MRX48 family (300104.0002) reported by des
Portes et al. (1997).
Bienvenu et al. (1998) carried out mutation screening of the whole
coding region of the GDI1 gene, using a combination of denaturing
gradient gel electrophoresis and direct sequencing, in 164 patients
found negative for expansions across the FRAXA GCC repeat (309550.0004).
The authors identified a novel missense mutation in exon 11 of the GDI1
gene (300104.0003) in a family with nonspecific mental retardation. In
this large French family, all affected males showed moderate to severe
mental retardation. X-linked semidominant inheritance was strongly
suggested by the severe phenotypes in males in comparison to mildly
affected females or unaffected obligate carriers. The study suggested
that the prevalence of GDI1 mutations in nonspecific mental retardation
may be 0.5 to 1%.
Vandewalle et al. (2009) demonstrated a novel X-linked mental
retardation syndrome due to recurrent copy number gain of Xq28
specifically involving the GDI1 gene. Tiling Xq28 region-specific oligo
array revealed that all aberrations started at the beginning of the low
copy repeat LCR-K1 at position 153.20 Mb and ended just distal to LCR-L2
at 153.54 Mb. The copy number gain always included 18 annotated genes,
of which RPL10 (312173), ATP6AP1 (300197), and GDI1 are highly expressed
in brain. Of these, Vandewalle et al. (2009) considered GDI1 the most
likely candidate. Its copy number correlated with the severity of
clinical features: it was duplicated in a family with nonsyndromic
moderate mental retardation, triplicated in males from 2 families with
mild mental retardation and additional features, and present in 5 copies
in a family with a severe syndromic form of mental retardation.
Expression analysis showed copy number-dependent increased mRNA levels
in affected patients compared to control individuals. Interestingly,
analysis of the breakpoint regions suggested a recombination mechanism
that involves 2 adjacent but different sets of low copy repeats.
EVOLUTION
Human evolution is characterized by a dramatic increase in brain size
and complexity. To probe its genetic basis, Dorus et al. (2004) examined
the evolution of genes involved in diverse aspects of nervous system
biology. These genes, including GDI1, displayed significantly higher
rates of protein evolution in primates than in rodents. This trend was
most pronounced for the subset of genes implicated in nervous system
development. Moreover, within primates, the acceleration of protein
evolution was most prominent in the lineage leading from ancestral
primates to humans. Dorus et al. (2004) concluded that the phenotypic
evolution of the human nervous system has a salient molecular correlate,
i.e., accelerated evolution of the underlying genes, particularly those
linked to nervous system development.
ANIMAL MODEL
D'Adamo et al. (2002) reported the cognitive and behavioral
characteristics of mice carrying a deletion of Gdi1. The Gdi1-deficient
mice were fertile and anatomically normal, and exhibited normal spatial
and episodic memory and emotional behavior. However, they were impaired
in tasks requiring formation of short-term temporal associations,
suggesting a defect in short-term memory. In addition, they showed
lowered aggression and altered social behavior. In mice, as in humans,
lack of Gdi1 spared most central nervous system functions and
preferentially impaired only a few forebrain functions required to form
temporal associations.
Using electron microscopy and electrophysiology, Bianchi et al. (2009)
reported that lack of Gdi1 in mice impaired several steps in synaptic
vesicle (SV) biogenesis and recycling in the hippocampus. Alteration of
the SV reserve pool and a 50% reduction in the total number of SVs in
adult synapses may be dependent on a defective endosomal-dependent
recycling and may lead to the observed alterations in short-term
plasticity. The short-term memory deficit in mutant mice, observed when
using fear-conditioning protocols with short intervals between trials,
disappeared when Gdi1-mutant mice were allowed to have longer intervals
between sessions. Deficits in radial maze learning could also be
corrected by providing less challenging pretraining. Bianchi et al.
(2009) hypothesized that an intact reserve pool of synaptic vesicles is
necessary for memory processing under challenging conditions in mice.
*FIELD* AV
.0001
MENTAL RETARDATION, X-LINKED 41
GDI1, LEU92PRO
In the family reported by Hamel et al. (1996) with X-linked nonspecific
mental retardation linked to Xq28 (MRX41; 300849), D'Adamo et al. (1997)
identified a T-to-C transition in the GDI1 cDNA, resulting in a
leu92-to-pro (L92P) substitution.
.0002
MENTAL RETARDATION, X-LINKED 41
GDI1, ARG70TER
In affected members of the MRX48 (300849) family reported by Des Portes
et al. (1997), D'Adamo et al. (1997) identified a 366C-T transition in
the GDI1 gene, resulting in an arg70-to-ter (R70X) substitution. D'Adamo
et al. (1998) speculated that the truncated message could lead to
synthesis of a peptide of 69 amino acids, which would likely be unstable
and degraded. Moderate to severe mental retardation was found in 7 males
and milder intellectual impairment in 2 females, without any specific
clinical, radiologic, or biologic features.
.0003
MENTAL RETARDATION, X-LINKED 41
GDI1, ARG423PRO
In affected members of a large French family with MRX48 (300849),
Bienvenu et al. (1998) identified a 1426G-C transversion in the GDI1
gene, resulting in an arg423-to-pro (R423P) substitution.
.0004
MENTAL RETARDATION, X-LINKED 41
GDI1, 2-BP DEL, 1185AG
In affected members of a multigenerational German family in which 9
males had nonsyndromic X-linked mental retardation (300849),
Strobl-Wildemann et al. (2011) identified a 2-bp deletion (1185delAG) in
exon 10 of the GDI1 gene, resulting in a frameshift and premature
termination. The proband was noted to have absence seizures at age 12, a
small pointed chin, and crowded teeth, but major dysmorphic features
were not present and no other patients had dysmorphic features. Two of 4
female carriers had learning disabilities, and 1 also had
attention-deficit disorder.
*FIELD* RF
1. Bachner, D.; Sedlacek, Z.; Korn, B.; Hameister, H.; Poustka, A.
: Expression patterns of two human genes coding for different rab
GDP-dissociation inhibitors (GDIs), extremely conserved proteins involved
in cellular transport. Hum. Molec. Genet. 4: 701-708, 1995.
2. Bianchi, V.; Farisello, P.; Baldelli, P.; Meskenaite, V.; Milanese,
M.; Vecellio, M.; Muhlemann, S.; Lipp, H. P.; Bonanno, G.; Benfenati,
F.; Toniolo, D.; D'Adamo, P.: Cognitive impairment in Gdi1-deficient
mice is associated with altered synaptic vesicle pools and short-term
synaptic plasticity, and can be corrected by appropriate learning
training. Hum. Molec. Genet. 18: 105-117, 2009.
3. Bienvenu, T.; des Portes, V.; Saint Martin, A.; McDonell, N.; Billuart,
P.; Carrie, A.; Vinet, M.-C.; Couvert, P.; Toniolo, D.; Ropers, H.-H.;
Moraine, C.; van Bokhoven, H.; Fryns, J.-P.; Kahn, A.; Beldjord, C.;
Chelly, J.: Non-specific X-linked semidominant mental retardation
by mutations in a Rab GDP-dissociation inhibitor. Hum. Molec. Genet. 7:
1311-1315, 1998.
4. Chelly, J.: Breakthroughs in molecular and cellular mechanisms
underlying X-linked mental retardation. Hum. Molec. Genet. 8: 1833-1838,
1999.
5. D'Adamo, P.; Gulisano, M.; Oostra, B. A.; Chelly, J.; Toniolo,
D.: GDI is responsible for X-linked mental retardation. (Abstract) Am.
J. Hum. Genet. 61 (suppl.): A11 only, 1997.
6. D'Adamo, P.; Menegon, A.; Lo Nigro, C.; Grasso, M.; Gulisano, M.;
Tamanini, F.; Bienvenu, T.; Gedeon, A. K.; Oostra, B.; Wu, S.-K.;
Tandon, A.; Valtorta, F.; Balch, W. E.; Chelly, J.; Toniolo, D.:
Mutations in GDI1 are responsible for X-linked non-specific mental
retardation. Nature Genet. 19: 134-139, 1998. Note: Erratum: Nature
Genet. 19: 303 only, 1998.
7. D'Adamo, P.; Welzl, H.; Papadimitriou, S.; di Barletta, M. R.;
Tiveron, C.; Tatangelo, L.; Pozzi, L.; Chapman, P. F.; Knevett, S.
G.; Ramsay, M. F.; Valtorta, F.; Leoni, C.; Menegon, A.; Wolfer, D.
P.; Lipp, H.-P.; Toniolo, D.: Deletion of the mental retardation
gene Gdi1 impairs associative memory and alters social behavior in
mice. Hum. Molec. Genet. 11: 2567-2580, 2002.
8. Des Portes, V.; Billuart, P.; Carrie, A.; Bachner, L.; Bienvenu,
T.; Vinet, M. C.; Beldjord, C.; Ponsot, G.; Kahn, A.; Boue, J.; Chelly,
J.: A gene for dominant nonspecific X-linked mental retardation is
located in Xq28. Am. J. Hum. Genet. 60: 903-909, 1997.
9. Dorus, S.; Vallender, E. J.; Evans, P. D.; Anderson, J. R.; Gilbert,
S. L.; Mahowald, M.; Wyckoff, G. J.; Malcom, C. M.; Lahn, B. T.:
Accelerated evolution of nervous system genes in the origin of Homo
sapiens. Cell 119: 1027-1040, 2004.
10. Hamel, B. C. J.; Kremer, H.; Wesby-van Swaay, E.; van den Helm,
B.; Smits, A. P. T.; Oostra, B. A.; Ropers, H.-H.; Mariman, E. C.
M.: A gene for nonspecific X-linked mental retardation (MRX41) is
located in the distal segment of Xq28. Am. J. Med. Genet. 64: 131-133,
1996.
11. Hoffman, G. R.; Nassar, N.; Cerione, R. A.: Structure of the
Rho family GTP-binding protein Cdc42 in complex with the multifunctional
regulator RhoGDI. Cell 100: 345-356, 2000.
12. Machner, M. P.; Isberg, R. R.: A bifunctional bacterial protein
links GDI displacement to Rab1 activation. Science 318: 974-977,
2007.
13. Matsui, Y.; Kikuchi, A.; Araki, S.; Hata, Y.; Kondo, J.; Teranishi,
Y.; Takai, Y.: Molecular cloning and characterization of a novel
type of regulatory protein (GDI) for smg p25A, a ras p21-like GTP-binding
protein. Molec. Cell. Biol. 10: 4116-4122, 1990.
14. Rak, A.; Pylypenko, O.; Durek, T.; Watzke, A.; Kushnir, S.; Brunsveld,
L.; Waldmann, H.; Goody, R. S.; Alexandrov, K.: Structure of Rab
GDP-dissociation inhibitor in complex with prenylated YPT1 GTPase. Science 302:
646-650, 2003.
15. Sedlacek, Z.; Konecki, D. S.; Korn, B.; Klauck, S. M.; Poustka,
A.: Evolutionary conservation and genomic organization of XAP-4,
an Xq28 located gene coding for a human rab GDP-dissociation inhibitor
(GDI). Mammalian Genome 5: 633-639, 1994.
16. Sedlacek, Z.; Korn, B.; Konecki, D. S.; Siebenhaar, R.; Coy, J.
F.; Kioschis, P.; Poustka, A.: Construction of a transcription map
of a 300 kb region around the human G6PD locus by direct cDNA selection. Hum.
Molec. Genet. 2: 1865-1869, 1993.
17. Shisheva, A.; Sudhof, T. C.; Czech, M. P.: Cloning, characterization,
and expression of a novel GDP dissociation inhibitor isoform from
skeletal muscle. Molec. Cell. Biol. 14: 3459-3468, 1994.
18. Strobl-Wildemann, G.; Kalscheuer, V. M.; Hu, H.; Wrogemann, K.;
Ropers, H.-H.; Tzschach, A.: Novel GDI1 mutation in a large family
with nonsyndromic X-linked intellectual disability. Am. J. Med. Genet. 155A:
3067-3070, 2011.
19. Vandewalle, J.; Van Esch, H.; Govaerts, K.; Verbeeck, J.; Zweir,
C.; Madrigal, I.; Mila, M.; Pijkels, E.; Fernandez, I.; Kohlase, J.;
Spaich, C.; Rauch, A.; Fryns, J.-P.; Marynen, P.; Froyen, G.: Dosage-dependent
severity of the phenotype in patients with mental retardation due
to a recurrent copy-number gain at Xq28 mediated by an unusual recombination. Am.
J. Hum. Genet. 85: 809-822, 2009.
*FIELD* CN
Cassandra L. Kniffin - updated: 12/22/2011
Ada Hamosh - updated: 3/16/2010
George E. Tiller - updated: 10/23/2009
Ada Hamosh - updated: 11/26/2007
Stylianos E. Antonarakis - updated: 1/10/2005
George E. Tiller - updated: 2/3/2004
Ada Hamosh - updated: 11/11/2003
Stylianos E. Antonarakis - updated: 4/5/2000
Victor A. McKusick - updated: 10/12/1999
Victor A. McKusick - updated: 5/7/1999
Victor A. McKusick - updated: 11/3/1998
Victor A. McKusick - updated: 5/27/1998
Victor A. McKusick - updated: 10/24/1997
*FIELD* CD
Alan F. Scott: 9/11/1995
*FIELD* ED
carol: 09/12/2013
carol: 12/22/2011
ckniffin: 12/22/2011
carol: 8/1/2011
terry: 9/16/2010
terry: 4/1/2010
alopez: 3/18/2010
terry: 3/16/2010
wwang: 11/3/2009
terry: 10/23/2009
wwang: 11/25/2008
ckniffin: 11/17/2008
alopez: 11/28/2007
terry: 11/26/2007
carol: 9/10/2007
ckniffin: 9/10/2007
carol: 2/17/2006
mgross: 1/10/2005
carol: 3/17/2004
cwells: 2/3/2004
tkritzer: 11/12/2003
terry: 11/11/2003
carol: 11/7/2003
ckniffin: 11/7/2003
alopez: 10/18/2002
mgross: 4/5/2000
carol: 10/12/1999
kayiaros: 7/12/1999
mgross: 5/17/1999
mgross: 5/12/1999
terry: 5/7/1999
carol: 11/9/1998
terry: 11/3/1998
carol: 8/25/1998
carol: 7/1/1998
alopez: 6/1/1998
terry: 5/27/1998
mark: 11/14/1997
mark: 10/28/1997
mark: 10/27/1997
mark: 10/25/1997
*RECORD*
*FIELD* NO
300104
*FIELD* TI
*300104 GDP DISSOCIATION INHIBITOR 1; GDI1
;;RAB GDP-DISSOCIATION INHIBITOR, ALPHA; RABGDIA;;
read moreRAB GDI-ALPHA;;
RHOGDI;;
OLIGOPHRENIN 2; OPHN2
*FIELD* TX
DESCRIPTION
The GDP dissociation inhibitor-1 gene (GDI1) regulates the GDP-GTP
exchange reaction of members of the rab family, small GTP-binding
proteins of the ras superfamily, that are involved in vesicular
trafficking of molecules between cellular organelles. The rab proteins
undergo activation upon GTP binding, and GTP hydrolysis to GDP
inactivates the protein. GDI proteins slow the rate of dissociation of
GDP from rab proteins and release GDP from membrane-bound rabs (Bachner
et al., 1995).
Chelly (1999) referred to the protein as oligophrenin-2 (OPHN2).
CLONING
Matsui et al. (1990) cloned a bovine GDI gene, designated smg p25A,
using an oligomer probe based on partial amino acid sequence. The
447-amino acid protein was expressed in E. coli and shown to have GDI
activity. Sedlacek et al. (1994) noted 2 rat rab GDI sequences,
designated alpha and beta, in the EMBL database (accession nos. X74401
and X74402).
Sedlacek et al. (1993) characterized a human rab GDI1 locus, which they
called XAP-4. The predicted amino acid sequence of the protein is 98.4%
identical to the bovine and rat GDI-alphas and 86.5% identical to human
rab GDI-beta (GDI2; 600767). The rab GDI-alpha gene was expressed at
highest levels as a 2.5-kb mRNA in brain, with lesser amounts in the
muscle and kidney. Subsequent work by Bachner et al. (1995) showed
expression predominantly in neural and sensory tissues.
D'Adamo et al. (1997) noted that GDI is expressed in all parts of the
adult brain and, by in situ hybridization analysis, it is detectable in
post-mitotic neural cells during mouse development, with the same timing
and in the same cell types as Rab3a.
Shisheva et al. (1994) cloned and characterized the mouse gene.
GENE FUNCTION
Rab GTPases regulate vesicle trafficking in eukaryotic cells by
reversibly associating with lipid membranes. Inactive Rab GTPases are
maintained in the cytosol by binding to GDP-dissociation inhibitor. It
is believed that specialized proteins are required to displace GDI from
Rab GTPases before Rab activation by GDP-GTP exchange factors (GEFs).
Machner and Isberg (2007) found that SidM from Legionella pneumophila
could act as both GEF and GDI-displacement factor (GDF) for Rab1
(179508). Rab1 released from GDI was inserted into liposomal membranes
and was used as a substrate for SidM-mediated nucleotide exchange.
During host cell infection, recruitment of Rab1 to Legionella-containing
vacuoles depended on the GDF activity of SidM. Thus, Machner and Isberg
(2007) concluded that GDF and GEF activity can be promoted by a single
protein, and GDF activity can coordinate Rab1 recruitment from the
GDI-bound pool.
GENE STRUCTURE
Sedlacek et al. (1994) characterized the human RABGDIA gene, which has
11 exons in a span of about 7 kb.
BIOCHEMICAL FEATURES
Hoffman et al. (2000) determined the 2.6-angstrom x-ray crystallographic
structure of the GTP-binding protein CDC42 (116952) in complex with
GDI1. The structure revealed 2 important sites of interaction between
GDI1 and CDC42. First, the N-terminal regulatory arm of GDI1 binds to
the switch I and II domains of CDC42, leading to inhibition of both GDP
dissociation and GTP hydrolysis. Second, the geranylgeranyl moiety of
CDC42 inserts into a hydrophobic pocket within the immunoglobulin-like
domain of the GDI1 molecule, leading to membrane release. The structural
data demonstrated how GDIs serve as negative regulators of small
GTP-binding proteins and how the isoprenoid moiety is utilized in this
critical regulatory interaction.
Rak et al. (2003) used a combination of chemical synthesis and protein
engineering to generate and crystallize the monoprenylated YPT1-RABGDI
complex. The structure of this complex was determined to 1.5-angstrom
resolution and provided a structural basis for the ability of RABGDI to
inhibit nucleotide release by RAB proteins. Isoprenoid binding requires
a conformational change that opens a cavity in the hydrophobic core of
its domain II. Analysis of the structure provided a molecular basis for
understanding a RABGDI mutant that causes mental retardation.
MAPPING
Sedlacek et al. (1993) localized a human rab GDI locus, which they
called XAP-4, near G6PD (305900) on chromosome Xq28. Sedlacek et al.
(1994) found that RABGDIA is present in a gene-dense region of Xq28 with
at least 8 other loci in the interval (approximately 220 kb) between QM
(RPL10; 312173) and G6PD.
MOLECULAR GENETICS
D'Adamo et al. (1997,1998) demonstrated unique mutations in the RABGDIA
gene in affected members of the MRX41 family (300104.0001) reported by
Hamel et al. (1996) and the MRX48 family (300104.0002) reported by des
Portes et al. (1997).
Bienvenu et al. (1998) carried out mutation screening of the whole
coding region of the GDI1 gene, using a combination of denaturing
gradient gel electrophoresis and direct sequencing, in 164 patients
found negative for expansions across the FRAXA GCC repeat (309550.0004).
The authors identified a novel missense mutation in exon 11 of the GDI1
gene (300104.0003) in a family with nonspecific mental retardation. In
this large French family, all affected males showed moderate to severe
mental retardation. X-linked semidominant inheritance was strongly
suggested by the severe phenotypes in males in comparison to mildly
affected females or unaffected obligate carriers. The study suggested
that the prevalence of GDI1 mutations in nonspecific mental retardation
may be 0.5 to 1%.
Vandewalle et al. (2009) demonstrated a novel X-linked mental
retardation syndrome due to recurrent copy number gain of Xq28
specifically involving the GDI1 gene. Tiling Xq28 region-specific oligo
array revealed that all aberrations started at the beginning of the low
copy repeat LCR-K1 at position 153.20 Mb and ended just distal to LCR-L2
at 153.54 Mb. The copy number gain always included 18 annotated genes,
of which RPL10 (312173), ATP6AP1 (300197), and GDI1 are highly expressed
in brain. Of these, Vandewalle et al. (2009) considered GDI1 the most
likely candidate. Its copy number correlated with the severity of
clinical features: it was duplicated in a family with nonsyndromic
moderate mental retardation, triplicated in males from 2 families with
mild mental retardation and additional features, and present in 5 copies
in a family with a severe syndromic form of mental retardation.
Expression analysis showed copy number-dependent increased mRNA levels
in affected patients compared to control individuals. Interestingly,
analysis of the breakpoint regions suggested a recombination mechanism
that involves 2 adjacent but different sets of low copy repeats.
EVOLUTION
Human evolution is characterized by a dramatic increase in brain size
and complexity. To probe its genetic basis, Dorus et al. (2004) examined
the evolution of genes involved in diverse aspects of nervous system
biology. These genes, including GDI1, displayed significantly higher
rates of protein evolution in primates than in rodents. This trend was
most pronounced for the subset of genes implicated in nervous system
development. Moreover, within primates, the acceleration of protein
evolution was most prominent in the lineage leading from ancestral
primates to humans. Dorus et al. (2004) concluded that the phenotypic
evolution of the human nervous system has a salient molecular correlate,
i.e., accelerated evolution of the underlying genes, particularly those
linked to nervous system development.
ANIMAL MODEL
D'Adamo et al. (2002) reported the cognitive and behavioral
characteristics of mice carrying a deletion of Gdi1. The Gdi1-deficient
mice were fertile and anatomically normal, and exhibited normal spatial
and episodic memory and emotional behavior. However, they were impaired
in tasks requiring formation of short-term temporal associations,
suggesting a defect in short-term memory. In addition, they showed
lowered aggression and altered social behavior. In mice, as in humans,
lack of Gdi1 spared most central nervous system functions and
preferentially impaired only a few forebrain functions required to form
temporal associations.
Using electron microscopy and electrophysiology, Bianchi et al. (2009)
reported that lack of Gdi1 in mice impaired several steps in synaptic
vesicle (SV) biogenesis and recycling in the hippocampus. Alteration of
the SV reserve pool and a 50% reduction in the total number of SVs in
adult synapses may be dependent on a defective endosomal-dependent
recycling and may lead to the observed alterations in short-term
plasticity. The short-term memory deficit in mutant mice, observed when
using fear-conditioning protocols with short intervals between trials,
disappeared when Gdi1-mutant mice were allowed to have longer intervals
between sessions. Deficits in radial maze learning could also be
corrected by providing less challenging pretraining. Bianchi et al.
(2009) hypothesized that an intact reserve pool of synaptic vesicles is
necessary for memory processing under challenging conditions in mice.
*FIELD* AV
.0001
MENTAL RETARDATION, X-LINKED 41
GDI1, LEU92PRO
In the family reported by Hamel et al. (1996) with X-linked nonspecific
mental retardation linked to Xq28 (MRX41; 300849), D'Adamo et al. (1997)
identified a T-to-C transition in the GDI1 cDNA, resulting in a
leu92-to-pro (L92P) substitution.
.0002
MENTAL RETARDATION, X-LINKED 41
GDI1, ARG70TER
In affected members of the MRX48 (300849) family reported by Des Portes
et al. (1997), D'Adamo et al. (1997) identified a 366C-T transition in
the GDI1 gene, resulting in an arg70-to-ter (R70X) substitution. D'Adamo
et al. (1998) speculated that the truncated message could lead to
synthesis of a peptide of 69 amino acids, which would likely be unstable
and degraded. Moderate to severe mental retardation was found in 7 males
and milder intellectual impairment in 2 females, without any specific
clinical, radiologic, or biologic features.
.0003
MENTAL RETARDATION, X-LINKED 41
GDI1, ARG423PRO
In affected members of a large French family with MRX48 (300849),
Bienvenu et al. (1998) identified a 1426G-C transversion in the GDI1
gene, resulting in an arg423-to-pro (R423P) substitution.
.0004
MENTAL RETARDATION, X-LINKED 41
GDI1, 2-BP DEL, 1185AG
In affected members of a multigenerational German family in which 9
males had nonsyndromic X-linked mental retardation (300849),
Strobl-Wildemann et al. (2011) identified a 2-bp deletion (1185delAG) in
exon 10 of the GDI1 gene, resulting in a frameshift and premature
termination. The proband was noted to have absence seizures at age 12, a
small pointed chin, and crowded teeth, but major dysmorphic features
were not present and no other patients had dysmorphic features. Two of 4
female carriers had learning disabilities, and 1 also had
attention-deficit disorder.
*FIELD* RF
1. Bachner, D.; Sedlacek, Z.; Korn, B.; Hameister, H.; Poustka, A.
: Expression patterns of two human genes coding for different rab
GDP-dissociation inhibitors (GDIs), extremely conserved proteins involved
in cellular transport. Hum. Molec. Genet. 4: 701-708, 1995.
2. Bianchi, V.; Farisello, P.; Baldelli, P.; Meskenaite, V.; Milanese,
M.; Vecellio, M.; Muhlemann, S.; Lipp, H. P.; Bonanno, G.; Benfenati,
F.; Toniolo, D.; D'Adamo, P.: Cognitive impairment in Gdi1-deficient
mice is associated with altered synaptic vesicle pools and short-term
synaptic plasticity, and can be corrected by appropriate learning
training. Hum. Molec. Genet. 18: 105-117, 2009.
3. Bienvenu, T.; des Portes, V.; Saint Martin, A.; McDonell, N.; Billuart,
P.; Carrie, A.; Vinet, M.-C.; Couvert, P.; Toniolo, D.; Ropers, H.-H.;
Moraine, C.; van Bokhoven, H.; Fryns, J.-P.; Kahn, A.; Beldjord, C.;
Chelly, J.: Non-specific X-linked semidominant mental retardation
by mutations in a Rab GDP-dissociation inhibitor. Hum. Molec. Genet. 7:
1311-1315, 1998.
4. Chelly, J.: Breakthroughs in molecular and cellular mechanisms
underlying X-linked mental retardation. Hum. Molec. Genet. 8: 1833-1838,
1999.
5. D'Adamo, P.; Gulisano, M.; Oostra, B. A.; Chelly, J.; Toniolo,
D.: GDI is responsible for X-linked mental retardation. (Abstract) Am.
J. Hum. Genet. 61 (suppl.): A11 only, 1997.
6. D'Adamo, P.; Menegon, A.; Lo Nigro, C.; Grasso, M.; Gulisano, M.;
Tamanini, F.; Bienvenu, T.; Gedeon, A. K.; Oostra, B.; Wu, S.-K.;
Tandon, A.; Valtorta, F.; Balch, W. E.; Chelly, J.; Toniolo, D.:
Mutations in GDI1 are responsible for X-linked non-specific mental
retardation. Nature Genet. 19: 134-139, 1998. Note: Erratum: Nature
Genet. 19: 303 only, 1998.
7. D'Adamo, P.; Welzl, H.; Papadimitriou, S.; di Barletta, M. R.;
Tiveron, C.; Tatangelo, L.; Pozzi, L.; Chapman, P. F.; Knevett, S.
G.; Ramsay, M. F.; Valtorta, F.; Leoni, C.; Menegon, A.; Wolfer, D.
P.; Lipp, H.-P.; Toniolo, D.: Deletion of the mental retardation
gene Gdi1 impairs associative memory and alters social behavior in
mice. Hum. Molec. Genet. 11: 2567-2580, 2002.
8. Des Portes, V.; Billuart, P.; Carrie, A.; Bachner, L.; Bienvenu,
T.; Vinet, M. C.; Beldjord, C.; Ponsot, G.; Kahn, A.; Boue, J.; Chelly,
J.: A gene for dominant nonspecific X-linked mental retardation is
located in Xq28. Am. J. Hum. Genet. 60: 903-909, 1997.
9. Dorus, S.; Vallender, E. J.; Evans, P. D.; Anderson, J. R.; Gilbert,
S. L.; Mahowald, M.; Wyckoff, G. J.; Malcom, C. M.; Lahn, B. T.:
Accelerated evolution of nervous system genes in the origin of Homo
sapiens. Cell 119: 1027-1040, 2004.
10. Hamel, B. C. J.; Kremer, H.; Wesby-van Swaay, E.; van den Helm,
B.; Smits, A. P. T.; Oostra, B. A.; Ropers, H.-H.; Mariman, E. C.
M.: A gene for nonspecific X-linked mental retardation (MRX41) is
located in the distal segment of Xq28. Am. J. Med. Genet. 64: 131-133,
1996.
11. Hoffman, G. R.; Nassar, N.; Cerione, R. A.: Structure of the
Rho family GTP-binding protein Cdc42 in complex with the multifunctional
regulator RhoGDI. Cell 100: 345-356, 2000.
12. Machner, M. P.; Isberg, R. R.: A bifunctional bacterial protein
links GDI displacement to Rab1 activation. Science 318: 974-977,
2007.
13. Matsui, Y.; Kikuchi, A.; Araki, S.; Hata, Y.; Kondo, J.; Teranishi,
Y.; Takai, Y.: Molecular cloning and characterization of a novel
type of regulatory protein (GDI) for smg p25A, a ras p21-like GTP-binding
protein. Molec. Cell. Biol. 10: 4116-4122, 1990.
14. Rak, A.; Pylypenko, O.; Durek, T.; Watzke, A.; Kushnir, S.; Brunsveld,
L.; Waldmann, H.; Goody, R. S.; Alexandrov, K.: Structure of Rab
GDP-dissociation inhibitor in complex with prenylated YPT1 GTPase. Science 302:
646-650, 2003.
15. Sedlacek, Z.; Konecki, D. S.; Korn, B.; Klauck, S. M.; Poustka,
A.: Evolutionary conservation and genomic organization of XAP-4,
an Xq28 located gene coding for a human rab GDP-dissociation inhibitor
(GDI). Mammalian Genome 5: 633-639, 1994.
16. Sedlacek, Z.; Korn, B.; Konecki, D. S.; Siebenhaar, R.; Coy, J.
F.; Kioschis, P.; Poustka, A.: Construction of a transcription map
of a 300 kb region around the human G6PD locus by direct cDNA selection. Hum.
Molec. Genet. 2: 1865-1869, 1993.
17. Shisheva, A.; Sudhof, T. C.; Czech, M. P.: Cloning, characterization,
and expression of a novel GDP dissociation inhibitor isoform from
skeletal muscle. Molec. Cell. Biol. 14: 3459-3468, 1994.
18. Strobl-Wildemann, G.; Kalscheuer, V. M.; Hu, H.; Wrogemann, K.;
Ropers, H.-H.; Tzschach, A.: Novel GDI1 mutation in a large family
with nonsyndromic X-linked intellectual disability. Am. J. Med. Genet. 155A:
3067-3070, 2011.
19. Vandewalle, J.; Van Esch, H.; Govaerts, K.; Verbeeck, J.; Zweir,
C.; Madrigal, I.; Mila, M.; Pijkels, E.; Fernandez, I.; Kohlase, J.;
Spaich, C.; Rauch, A.; Fryns, J.-P.; Marynen, P.; Froyen, G.: Dosage-dependent
severity of the phenotype in patients with mental retardation due
to a recurrent copy-number gain at Xq28 mediated by an unusual recombination. Am.
J. Hum. Genet. 85: 809-822, 2009.
*FIELD* CN
Cassandra L. Kniffin - updated: 12/22/2011
Ada Hamosh - updated: 3/16/2010
George E. Tiller - updated: 10/23/2009
Ada Hamosh - updated: 11/26/2007
Stylianos E. Antonarakis - updated: 1/10/2005
George E. Tiller - updated: 2/3/2004
Ada Hamosh - updated: 11/11/2003
Stylianos E. Antonarakis - updated: 4/5/2000
Victor A. McKusick - updated: 10/12/1999
Victor A. McKusick - updated: 5/7/1999
Victor A. McKusick - updated: 11/3/1998
Victor A. McKusick - updated: 5/27/1998
Victor A. McKusick - updated: 10/24/1997
*FIELD* CD
Alan F. Scott: 9/11/1995
*FIELD* ED
carol: 09/12/2013
carol: 12/22/2011
ckniffin: 12/22/2011
carol: 8/1/2011
terry: 9/16/2010
terry: 4/1/2010
alopez: 3/18/2010
terry: 3/16/2010
wwang: 11/3/2009
terry: 10/23/2009
wwang: 11/25/2008
ckniffin: 11/17/2008
alopez: 11/28/2007
terry: 11/26/2007
carol: 9/10/2007
ckniffin: 9/10/2007
carol: 2/17/2006
mgross: 1/10/2005
carol: 3/17/2004
cwells: 2/3/2004
tkritzer: 11/12/2003
terry: 11/11/2003
carol: 11/7/2003
ckniffin: 11/7/2003
alopez: 10/18/2002
mgross: 4/5/2000
carol: 10/12/1999
kayiaros: 7/12/1999
mgross: 5/17/1999
mgross: 5/12/1999
terry: 5/7/1999
carol: 11/9/1998
terry: 11/3/1998
carol: 8/25/1998
carol: 7/1/1998
alopez: 6/1/1998
terry: 5/27/1998
mark: 11/14/1997
mark: 10/28/1997
mark: 10/27/1997
mark: 10/25/1997
MIM
300849
*RECORD*
*FIELD* NO
300849
*FIELD* TI
#300849 MENTAL RETARDATION, X-LINKED 41; MRX41
;;MENTAL RETARDATION, X-LINKED 48; MRX48
read more*FIELD* TX
A number sign (#) is used with this entry because this form of X-linked
mental retardation, referred to as MRX41 or MRX48, is caused by mutation
in the GDI1 gene (300104) on chromosome Xq28.
CLINICAL FEATURES
Hamel et al. (1996) reported a family segregating mild to moderate
mental retardation as an X-linked trait (MRX41).
Des Portes et al. (1997) reported a large 3-generation family
segregating nonspecific X-linked mental retardation (MRX48). The
pedigree suggested X-linked semidominant inheritance: moderate to severe
mental retardation was found in 7 males and milder intellectual
impairment in 2 females, without any specific clinical, radiologic, or
biologic features.
Bienvenu et al. (1998) reported a large French family (family R) in
which all affected males showed moderate to severe mental retardation.
X-linked semidominant inheritance was strongly suggested by the severe
phenotypes in males in comparison to mildly affected females or
unaffected obligate carriers. The study suggested that the prevalence of
GDI1 mutations in nonspecific mental retardation may be 0.5 to 1%.
Strobl-Wildemann et al. (2011) reported a multigenerational German
family in which 9 males had nonsyndromic X-linked mental retardation.
The proband was noted to have absence seizures at age 12, a small
pointed chin, and crowded teeth, but no other dysmorphic features were
noted and no other patients had dysmorphic features. Two of 4 female
carriers had learning disabilities, and 1 also had attention-deficit
disorder. Strobl-Wildemann et al. (2011) noted the lack of specific
features that could alert the clinician to this form of mental
retardation.
MAPPING
By 2-point linkage analysis in a family segregating nonspecific X-linked
mental retardation (MRX41), Hamel et al. (1996) demonstrated linkage of
the disorder to marker DXS3 at Xq21.33 with a lod score of 2.56 at theta
= 0.0 and marker DXS1108 at Xq28 with a lod score of 3.82 at theta =
0.0. Multipoint linkage analysis showed that the odds for a location of
the locus at Xq28 versus Xq21.33 were 100:1.
In a large 3-generation French family segregating nonspecific X-linked
mental retardation (MRX48), des Portes et al. (1997) found linkage of
the disorder to DXS1684 with a maximum lod of 3.0 at theta = 0.0. The
authors commented that the mapping overlapped with that of MRX3 (309541)
and 4 other X-linked mental retardation families: MRX16 (300055); MRX25,
reported by Nordstrom et al. (1992); MRX28, reported by Holinski-Feder
et al. (1996); and MRX41, reported by Hamel et al. (1996). Intervals of
assignment in these 6 families were within the 6-Mb telomeric region of
the X chromosome and they could represent allelic disorders.
MOLECULAR GENETICS
D'Adamo et al. (1997,1998) demonstrated unique mutations in the RABGDIA
gene in affected members of the MRX41 family (300104.0001) reported by
Hamel et al. (1996) and the MRX48 family (300104.0002) reported by des
Portes et al. (1997).
Bienvenu et al. (1998) carried out mutation screening of the whole
coding region of the GDI1 gene, using a combination of denaturing
gradient gel electrophoresis and direct sequencing, in 164 patients
found negative for expansions across the FRAXA GCC repeat (309550.0004).
The authors identified a novel missense mutation in exon 11 of the GDI1
gene (300104.0003) in a French family (family R) with nonspecific mental
retardation.
In affected members of a multigenerational German family with
nonsyndromic X-linked mental retardation, Strobl-Wildemann et al. (2011)
identified a truncating mutation in the GDI1 gene (300104.0004).
*FIELD* RF
1. Bienvenu, T.; des Portes, V.; Saint Martin, A.; McDonell, N.; Billuart,
P.; Carrie, A.; Vinet, M.-C.; Couvert, P.; Toniolo, D.; Ropers, H.-H.;
Moraine, C.; van Bokhoven, H.; Fryns, J.-P.; Kahn, A.; Beldjord, C.;
Chelly, J.: Non-specific X-linked semidominant mental retardation
by mutations in a Rab GDP-dissociation inhibitor. Hum. Molec. Genet. 7:
1311-1315, 1998.
2. D'Adamo, P.; Gulisano, M.; Oostra, B. A.; Chelly, J.; Toniolo,
D.: GDI is responsible for X-linked mental retardation. (Abstract) Am.
J. Hum. Genet. 61 (suppl.): A11 only, 1997.
3. D'Adamo, P.; Menegon, A.; Lo Nigro, C.; Grasso, M.; Gulisano, M.;
Tamanini, F.; Bienvenu, T.; Gedeon, A. K.; Oostra, B.; Wu, S.-K.;
Tandon, A.; Valtorta, F.; Balch, W. E.; Chelly, J.; Toniolo, D.:
Mutations in GDI1 are responsible for X-linked non-specific mental
retardation. Nature Genet. 19: 134-139, 1998. Note: Erratum: Nature
Genet. 19: 303 only, 1998.
4. Des Portes, V.; Billuart, P.; Carrie, A.; Bachner, L.; Bienvenu,
T.; Vinet, M. C.; Beldjord, C.; Ponsot, G.; Kahn, A.; Boue, J.; Chelly,
J.: A gene for dominant nonspecific X-linked mental retardation is
located in Xq28. Am. J. Hum. Genet. 60: 903-909, 1997.
5. Hamel, B. C. J.; Kremer, H.; Wesby-van Swaay, E.; van den Helm,
B.; Smits, A. P. T.; Oostra, B. A.; Ropers, H.-H.; Mariman, E. C.
M.: A gene for nonspecific X-linked mental retardation (MRX41) is
located in the distal segment of Xq28. Am. J. Med. Genet. 64: 131-133,
1996.
6. Holinski-Feder, E.; Golla, A.; Rost, I.; Seidel, H.; Rittinger,
O.; Meindl, A.: Regional localization of two MRX genes to Xq28 (MRX28)
and to Xp11.4-Xp22.12 (MRX33). Am. J. Med. Genet. 64: 125-130, 1996.
7. Nordstrom, A.-M.; Penttinen, M.; von Koskull, H.: Linkage to Xq28
in a family with nonspecific X-linked mental retardation. Hum. Genet. 90:
263-266, 1992.
8. Strobl-Wildemann, G.; Kalscheuer, V. M.; Hu, H.; Wrogemann, K.;
Ropers, H.-H.; Tzschach, A.: Novel GDI1 mutation in a large family
with nonsyndromic X-linked intellectual disability. Am. J. Med. Genet. 155A:
3067-3070, 2011.
*FIELD* CN
Cassandra L. Kniffin - updated: 12/22/2011
*FIELD* CD
Carol A. Bocchini: 8/1/2011
*FIELD* ED
carol: 12/22/2011
ckniffin: 12/22/2011
terry: 8/2/2011
carol: 8/1/2011
*RECORD*
*FIELD* NO
300849
*FIELD* TI
#300849 MENTAL RETARDATION, X-LINKED 41; MRX41
;;MENTAL RETARDATION, X-LINKED 48; MRX48
read more*FIELD* TX
A number sign (#) is used with this entry because this form of X-linked
mental retardation, referred to as MRX41 or MRX48, is caused by mutation
in the GDI1 gene (300104) on chromosome Xq28.
CLINICAL FEATURES
Hamel et al. (1996) reported a family segregating mild to moderate
mental retardation as an X-linked trait (MRX41).
Des Portes et al. (1997) reported a large 3-generation family
segregating nonspecific X-linked mental retardation (MRX48). The
pedigree suggested X-linked semidominant inheritance: moderate to severe
mental retardation was found in 7 males and milder intellectual
impairment in 2 females, without any specific clinical, radiologic, or
biologic features.
Bienvenu et al. (1998) reported a large French family (family R) in
which all affected males showed moderate to severe mental retardation.
X-linked semidominant inheritance was strongly suggested by the severe
phenotypes in males in comparison to mildly affected females or
unaffected obligate carriers. The study suggested that the prevalence of
GDI1 mutations in nonspecific mental retardation may be 0.5 to 1%.
Strobl-Wildemann et al. (2011) reported a multigenerational German
family in which 9 males had nonsyndromic X-linked mental retardation.
The proband was noted to have absence seizures at age 12, a small
pointed chin, and crowded teeth, but no other dysmorphic features were
noted and no other patients had dysmorphic features. Two of 4 female
carriers had learning disabilities, and 1 also had attention-deficit
disorder. Strobl-Wildemann et al. (2011) noted the lack of specific
features that could alert the clinician to this form of mental
retardation.
MAPPING
By 2-point linkage analysis in a family segregating nonspecific X-linked
mental retardation (MRX41), Hamel et al. (1996) demonstrated linkage of
the disorder to marker DXS3 at Xq21.33 with a lod score of 2.56 at theta
= 0.0 and marker DXS1108 at Xq28 with a lod score of 3.82 at theta =
0.0. Multipoint linkage analysis showed that the odds for a location of
the locus at Xq28 versus Xq21.33 were 100:1.
In a large 3-generation French family segregating nonspecific X-linked
mental retardation (MRX48), des Portes et al. (1997) found linkage of
the disorder to DXS1684 with a maximum lod of 3.0 at theta = 0.0. The
authors commented that the mapping overlapped with that of MRX3 (309541)
and 4 other X-linked mental retardation families: MRX16 (300055); MRX25,
reported by Nordstrom et al. (1992); MRX28, reported by Holinski-Feder
et al. (1996); and MRX41, reported by Hamel et al. (1996). Intervals of
assignment in these 6 families were within the 6-Mb telomeric region of
the X chromosome and they could represent allelic disorders.
MOLECULAR GENETICS
D'Adamo et al. (1997,1998) demonstrated unique mutations in the RABGDIA
gene in affected members of the MRX41 family (300104.0001) reported by
Hamel et al. (1996) and the MRX48 family (300104.0002) reported by des
Portes et al. (1997).
Bienvenu et al. (1998) carried out mutation screening of the whole
coding region of the GDI1 gene, using a combination of denaturing
gradient gel electrophoresis and direct sequencing, in 164 patients
found negative for expansions across the FRAXA GCC repeat (309550.0004).
The authors identified a novel missense mutation in exon 11 of the GDI1
gene (300104.0003) in a French family (family R) with nonspecific mental
retardation.
In affected members of a multigenerational German family with
nonsyndromic X-linked mental retardation, Strobl-Wildemann et al. (2011)
identified a truncating mutation in the GDI1 gene (300104.0004).
*FIELD* RF
1. Bienvenu, T.; des Portes, V.; Saint Martin, A.; McDonell, N.; Billuart,
P.; Carrie, A.; Vinet, M.-C.; Couvert, P.; Toniolo, D.; Ropers, H.-H.;
Moraine, C.; van Bokhoven, H.; Fryns, J.-P.; Kahn, A.; Beldjord, C.;
Chelly, J.: Non-specific X-linked semidominant mental retardation
by mutations in a Rab GDP-dissociation inhibitor. Hum. Molec. Genet. 7:
1311-1315, 1998.
2. D'Adamo, P.; Gulisano, M.; Oostra, B. A.; Chelly, J.; Toniolo,
D.: GDI is responsible for X-linked mental retardation. (Abstract) Am.
J. Hum. Genet. 61 (suppl.): A11 only, 1997.
3. D'Adamo, P.; Menegon, A.; Lo Nigro, C.; Grasso, M.; Gulisano, M.;
Tamanini, F.; Bienvenu, T.; Gedeon, A. K.; Oostra, B.; Wu, S.-K.;
Tandon, A.; Valtorta, F.; Balch, W. E.; Chelly, J.; Toniolo, D.:
Mutations in GDI1 are responsible for X-linked non-specific mental
retardation. Nature Genet. 19: 134-139, 1998. Note: Erratum: Nature
Genet. 19: 303 only, 1998.
4. Des Portes, V.; Billuart, P.; Carrie, A.; Bachner, L.; Bienvenu,
T.; Vinet, M. C.; Beldjord, C.; Ponsot, G.; Kahn, A.; Boue, J.; Chelly,
J.: A gene for dominant nonspecific X-linked mental retardation is
located in Xq28. Am. J. Hum. Genet. 60: 903-909, 1997.
5. Hamel, B. C. J.; Kremer, H.; Wesby-van Swaay, E.; van den Helm,
B.; Smits, A. P. T.; Oostra, B. A.; Ropers, H.-H.; Mariman, E. C.
M.: A gene for nonspecific X-linked mental retardation (MRX41) is
located in the distal segment of Xq28. Am. J. Med. Genet. 64: 131-133,
1996.
6. Holinski-Feder, E.; Golla, A.; Rost, I.; Seidel, H.; Rittinger,
O.; Meindl, A.: Regional localization of two MRX genes to Xq28 (MRX28)
and to Xp11.4-Xp22.12 (MRX33). Am. J. Med. Genet. 64: 125-130, 1996.
7. Nordstrom, A.-M.; Penttinen, M.; von Koskull, H.: Linkage to Xq28
in a family with nonspecific X-linked mental retardation. Hum. Genet. 90:
263-266, 1992.
8. Strobl-Wildemann, G.; Kalscheuer, V. M.; Hu, H.; Wrogemann, K.;
Ropers, H.-H.; Tzschach, A.: Novel GDI1 mutation in a large family
with nonsyndromic X-linked intellectual disability. Am. J. Med. Genet. 155A:
3067-3070, 2011.
*FIELD* CN
Cassandra L. Kniffin - updated: 12/22/2011
*FIELD* CD
Carol A. Bocchini: 8/1/2011
*FIELD* ED
carol: 12/22/2011
ckniffin: 12/22/2011
terry: 8/2/2011
carol: 8/1/2011