Full text data of RAB3GAP2
RAB3GAP2
(KIAA0839)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Rab3 GTPase-activating protein non-catalytic subunit (RGAP-iso; Rab3 GTPase-activating protein 150 kDa subunit; Rab3-GAP p150; Rab3-GAP150; Rab3-GAP regulatory subunit)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Rab3 GTPase-activating protein non-catalytic subunit (RGAP-iso; Rab3 GTPase-activating protein 150 kDa subunit; Rab3-GAP p150; Rab3-GAP150; Rab3-GAP regulatory subunit)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9H2M9
ID RBGPR_HUMAN Reviewed; 1393 AA.
AC Q9H2M9; A6H8V0; O75872; Q9HAB0; Q9UFJ7; Q9UQ15;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 98.
DE RecName: Full=Rab3 GTPase-activating protein non-catalytic subunit;
DE AltName: Full=RGAP-iso;
DE AltName: Full=Rab3 GTPase-activating protein 150 kDa subunit;
DE AltName: Full=Rab3-GAP p150;
DE Short=Rab3-GAP150;
DE AltName: Full=Rab3-GAP regulatory subunit;
GN Name=RAB3GAP2; Synonyms=KIAA0839;
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 [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9733780; DOI=10.1074/jbc.273.38.24781;
RA Nagano F., Sasaki T., Fukui K., Asakura T., Imazumi K., Takai Y.;
RT "Molecular cloning and characterization of the noncatalytic subunit of
RT the Rab3 subfamily-specific GTPase-activating protein.";
RL J. Biol. Chem. 273:24781-24785(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Dendritic cell;
RA Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.;
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [4]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 930-1393.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-901, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
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 [14]
RP VARIANT MARTS CYS-1052.
RX PubMed=16532399; DOI=10.1086/502681;
RA Aligianis I.A., Morgan N.V., Mione M., Johnson C.A., Rosser E.,
RA Hennekam R.C.M., Adams G., Trembath R.C., Pilz D.T., Stoodley N.,
RA Moore A.T., Wilson S., Maher E.R.;
RT "Mutation in Rab3 GTPase-activating protein (RAB3GAP) noncatalytic
RT subunit in a kindred with Martsolf syndrome.";
RL Am. J. Hum. Genet. 78:702-707(2006).
RN [15]
RP VARIANT WARBM2 167-PHE--THR-169 DEL.
RX PubMed=20967465; DOI=10.1007/s00439-010-0896-2;
RA Borck G., Wunram H., Steiert A., Volk A.E., Korber F., Roters S.,
RA Herkenrath P., Wollnik B., Morris-Rosendahl D.J., Kubisch C.;
RT "A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome.";
RL Hum. Genet. 129:45-50(2011).
CC -!- FUNCTION: Regulatory subunit of a GTPase activating protein that
CC has specificity for Rab3 subfamily (RAB3A, RAB3B, RAB3C and
CC RAB3D). Rab3 proteins are involved in regulated exocytosis of
CC neurotransmitters and hormones. Rab3 GTPase-activating complex
CC specifically converts active Rab3-GTP to the inactive form Rab3-
CC GDP. Required for normal eye and brain development. May
CC participate in neurodevelopmental processes such as proliferation,
CC migration and differentiation before synapse formation, and non-
CC synaptic vesicular release of neurotransmitters.
CC -!- SUBUNIT: The Rab3 GTPase-activating complex is a heterodimer
CC composed of RAB3GAP and RAB3-GAP150. The Rab3 GTPase-activating
CC complex interacts with DMXL2 (By similarity).
CC -!- INTERACTION:
CC O75365:PTP4A3; NbExp=1; IntAct=EBI-536107, EBI-1043866;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=In neurons, it is enriched
CC in the synaptic soluble fraction.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H2M9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H2M9-2; Sequence=VSP_013311, VSP_013312;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Martsolf syndrome (MARTS) [MIM:212720]: Characterized by
CC congenital cataracts, mental retardation, and hypogonadism.
CC Inheritance is autosomal recessive. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- DISEASE: Warburg micro syndrome 2 (WARBM2) [MIM:614225]: A rare
CC syndrome characterized by microcephaly, microphthalmia,
CC microcornia, congenital cataracts, optic atrophy, cortical
CC dysplasia, in particular corpus callosum hypoplasia, severe mental
CC retardation, spastic diplegia, and hypogonadism. Note=The disease
CC is caused by mutations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the Rab3-GAP regulatory subunit family.
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DR EMBL; AF004828; AAC35881.1; -; mRNA.
DR EMBL; AF255648; AAG44636.1; -; mRNA.
DR EMBL; AB020646; BAA74862.2; -; mRNA.
DR EMBL; AK021928; BAB13939.1; -; mRNA.
DR EMBL; AK291234; BAF83923.1; -; mRNA.
DR EMBL; AL445435; CAI15808.1; -; Genomic_DNA.
DR EMBL; AC103590; CAI15808.1; JOINED; Genomic_DNA.
DR EMBL; CH471100; EAW93304.1; -; Genomic_DNA.
DR EMBL; BC146760; AAI46761.1; -; mRNA.
DR EMBL; AL117631; CAB56022.1; -; mRNA.
DR PIR; T17332; T17332.
DR RefSeq; NP_036546.2; NM_012414.3.
DR UniGene; Hs.654849; -.
DR UniGene; Hs.708165; -.
DR ProteinModelPortal; Q9H2M9; -.
DR IntAct; Q9H2M9; 2.
DR STRING; 9606.ENSP00000351832; -.
DR PhosphoSite; Q9H2M9; -.
DR DMDM; 62511132; -.
DR PaxDb; Q9H2M9; -.
DR PRIDE; Q9H2M9; -.
DR Ensembl; ENST00000358951; ENSP00000351832; ENSG00000118873.
DR GeneID; 25782; -.
DR KEGG; hsa:25782; -.
DR UCSC; uc001hmg.2; human.
DR CTD; 25782; -.
DR GeneCards; GC01M220322; -.
DR HGNC; HGNC:17168; RAB3GAP2.
DR HPA; HPA026273; -.
DR HPA; HPA027299; -.
DR MIM; 212720; phenotype.
DR MIM; 609275; gene.
DR MIM; 614225; phenotype.
DR neXtProt; NX_Q9H2M9; -.
DR Orphanet; 1387; Cataract - intellectual deficit - hypogonadism.
DR Orphanet; 2510; Micro syndrome.
DR PharmGKB; PA142671105; -.
DR eggNOG; NOG317114; -.
DR HOGENOM; HOG000290717; -.
DR HOVERGEN; HBG067039; -.
DR InParanoid; Q9H2M9; -.
DR OMA; QSENNGA; -.
DR OrthoDB; EOG7TTQ71; -.
DR GeneWiki; RAB3GAP2; -.
DR GenomeRNAi; 25782; -.
DR NextBio; 46935; -.
DR PRO; PR:Q9H2M9; -.
DR ArrayExpress; Q9H2M9; -.
DR Bgee; Q9H2M9; -.
DR CleanEx; HS_RAB3GAP2; -.
DR Genevestigator; Q9H2M9; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005096; F:GTPase activator activity; TAS:ProtInc.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; TAS:ProtInc.
DR InterPro; IPR026059; Rab3-gap_reg.
DR PANTHER; PTHR12472; PTHR12472; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cataract; Complete proteome; Cytoplasm;
KW Disease mutation; GTPase activation; Mental retardation;
KW Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 1393 Rab3 GTPase-activating protein non-
FT catalytic subunit.
FT /FTId=PRO_0000191662.
FT MOD_RES 450 450 Phosphoserine.
FT MOD_RES 901 901 Phosphothreonine.
FT VAR_SEQ 205 206 NE -> VV (in isoform 2).
FT /FTId=VSP_013311.
FT VAR_SEQ 207 1393 Missing (in isoform 2).
FT /FTId=VSP_013312.
FT VARIANT 167 169 Missing (in WARBM2).
FT /FTId=VAR_066675.
FT VARIANT 863 863 T -> A (in dbSNP:rs12045447).
FT /FTId=VAR_021588.
FT VARIANT 1052 1052 G -> C (in MARTS; may cause exon
FT skipping).
FT /FTId=VAR_029881.
FT VARIANT 1092 1092 S -> T (in dbSNP:rs2289189).
FT /FTId=VAR_021589.
FT CONFLICT 289 289 G -> R (in Ref. 1; AAC35881).
SQ SEQUENCE 1393 AA; 155985 MW; 4138F60B5199211E CRC64;
MACSIVQFCY FQDLQAARDF LFPHLREEIL SGALRRDPSK STDWEDDGWG AWEENEPQEP
EEEGNTCKTQ KTSWLQDCVL SLSPTNDLMV IAREQKAVFL VPKWKYSDKG KEEMQFAVGW
SGSLNVEEGE CVTSALCIPL ASQKRSSTGR PDWTCIVVGF TSGYVRFYTE NGVLLLAQLL
NEDPVLQLKC RTYEIPRHPG VTEQNEELSI LYPAAIVTID GFSLFQSLRA CRNQVAKAAA
SGNENIQPPP LAYKKWGLQD IDTIIDHASV GIMTLSPFDQ MKTASNIGGF NAAIKNSPPA
MSQYITVGSN PFTGFFYALE GSTQPLLSHV ALAVASKLTS ALFNAASGWL GWKSKHEEEA
VQKQKPKVEP ATPLAVRFGL PDSRRHGESI CLSPCNTLAA VTDDFGRVIL LDVARGIAIR
MWKGYRDAQI GWIQTVEDLH ERVPEKADFS PFGNSQGPSR VAQFLVIYAP RRGILEVWST
QQGPRVGAFN VGKHCRLLYP GYKIMGLNNV TSQSWQPQTY QICLVDPVSG SVKTVNVPFH
LALSDKKSER AKDMHLVKKL AALLKTKSPN LDLVETEIKE LILDIKYPAT KKQALESILA
SERLPFSCLR NITQTLMDTL KSQELESVDE GLLQFCANKL KLLQLYESVS QLNSLDFHLD
TPFSDNDLAL LLRLDEKELL KLQALLEKYK QENTRTNVRF SDDKDGVLPV KTFLEYLEYE
KDVLNIKKIS EEEYVALGSF FFWKCLHGES STEDMCHTLE SAGLSPQLLL SLLLSVWLSK
EKDILDKPQS ICCLHTMLSL LSKMKVAIDE TWDSQSVSPW WQQMRTACIQ SENNGAALLS
AHVGHSVAAQ ISNNMTEKKF SQTVLGADSE ALTDSWEALS LDTEYWKLLL KQLEDCLILQ
TLLHSKGNTQ TSKVSSLQAE PLPRLSVKKL LEGGKGGIAD SVAKWIFKQD FSPEVLKLAN
EERDAENPDE PKEGVNRSFL EVSEMEMDLG AIPDLLHLAY EQFPCSLELD VLHAHCCWEY
VVQWNKDPEE ARFFVRSIEH LKQIFNAHVQ NGIALMMWNT FLVKRFSAAT YLMDKVGKSP
KDRLCRRDVG MSDTAMTSFL GSCLDLLQIL MEADVSRDEI QVPVLDTEDA WLSVEGPISI
VELALEQKHI HYPLVEHHSI LCSILYAVMR FSLKTVKPLS LFDSKGKNAF FKDLTSIQLL
PSGEMDPNFI SVRQQFLLKV VSAAVQAQHS ATKVKDPTEE ATPTPFGKDQ DWPALAVDLA
HHLQVSEDVV RRHYVGELYN YGVDHLGEEA ILQVHDKEVL ASQLLVLTGQ RLAHALLHTQ
TKEGMELLAR LPPTLCTWLK AMDPQDLQNT EVPIATTAKL VNKVIELLPE KHGQYGLALH
LIEAVEAISL PSL
//
ID RBGPR_HUMAN Reviewed; 1393 AA.
AC Q9H2M9; A6H8V0; O75872; Q9HAB0; Q9UFJ7; Q9UQ15;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 98.
DE RecName: Full=Rab3 GTPase-activating protein non-catalytic subunit;
DE AltName: Full=RGAP-iso;
DE AltName: Full=Rab3 GTPase-activating protein 150 kDa subunit;
DE AltName: Full=Rab3-GAP p150;
DE Short=Rab3-GAP150;
DE AltName: Full=Rab3-GAP regulatory subunit;
GN Name=RAB3GAP2; Synonyms=KIAA0839;
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 [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9733780; DOI=10.1074/jbc.273.38.24781;
RA Nagano F., Sasaki T., Fukui K., Asakura T., Imazumi K., Takai Y.;
RT "Molecular cloning and characterization of the noncatalytic subunit of
RT the Rab3 subfamily-specific GTPase-activating protein.";
RL J. Biol. Chem. 273:24781-24785(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Dendritic cell;
RA Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.;
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [4]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 930-1393.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-901, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
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 [14]
RP VARIANT MARTS CYS-1052.
RX PubMed=16532399; DOI=10.1086/502681;
RA Aligianis I.A., Morgan N.V., Mione M., Johnson C.A., Rosser E.,
RA Hennekam R.C.M., Adams G., Trembath R.C., Pilz D.T., Stoodley N.,
RA Moore A.T., Wilson S., Maher E.R.;
RT "Mutation in Rab3 GTPase-activating protein (RAB3GAP) noncatalytic
RT subunit in a kindred with Martsolf syndrome.";
RL Am. J. Hum. Genet. 78:702-707(2006).
RN [15]
RP VARIANT WARBM2 167-PHE--THR-169 DEL.
RX PubMed=20967465; DOI=10.1007/s00439-010-0896-2;
RA Borck G., Wunram H., Steiert A., Volk A.E., Korber F., Roters S.,
RA Herkenrath P., Wollnik B., Morris-Rosendahl D.J., Kubisch C.;
RT "A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome.";
RL Hum. Genet. 129:45-50(2011).
CC -!- FUNCTION: Regulatory subunit of a GTPase activating protein that
CC has specificity for Rab3 subfamily (RAB3A, RAB3B, RAB3C and
CC RAB3D). Rab3 proteins are involved in regulated exocytosis of
CC neurotransmitters and hormones. Rab3 GTPase-activating complex
CC specifically converts active Rab3-GTP to the inactive form Rab3-
CC GDP. Required for normal eye and brain development. May
CC participate in neurodevelopmental processes such as proliferation,
CC migration and differentiation before synapse formation, and non-
CC synaptic vesicular release of neurotransmitters.
CC -!- SUBUNIT: The Rab3 GTPase-activating complex is a heterodimer
CC composed of RAB3GAP and RAB3-GAP150. The Rab3 GTPase-activating
CC complex interacts with DMXL2 (By similarity).
CC -!- INTERACTION:
CC O75365:PTP4A3; NbExp=1; IntAct=EBI-536107, EBI-1043866;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=In neurons, it is enriched
CC in the synaptic soluble fraction.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H2M9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H2M9-2; Sequence=VSP_013311, VSP_013312;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Martsolf syndrome (MARTS) [MIM:212720]: Characterized by
CC congenital cataracts, mental retardation, and hypogonadism.
CC Inheritance is autosomal recessive. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- DISEASE: Warburg micro syndrome 2 (WARBM2) [MIM:614225]: A rare
CC syndrome characterized by microcephaly, microphthalmia,
CC microcornia, congenital cataracts, optic atrophy, cortical
CC dysplasia, in particular corpus callosum hypoplasia, severe mental
CC retardation, spastic diplegia, and hypogonadism. Note=The disease
CC is caused by mutations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the Rab3-GAP regulatory subunit family.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF004828; AAC35881.1; -; mRNA.
DR EMBL; AF255648; AAG44636.1; -; mRNA.
DR EMBL; AB020646; BAA74862.2; -; mRNA.
DR EMBL; AK021928; BAB13939.1; -; mRNA.
DR EMBL; AK291234; BAF83923.1; -; mRNA.
DR EMBL; AL445435; CAI15808.1; -; Genomic_DNA.
DR EMBL; AC103590; CAI15808.1; JOINED; Genomic_DNA.
DR EMBL; CH471100; EAW93304.1; -; Genomic_DNA.
DR EMBL; BC146760; AAI46761.1; -; mRNA.
DR EMBL; AL117631; CAB56022.1; -; mRNA.
DR PIR; T17332; T17332.
DR RefSeq; NP_036546.2; NM_012414.3.
DR UniGene; Hs.654849; -.
DR UniGene; Hs.708165; -.
DR ProteinModelPortal; Q9H2M9; -.
DR IntAct; Q9H2M9; 2.
DR STRING; 9606.ENSP00000351832; -.
DR PhosphoSite; Q9H2M9; -.
DR DMDM; 62511132; -.
DR PaxDb; Q9H2M9; -.
DR PRIDE; Q9H2M9; -.
DR Ensembl; ENST00000358951; ENSP00000351832; ENSG00000118873.
DR GeneID; 25782; -.
DR KEGG; hsa:25782; -.
DR UCSC; uc001hmg.2; human.
DR CTD; 25782; -.
DR GeneCards; GC01M220322; -.
DR HGNC; HGNC:17168; RAB3GAP2.
DR HPA; HPA026273; -.
DR HPA; HPA027299; -.
DR MIM; 212720; phenotype.
DR MIM; 609275; gene.
DR MIM; 614225; phenotype.
DR neXtProt; NX_Q9H2M9; -.
DR Orphanet; 1387; Cataract - intellectual deficit - hypogonadism.
DR Orphanet; 2510; Micro syndrome.
DR PharmGKB; PA142671105; -.
DR eggNOG; NOG317114; -.
DR HOGENOM; HOG000290717; -.
DR HOVERGEN; HBG067039; -.
DR InParanoid; Q9H2M9; -.
DR OMA; QSENNGA; -.
DR OrthoDB; EOG7TTQ71; -.
DR GeneWiki; RAB3GAP2; -.
DR GenomeRNAi; 25782; -.
DR NextBio; 46935; -.
DR PRO; PR:Q9H2M9; -.
DR ArrayExpress; Q9H2M9; -.
DR Bgee; Q9H2M9; -.
DR CleanEx; HS_RAB3GAP2; -.
DR Genevestigator; Q9H2M9; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005096; F:GTPase activator activity; TAS:ProtInc.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; TAS:ProtInc.
DR InterPro; IPR026059; Rab3-gap_reg.
DR PANTHER; PTHR12472; PTHR12472; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cataract; Complete proteome; Cytoplasm;
KW Disease mutation; GTPase activation; Mental retardation;
KW Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 1393 Rab3 GTPase-activating protein non-
FT catalytic subunit.
FT /FTId=PRO_0000191662.
FT MOD_RES 450 450 Phosphoserine.
FT MOD_RES 901 901 Phosphothreonine.
FT VAR_SEQ 205 206 NE -> VV (in isoform 2).
FT /FTId=VSP_013311.
FT VAR_SEQ 207 1393 Missing (in isoform 2).
FT /FTId=VSP_013312.
FT VARIANT 167 169 Missing (in WARBM2).
FT /FTId=VAR_066675.
FT VARIANT 863 863 T -> A (in dbSNP:rs12045447).
FT /FTId=VAR_021588.
FT VARIANT 1052 1052 G -> C (in MARTS; may cause exon
FT skipping).
FT /FTId=VAR_029881.
FT VARIANT 1092 1092 S -> T (in dbSNP:rs2289189).
FT /FTId=VAR_021589.
FT CONFLICT 289 289 G -> R (in Ref. 1; AAC35881).
SQ SEQUENCE 1393 AA; 155985 MW; 4138F60B5199211E CRC64;
MACSIVQFCY FQDLQAARDF LFPHLREEIL SGALRRDPSK STDWEDDGWG AWEENEPQEP
EEEGNTCKTQ KTSWLQDCVL SLSPTNDLMV IAREQKAVFL VPKWKYSDKG KEEMQFAVGW
SGSLNVEEGE CVTSALCIPL ASQKRSSTGR PDWTCIVVGF TSGYVRFYTE NGVLLLAQLL
NEDPVLQLKC RTYEIPRHPG VTEQNEELSI LYPAAIVTID GFSLFQSLRA CRNQVAKAAA
SGNENIQPPP LAYKKWGLQD IDTIIDHASV GIMTLSPFDQ MKTASNIGGF NAAIKNSPPA
MSQYITVGSN PFTGFFYALE GSTQPLLSHV ALAVASKLTS ALFNAASGWL GWKSKHEEEA
VQKQKPKVEP ATPLAVRFGL PDSRRHGESI CLSPCNTLAA VTDDFGRVIL LDVARGIAIR
MWKGYRDAQI GWIQTVEDLH ERVPEKADFS PFGNSQGPSR VAQFLVIYAP RRGILEVWST
QQGPRVGAFN VGKHCRLLYP GYKIMGLNNV TSQSWQPQTY QICLVDPVSG SVKTVNVPFH
LALSDKKSER AKDMHLVKKL AALLKTKSPN LDLVETEIKE LILDIKYPAT KKQALESILA
SERLPFSCLR NITQTLMDTL KSQELESVDE GLLQFCANKL KLLQLYESVS QLNSLDFHLD
TPFSDNDLAL LLRLDEKELL KLQALLEKYK QENTRTNVRF SDDKDGVLPV KTFLEYLEYE
KDVLNIKKIS EEEYVALGSF FFWKCLHGES STEDMCHTLE SAGLSPQLLL SLLLSVWLSK
EKDILDKPQS ICCLHTMLSL LSKMKVAIDE TWDSQSVSPW WQQMRTACIQ SENNGAALLS
AHVGHSVAAQ ISNNMTEKKF SQTVLGADSE ALTDSWEALS LDTEYWKLLL KQLEDCLILQ
TLLHSKGNTQ TSKVSSLQAE PLPRLSVKKL LEGGKGGIAD SVAKWIFKQD FSPEVLKLAN
EERDAENPDE PKEGVNRSFL EVSEMEMDLG AIPDLLHLAY EQFPCSLELD VLHAHCCWEY
VVQWNKDPEE ARFFVRSIEH LKQIFNAHVQ NGIALMMWNT FLVKRFSAAT YLMDKVGKSP
KDRLCRRDVG MSDTAMTSFL GSCLDLLQIL MEADVSRDEI QVPVLDTEDA WLSVEGPISI
VELALEQKHI HYPLVEHHSI LCSILYAVMR FSLKTVKPLS LFDSKGKNAF FKDLTSIQLL
PSGEMDPNFI SVRQQFLLKV VSAAVQAQHS ATKVKDPTEE ATPTPFGKDQ DWPALAVDLA
HHLQVSEDVV RRHYVGELYN YGVDHLGEEA ILQVHDKEVL ASQLLVLTGQ RLAHALLHTQ
TKEGMELLAR LPPTLCTWLK AMDPQDLQNT EVPIATTAKL VNKVIELLPE KHGQYGLALH
LIEAVEAISL PSL
//
MIM
212720
*RECORD*
*FIELD* NO
212720
*FIELD* TI
#212720 MARTSOLF SYNDROME
;;CATARACT-MENTAL RETARDATION-HYPOGONADISM
*FIELD* TX
A number sign (#) is used with this entry because of evidence that some
read morecases of the Martsolf syndrome are caused by mutation in the gene
encoding the noncatalytic subunit of RAB3 GTPase-activating protein
(RAB3GAP2; 609275).
CLINICAL FEATURES
Martsolf et al. (1978) described a family in which 2 brothers had severe
mental retardation, cataracts, short stature, primary hypogonadism, and
minor digital and cephalic abnormalities. The parents were first cousins
of Polish-Jewish descent and had 1 normal daughter. There are several
mental retardation syndromes associated with cataracts, with or without
short stature. These were reviewed by Cuendet et al. (1976). The
association of mental retardation, cataracts, and primary hypogonadism
is more rare. Sanchez et al. (1985) described this syndrome in 2
brothers of Sephardic Jewish ancestry. Strisciuglio et al. (1988)
reported a non-Jewish case. Hennekam et al. (1988) described an affected
brother and sister of Dutch or Belgian ancestry. Harbord et al. (1989)
described a syndrome of microcephaly, mental retardation, cataracts, and
hypogonadism in a brother and sister with consanguineous parents of
Pakistani origin. One sib had cardiomyopathy while the other had cardiac
failure. Cardiac features had not previously been described in Martsolf
syndrome.
Seemanova and Lesny (1996) described a 6-year-old boy who had
microcephaly, microphthalmia, microcornea, congenital cataract, severe
mental deficiency, progressive spastic diplegia, hypogenitalism, and
growth retardation. Dysmorphic features included brachycephaly,
upslanting palpebral fissures, epicanthal folds, highly arched palate,
small mouth, and retrognathia. At 6 years of age, the proband was unable
to sit, walk, or speak. He had a similarly affected maternal uncle, and
2 maternal male cousins may also have been affected. Chromosomal and
metabolic findings in the proband were normal. Seemanova and Lesny
(1996) noted that the features in these patients resembled those of
several autosomal recessive disorders, including Martsolf syndrome, but
considered the phenotype distinct because of probable X-linked
inheritance.
Aligianis et al. (2006) described a consanguineous Pakistani family with
3 affected sibs. The first child had cataracts, microphthalmia,
micropenis, and cryptorchidism at birth. Spastic diplegia was noted at
the age of 3.5 years. At age 11 years, he had mild learning
difficulties, was microcephalic, and walked with a walker. The sister of
the proband likewise had dense bilateral cataracts, microphthalmia, and
microcephaly at birth. Hypotonia was noted in infancy, and she later
developed spastic diplegia. She had global developmental delay. At age 5
years, she had moderate learning difficulties and required special
schooling, but she was bilingual in English and Punjabi. The third sib
had congenitally corrected transposition of the great vessels with
micropenis, bilateral cryptorchidism, congenital cataracts, and
microphthalmia. Cardiac arrest of unknown cause occurred immediately
after cataract surgery at the age of 2 months and, following
resuscitation, he was found to have severe hypoxic ischemic
encephalopathy with convulsions.
Ehara et al. (2007) reported a Japanese brother and sister with clinical
features consistent with Martsolf syndrome. They were 31 and 24 years of
age, respectively, at the time of the report. As children, both showed
delayed motor development, short stature, cataracts, thoracic scoliosis,
and severe mental retardation. Both also developed skeletal
abnormalities of the femoral neck, including metaphyseal broadening and
fragmentation consistent with Legg-Calve-Perthes disease (150600). The
sister was found to have Klipper-Feil malformation (118100). Laboratory
evaluations showed growth hormone deficiency and lack of response to
GnRH stimulation suggesting hypothalamic-pituitary insufficiency. Brain
MRI showed enlarged Sylvian fissures, mildly dilated ventricles, and
mild cerebral atrophy. Other features included brachycephaly, short
philtrum, low posterior hairline, scoliosis, talipes valgus, flat feet,
and lax finger joints.
Bora et al. (2007) described a 7-year-old Turkish boy, born of
first-cousin parents and whose great-grandparents were also first
cousins, who had severe psychomotor retardation, microcephaly,
microphthalmia with a myotic pupil, bilateral congenital cataracts (for
which he had surgery in infancy), maxillary retrusion, dysplastic
low-set ears, long philtrum, micropenis, cryptorchidism, and pes planus
and equinovarus. Neurologic examination revealed hypotonia, 1- to 2-beat
clonus, and diminished deep tendon reflexes; the boy had difficulties in
walking and speaking, and his overall developmental age was 20 months.
Laboratory studies were normal including cholesterol; cranial MRI showed
high-intensity signals in the deep periventricular white matter.
MOLECULAR GENETICS
In a consanguineous Pakistani family with microphthalmia, congenital
cataracts, hypogonadism, and mild mental retardation, Aligianis et al.
(2006) identified a homozygous missense mutation in the noncatalytic
subunit of RAB3GAP (RAB3GAP2) that resulted in abnormal splicing
(609725.0001). Mutations in the catalytic subunit of RAB3GAP1 (602536)
cause the Warburg micro syndrome (600118), a severe neurodevelopmental
condition with clinical features overlapping those of Martsolf syndrome.
RAB3GAP is a heterodimeric protein that consists of a catalytic subunit
and a noncatalytic subunit encoded by RAB3GAP1 and RAB3GAP2,
respectively. In mRNA expression studies of the orthologs of these 2
genes in zebrafish embryos, Aligianis et al. (2006) demonstrated that,
whereas developmental expression of Rab3gap1 was generalized similar to
that reported in mice, Rab3gap2 expression was restricted to the central
nervous system. These findings were consistent with RAB3GAP2 having a
key role in neurodevelopment.
HETEROGENEITY
In the sibs with Martsolf syndrome reported by Hennekam et al. (1988),
Aligianis et al. (2006) found no mutation in the RAB3GAP2 gene,
indicating genetic heterogeneity.
*FIELD* RF
1. Aligianis, I. A.; Morgan, N. V.; Mione, M.; Johnson, C. A.; Rosser,
E.; Hennekam, R. C.; Adams, G.; Trembath, R. C.; Pilz, D. T.; Stoodley,
N.; Moore, A. T.; Wilson, S.; Maher, E. R.: Mutation in Rab3 GTPase-activating
protein (RAB3GAP) noncatalytic subunit in a kindred with Martsolf
syndrome. Am. J. Hum. Genet. 78: 702-707, 2006.
2. Bora, E.; Cankaya, T.; Alpman, A.; Karaca, E.; Cogulu, O.; Tekgul,
H.; Ozkinay, F.: A new case of Martsolf syndrome. Genet. Counsel. 18:
71-75, 2007.
3. Cuendet, J. F.; Netter, C.; Catti, A.; Verellen, C.: Association
de cataracte congenitale et d'oligophrenie. Bull. Mem. Soc. Franc.
Ophtal. 87: 164-168, 1976.
4. Ehara, H.; Utsunomiya, Y.; Ieshima, A.; Maegaki, Y.; Nishimura,
G.; Takeshita, K.; Ohno, K.: Martsolf syndrome in Japanese siblings. Am.
J. Med. Genet. 143A: 973-978, 2007.
5. Harbord, M. G.; Baraitser, M.; Wilson, J.: Microcephaly, mental
retardation, cataracts, and hypogonadism in sibs: Martsolf's syndrome. J.
Med. Genet. 26: 397-406, 1989.
6. Hennekam, R. C. M.; vandeMeeberg, A. G.; vanDoorne, J. M.; Dijkstra,
P. F.; Bijlsma, J. B.: Martsolf syndrome in a brother and sister:
clinical features and pattern of inheritance. Europ. J. Pediat. 147:
539-543, 1988.
7. Martsolf, J. T.; Hunter, A. G. W.; Haworth, J. C.: Severe mental
retardation, cataracts, short stature and primary hypogonadism in
two brothers. Am. J. Med. Genet. 1: 291-299, 1978.
8. Sanchez, J. M.; Barreiro, C.; Freilij, H.: Two brothers with Martsolf's
syndrome. J. Med. Genet. 22: 308-310, 1985.
9. Seemanova, E.; Lesny, I.: X-linked microcephaly, microphthalmia,
microcornea, congenital cataract, hypogenitalism, mental deficiency,
growth retardation, spasticity: possible new syndrome. Am. J. Med.
Genet. 66: 179-183, 1996.
10. Strisciuglio, P.; Costabile, M.; Esposito, M.; Di Maio, S.: Martsolf's
syndrome in a non-Jewish boy. J. Med. Genet. 25: 267-269, 1988.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature;
Height less than 5th percentile;
[Weight];
Weight less than 5th percentile
HEAD AND NECK:
[Head];
Brachycephaly;
Microcephaly;
[Face];
Mild maxillary hypoplasia;
Micrognathia;
Short philtrum;
[Ears];
Prominent antitragus;
Posteriorly rotated ears;
[Eyes];
Cataracts;
Epicanthal fold;
Downward-slanting palpebral fissures;
[Nose];
Low nasal bridge;
Broad nasal tip;
[Mouth];
Pouty lower lip;
High palate;
[Teeth];
Malaligned teeth
CARDIOVASCULAR:
[Heart];
Cardiomyopathy;
Cardiac failure
RESPIRATORY:
Recurrent respiratory infections;
[Airways];
Tracheomalacia
CHEST:
[Ribs, sternum, clavicles, and scapulae];
Pectus carinatum;
Pectus excavatum;
[Breasts];
Prominent nipples
ABDOMEN:
[Gastrointestinal];
Feeding problems (infancy)
GENITOURINARY:
[External genitalia, male];
Small penis;
[Internal genitalia, male];
Cryptorchidism
SKELETAL:
[Spine];
Lumbar hyperlordosis;
[Limbs];
Thin limbs;
Slender radii;
Slender ulnae;
[Hands];
Short palms;
Broad fingertips;
Finger joint laxity;
Short metacarpals;
Short phalanges;
[Feet];
Metatarsus varus;
Short toes;
Clubfoot;
Talipes valgus
SKIN, NAILS, HAIR:
[Nails];
Abnormal toenails
NEUROLOGIC:
[Central nervous system];
Mental retardation, severe
ENDOCRINE FEATURES:
Hypogonadotropic hypogonadism
MOLECULAR BASIS:
Caused by mutation in the RAB3 GTPase-activating protein, noncatalytic
subunit gene (RAB3GAP2, 609275.0001)
*FIELD* CN
Kelly A. Przylepa - revised: 12/24/2007
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
terry: 10/12/2010
joanna: 1/15/2008
joanna: 12/24/2007
alopez: 3/17/2006
*FIELD* CN
Marla J. F. O'Neill - updated: 10/31/2011
Marla J. F. O'Neill - updated: 7/18/2007
Cassandra L. Kniffin - updated: 7/17/2007
Victor A. McKusick - updated: 3/15/2006
*FIELD* CD
Victor A. McKusick: 6/3/1986
*FIELD* ED
carol: 10/31/2011
terry: 10/31/2011
wwang: 7/18/2007
ckniffin: 7/17/2007
carol: 5/16/2007
alopez: 3/17/2006
terry: 3/15/2006
mimadm: 2/19/1994
carol: 3/31/1992
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
root: 7/3/1989
*RECORD*
*FIELD* NO
212720
*FIELD* TI
#212720 MARTSOLF SYNDROME
;;CATARACT-MENTAL RETARDATION-HYPOGONADISM
*FIELD* TX
A number sign (#) is used with this entry because of evidence that some
read morecases of the Martsolf syndrome are caused by mutation in the gene
encoding the noncatalytic subunit of RAB3 GTPase-activating protein
(RAB3GAP2; 609275).
CLINICAL FEATURES
Martsolf et al. (1978) described a family in which 2 brothers had severe
mental retardation, cataracts, short stature, primary hypogonadism, and
minor digital and cephalic abnormalities. The parents were first cousins
of Polish-Jewish descent and had 1 normal daughter. There are several
mental retardation syndromes associated with cataracts, with or without
short stature. These were reviewed by Cuendet et al. (1976). The
association of mental retardation, cataracts, and primary hypogonadism
is more rare. Sanchez et al. (1985) described this syndrome in 2
brothers of Sephardic Jewish ancestry. Strisciuglio et al. (1988)
reported a non-Jewish case. Hennekam et al. (1988) described an affected
brother and sister of Dutch or Belgian ancestry. Harbord et al. (1989)
described a syndrome of microcephaly, mental retardation, cataracts, and
hypogonadism in a brother and sister with consanguineous parents of
Pakistani origin. One sib had cardiomyopathy while the other had cardiac
failure. Cardiac features had not previously been described in Martsolf
syndrome.
Seemanova and Lesny (1996) described a 6-year-old boy who had
microcephaly, microphthalmia, microcornea, congenital cataract, severe
mental deficiency, progressive spastic diplegia, hypogenitalism, and
growth retardation. Dysmorphic features included brachycephaly,
upslanting palpebral fissures, epicanthal folds, highly arched palate,
small mouth, and retrognathia. At 6 years of age, the proband was unable
to sit, walk, or speak. He had a similarly affected maternal uncle, and
2 maternal male cousins may also have been affected. Chromosomal and
metabolic findings in the proband were normal. Seemanova and Lesny
(1996) noted that the features in these patients resembled those of
several autosomal recessive disorders, including Martsolf syndrome, but
considered the phenotype distinct because of probable X-linked
inheritance.
Aligianis et al. (2006) described a consanguineous Pakistani family with
3 affected sibs. The first child had cataracts, microphthalmia,
micropenis, and cryptorchidism at birth. Spastic diplegia was noted at
the age of 3.5 years. At age 11 years, he had mild learning
difficulties, was microcephalic, and walked with a walker. The sister of
the proband likewise had dense bilateral cataracts, microphthalmia, and
microcephaly at birth. Hypotonia was noted in infancy, and she later
developed spastic diplegia. She had global developmental delay. At age 5
years, she had moderate learning difficulties and required special
schooling, but she was bilingual in English and Punjabi. The third sib
had congenitally corrected transposition of the great vessels with
micropenis, bilateral cryptorchidism, congenital cataracts, and
microphthalmia. Cardiac arrest of unknown cause occurred immediately
after cataract surgery at the age of 2 months and, following
resuscitation, he was found to have severe hypoxic ischemic
encephalopathy with convulsions.
Ehara et al. (2007) reported a Japanese brother and sister with clinical
features consistent with Martsolf syndrome. They were 31 and 24 years of
age, respectively, at the time of the report. As children, both showed
delayed motor development, short stature, cataracts, thoracic scoliosis,
and severe mental retardation. Both also developed skeletal
abnormalities of the femoral neck, including metaphyseal broadening and
fragmentation consistent with Legg-Calve-Perthes disease (150600). The
sister was found to have Klipper-Feil malformation (118100). Laboratory
evaluations showed growth hormone deficiency and lack of response to
GnRH stimulation suggesting hypothalamic-pituitary insufficiency. Brain
MRI showed enlarged Sylvian fissures, mildly dilated ventricles, and
mild cerebral atrophy. Other features included brachycephaly, short
philtrum, low posterior hairline, scoliosis, talipes valgus, flat feet,
and lax finger joints.
Bora et al. (2007) described a 7-year-old Turkish boy, born of
first-cousin parents and whose great-grandparents were also first
cousins, who had severe psychomotor retardation, microcephaly,
microphthalmia with a myotic pupil, bilateral congenital cataracts (for
which he had surgery in infancy), maxillary retrusion, dysplastic
low-set ears, long philtrum, micropenis, cryptorchidism, and pes planus
and equinovarus. Neurologic examination revealed hypotonia, 1- to 2-beat
clonus, and diminished deep tendon reflexes; the boy had difficulties in
walking and speaking, and his overall developmental age was 20 months.
Laboratory studies were normal including cholesterol; cranial MRI showed
high-intensity signals in the deep periventricular white matter.
MOLECULAR GENETICS
In a consanguineous Pakistani family with microphthalmia, congenital
cataracts, hypogonadism, and mild mental retardation, Aligianis et al.
(2006) identified a homozygous missense mutation in the noncatalytic
subunit of RAB3GAP (RAB3GAP2) that resulted in abnormal splicing
(609725.0001). Mutations in the catalytic subunit of RAB3GAP1 (602536)
cause the Warburg micro syndrome (600118), a severe neurodevelopmental
condition with clinical features overlapping those of Martsolf syndrome.
RAB3GAP is a heterodimeric protein that consists of a catalytic subunit
and a noncatalytic subunit encoded by RAB3GAP1 and RAB3GAP2,
respectively. In mRNA expression studies of the orthologs of these 2
genes in zebrafish embryos, Aligianis et al. (2006) demonstrated that,
whereas developmental expression of Rab3gap1 was generalized similar to
that reported in mice, Rab3gap2 expression was restricted to the central
nervous system. These findings were consistent with RAB3GAP2 having a
key role in neurodevelopment.
HETEROGENEITY
In the sibs with Martsolf syndrome reported by Hennekam et al. (1988),
Aligianis et al. (2006) found no mutation in the RAB3GAP2 gene,
indicating genetic heterogeneity.
*FIELD* RF
1. Aligianis, I. A.; Morgan, N. V.; Mione, M.; Johnson, C. A.; Rosser,
E.; Hennekam, R. C.; Adams, G.; Trembath, R. C.; Pilz, D. T.; Stoodley,
N.; Moore, A. T.; Wilson, S.; Maher, E. R.: Mutation in Rab3 GTPase-activating
protein (RAB3GAP) noncatalytic subunit in a kindred with Martsolf
syndrome. Am. J. Hum. Genet. 78: 702-707, 2006.
2. Bora, E.; Cankaya, T.; Alpman, A.; Karaca, E.; Cogulu, O.; Tekgul,
H.; Ozkinay, F.: A new case of Martsolf syndrome. Genet. Counsel. 18:
71-75, 2007.
3. Cuendet, J. F.; Netter, C.; Catti, A.; Verellen, C.: Association
de cataracte congenitale et d'oligophrenie. Bull. Mem. Soc. Franc.
Ophtal. 87: 164-168, 1976.
4. Ehara, H.; Utsunomiya, Y.; Ieshima, A.; Maegaki, Y.; Nishimura,
G.; Takeshita, K.; Ohno, K.: Martsolf syndrome in Japanese siblings. Am.
J. Med. Genet. 143A: 973-978, 2007.
5. Harbord, M. G.; Baraitser, M.; Wilson, J.: Microcephaly, mental
retardation, cataracts, and hypogonadism in sibs: Martsolf's syndrome. J.
Med. Genet. 26: 397-406, 1989.
6. Hennekam, R. C. M.; vandeMeeberg, A. G.; vanDoorne, J. M.; Dijkstra,
P. F.; Bijlsma, J. B.: Martsolf syndrome in a brother and sister:
clinical features and pattern of inheritance. Europ. J. Pediat. 147:
539-543, 1988.
7. Martsolf, J. T.; Hunter, A. G. W.; Haworth, J. C.: Severe mental
retardation, cataracts, short stature and primary hypogonadism in
two brothers. Am. J. Med. Genet. 1: 291-299, 1978.
8. Sanchez, J. M.; Barreiro, C.; Freilij, H.: Two brothers with Martsolf's
syndrome. J. Med. Genet. 22: 308-310, 1985.
9. Seemanova, E.; Lesny, I.: X-linked microcephaly, microphthalmia,
microcornea, congenital cataract, hypogenitalism, mental deficiency,
growth retardation, spasticity: possible new syndrome. Am. J. Med.
Genet. 66: 179-183, 1996.
10. Strisciuglio, P.; Costabile, M.; Esposito, M.; Di Maio, S.: Martsolf's
syndrome in a non-Jewish boy. J. Med. Genet. 25: 267-269, 1988.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature;
Height less than 5th percentile;
[Weight];
Weight less than 5th percentile
HEAD AND NECK:
[Head];
Brachycephaly;
Microcephaly;
[Face];
Mild maxillary hypoplasia;
Micrognathia;
Short philtrum;
[Ears];
Prominent antitragus;
Posteriorly rotated ears;
[Eyes];
Cataracts;
Epicanthal fold;
Downward-slanting palpebral fissures;
[Nose];
Low nasal bridge;
Broad nasal tip;
[Mouth];
Pouty lower lip;
High palate;
[Teeth];
Malaligned teeth
CARDIOVASCULAR:
[Heart];
Cardiomyopathy;
Cardiac failure
RESPIRATORY:
Recurrent respiratory infections;
[Airways];
Tracheomalacia
CHEST:
[Ribs, sternum, clavicles, and scapulae];
Pectus carinatum;
Pectus excavatum;
[Breasts];
Prominent nipples
ABDOMEN:
[Gastrointestinal];
Feeding problems (infancy)
GENITOURINARY:
[External genitalia, male];
Small penis;
[Internal genitalia, male];
Cryptorchidism
SKELETAL:
[Spine];
Lumbar hyperlordosis;
[Limbs];
Thin limbs;
Slender radii;
Slender ulnae;
[Hands];
Short palms;
Broad fingertips;
Finger joint laxity;
Short metacarpals;
Short phalanges;
[Feet];
Metatarsus varus;
Short toes;
Clubfoot;
Talipes valgus
SKIN, NAILS, HAIR:
[Nails];
Abnormal toenails
NEUROLOGIC:
[Central nervous system];
Mental retardation, severe
ENDOCRINE FEATURES:
Hypogonadotropic hypogonadism
MOLECULAR BASIS:
Caused by mutation in the RAB3 GTPase-activating protein, noncatalytic
subunit gene (RAB3GAP2, 609275.0001)
*FIELD* CN
Kelly A. Przylepa - revised: 12/24/2007
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
terry: 10/12/2010
joanna: 1/15/2008
joanna: 12/24/2007
alopez: 3/17/2006
*FIELD* CN
Marla J. F. O'Neill - updated: 10/31/2011
Marla J. F. O'Neill - updated: 7/18/2007
Cassandra L. Kniffin - updated: 7/17/2007
Victor A. McKusick - updated: 3/15/2006
*FIELD* CD
Victor A. McKusick: 6/3/1986
*FIELD* ED
carol: 10/31/2011
terry: 10/31/2011
wwang: 7/18/2007
ckniffin: 7/17/2007
carol: 5/16/2007
alopez: 3/17/2006
terry: 3/15/2006
mimadm: 2/19/1994
carol: 3/31/1992
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
root: 7/3/1989
MIM
609275
*RECORD*
*FIELD* NO
609275
*FIELD* TI
*609275 RAB3 GTPase-ACTIVATING PROTEIN, NONCATALYTIC SUBUNIT; RAB3GAP2
;;RAB3GAP, 150-KD SUBUNIT; RAB3GAP150;;
read morep150;;
KIAA0839
*FIELD* TX
DESCRIPTION
Members of the RAB3 protein family (see RAB3A; 179490) are implicated in
Ca(2+)-dependent exocytosis. RAB3GAP, which is involved in regulation of
RAB3 activity, is a heterodimeric complex consisting a 130-kD catalytic
subunit (RAB3GAP1; 602536) and a 150-kD noncatalytic subunit (RAB3GAP2)
(Nagano et al., 1998).
CLONING
By database analysis to identify human peptide sequences similar to the
150-kD noncatalytic subunit of rat Rab3gap (p150), followed by PCR,
library screening, and 5-prime RACE of a brain cDNA library, Nagano et
al. (1998) cloned human p150. The deduced protein contains 1,393 amino
acids. Northern blot analysis detected a 7.5-kb transcript in all human
tissues examined. Western blot analysis of subcellular fractionated rat
brain detected p150 enriched in the synaptic soluble fraction.
By sequencing clones obtained from a size-fractionated brain cDNA
library, Nagase et al. (1998) cloned KIAA0839. RT-PCR ELISA detected
highest expression in brain, followed by kidney, ovary, and heart.
Intermediate expression was detected in all other tissues examined.
GENE FUNCTION
By coimmunoprecipitation of rat brain synaptic soluble fractions, Nagano
et al. (1998) found a strong direct interaction between p150 and a
130-kD protein (p130) that showed GAP activity toward Rab3 family
members. p150 did not show GAP activity, and the interaction between
p150 and p130 did not alter the activity of p130 or the subcellular
distribution of the 2 proteins.
In mRNA expression studies of the orthologs of RAB3GAP1 and RAB3GAP2 in
zebrafish embryos, Aligianis et al. (2006) demonstrated that, whereas
developmental expression of Rab3gap1 was generalized similar to that
reported in mice, Rab3gap2 expression was restricted to the central
nervous system. These findings were consistent with RAB3GAP2 having a
key role in neurodevelopment.
GENE STRUCTURE
Aligianis et al. (2006) stated that the RAB3GAP2 gene comprises 36
exons.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the
RAB3GAP150 gene to chromosome 1 (TMAP SHGC-24046).
MOLECULAR GENETICS
- Martsolf Syndrome
Aligianis et al. (2006) identified a homozygous missense mutation in the
noncatalytic subunit of RAB3GAP (609275.0001) that resulted in abnormal
splicing in a family with congenital cataracts, hypogonadism, and mild
mental retardation (Martsolf syndrome; 212720). The heterodimeric
complex RAB3GAP consists of a catalytic subunit and a noncatalytic
subunit encoded by RAB3GAP1 (602536) and RAB3GAP2, respectively.
Expression studies in zebrafish yielded results consistent with RAB3GAP2
having a key role in neurodevelopment. Aligianis et al. (2006) suggested
that this may indicate that Warburg micro syndrome (600118), which had
been shown to have mutations in RAB3GAP1, and Martsolf syndrome
represent a spectrum of disorders. However, Aligianis et al. (2006)
detected no RAB3GAP2 mutations in patients with Warburg Micro syndrome.
Together, these findings suggested that dysregulation of RAB3GAP may
result in a spectrum of phenotypes that range from Warburg micro
syndrome to Martsolf syndrome.
- Warburg Micro Syndrome 2
In a patient with Warburg Micro syndrome-2 (WARBM2; 614225), Borck et
al. (2011) identified a homozygous in-frame deletion of 9 bp in exon 6
of the RAB3GAP2 gene (609275.0002).
GENOTYPE/PHENOTYPE CORRELATIONS
Borck et al. (2011) suggested that functionally severe RAB3GAP2
mutations cause Warburg Micro syndrome-2, whereas hypomorphic RAB3GAP2
mutations can result in the milder Martsolf phenotype. They thus
proposed that a phenotypic severity gradient may exist in the
RAB3GAP-associated disease continuum (the 'Warburg-Martsolf syndrome'),
which is presumably determined by the mutant gene and the nature of the
mutation.
*FIELD* AV
.0001
MARTSOLF SYNDROME
RAB3GAP2, GLY1051CYS
In 3 sibs from a consanguineous Pakistani family with Martsolf syndrome
(212720), Aligianis et al. (2006) found a homozygous 3154G-T (gly1051 to
cys) substitution in the RAB3GAP2 gene. Both parents were heterozygous
for this substitution. In studies of lymphocyte RNA, Aligianis et al.
(2006) found that the G1051C mutation resulted in 2 transcripts. The
substitution is adjacent to the exon 28 splice donor site and resulted
in exon 28 skipping and frameshift.
.0002
WARBURG MICRO SYNDROME 2
RAB3GAP2, 9-BP DEL, NT499
In a girl from a consanguineous Turkish family with Warburg Micro
syndrome-2 (614225), Borck et al. (2011) identified a homozygous
RAB3GAP2 9-bp in-frame deletion (499_507delTTCTACACT). The mutation was
predicted to lead to the deletion of the amino acids phenylalanine,
tyrosine and threonine at positions 167-169 of the protein
(Phe167_Thr169del). The parents were heterozygous carriers of the
mutation, which was absent in 288 Turkish and 170 German control
chromosomes. RT-PCR on lymphocyte RNA from the patient confirmed the
homozygous 9-bp deletion at the mRNA level and detected no aberrant
splicing.
*FIELD* RF
1. Aligianis, I. A.; Morgan, N. V.; Mione, M.; Johnson, C. A.; Rosser,
E.; Hennekam, R. C.; Adams, G.; Trembath, R. C.; Pilz, D. T.; Stoodley,
N.; Moore, A. T.; Wilson, S.; Maher, E. R.: Mutation in Rab3 GTPase-activating
protein (RAB3GAP) noncatalytic subunit in a kindred with Martsolf
syndrome. Am. J. Hum. Genet. 78: 702-707, 2006.
2. Borck, G.; Wunram, H.; Steiert, A.; Volk, A. E.; Korber, F.; Roters,
S.; Herkenrath, P.; Wollnik, B.; Morris-Rosendahl, D. J.; Kubisch,
C.: A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. Hum.
Genet. 129: 45-50, 2011.
3. Nagano, F.; Sasaki, T.; Fukui, K.; Asakura, T.; Imazumi, K.; Takai,
Y.: Molecular cloning and characterization of the noncatalytic subunit
of the Rab3 subfamily-specific GTPase-activating protein. J. Biol.
Chem. 273: 24781-24785, 1998.
4. Nagase, T.; Ishikawa, K.; Suyama, M.; Kikuno, R.; Hirosawa, M.;
Miyajima, N.; Tanaka, A.; Kotani, H.; Nomura, N.; Oharo, O.: Prediction
of the coding sequences of unidentified human genes. XII. The complete
sequences of 100 new cDNA clones from brain which code for large proteins
in vitro. DNA Res. 5: 355-364, 1998.
*FIELD* CN
Nara Sobreira - updated: 9/14/2011
Victor A. McKusick - updated: 3/15/2006
*FIELD* CD
Patricia A. Hartz: 3/25/2005
*FIELD* ED
carol: 10/28/2011
carol: 9/14/2011
terry: 9/14/2011
alopez: 3/17/2006
terry: 3/15/2006
mgross: 3/25/2005
*RECORD*
*FIELD* NO
609275
*FIELD* TI
*609275 RAB3 GTPase-ACTIVATING PROTEIN, NONCATALYTIC SUBUNIT; RAB3GAP2
;;RAB3GAP, 150-KD SUBUNIT; RAB3GAP150;;
read morep150;;
KIAA0839
*FIELD* TX
DESCRIPTION
Members of the RAB3 protein family (see RAB3A; 179490) are implicated in
Ca(2+)-dependent exocytosis. RAB3GAP, which is involved in regulation of
RAB3 activity, is a heterodimeric complex consisting a 130-kD catalytic
subunit (RAB3GAP1; 602536) and a 150-kD noncatalytic subunit (RAB3GAP2)
(Nagano et al., 1998).
CLONING
By database analysis to identify human peptide sequences similar to the
150-kD noncatalytic subunit of rat Rab3gap (p150), followed by PCR,
library screening, and 5-prime RACE of a brain cDNA library, Nagano et
al. (1998) cloned human p150. The deduced protein contains 1,393 amino
acids. Northern blot analysis detected a 7.5-kb transcript in all human
tissues examined. Western blot analysis of subcellular fractionated rat
brain detected p150 enriched in the synaptic soluble fraction.
By sequencing clones obtained from a size-fractionated brain cDNA
library, Nagase et al. (1998) cloned KIAA0839. RT-PCR ELISA detected
highest expression in brain, followed by kidney, ovary, and heart.
Intermediate expression was detected in all other tissues examined.
GENE FUNCTION
By coimmunoprecipitation of rat brain synaptic soluble fractions, Nagano
et al. (1998) found a strong direct interaction between p150 and a
130-kD protein (p130) that showed GAP activity toward Rab3 family
members. p150 did not show GAP activity, and the interaction between
p150 and p130 did not alter the activity of p130 or the subcellular
distribution of the 2 proteins.
In mRNA expression studies of the orthologs of RAB3GAP1 and RAB3GAP2 in
zebrafish embryos, Aligianis et al. (2006) demonstrated that, whereas
developmental expression of Rab3gap1 was generalized similar to that
reported in mice, Rab3gap2 expression was restricted to the central
nervous system. These findings were consistent with RAB3GAP2 having a
key role in neurodevelopment.
GENE STRUCTURE
Aligianis et al. (2006) stated that the RAB3GAP2 gene comprises 36
exons.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the
RAB3GAP150 gene to chromosome 1 (TMAP SHGC-24046).
MOLECULAR GENETICS
- Martsolf Syndrome
Aligianis et al. (2006) identified a homozygous missense mutation in the
noncatalytic subunit of RAB3GAP (609275.0001) that resulted in abnormal
splicing in a family with congenital cataracts, hypogonadism, and mild
mental retardation (Martsolf syndrome; 212720). The heterodimeric
complex RAB3GAP consists of a catalytic subunit and a noncatalytic
subunit encoded by RAB3GAP1 (602536) and RAB3GAP2, respectively.
Expression studies in zebrafish yielded results consistent with RAB3GAP2
having a key role in neurodevelopment. Aligianis et al. (2006) suggested
that this may indicate that Warburg micro syndrome (600118), which had
been shown to have mutations in RAB3GAP1, and Martsolf syndrome
represent a spectrum of disorders. However, Aligianis et al. (2006)
detected no RAB3GAP2 mutations in patients with Warburg Micro syndrome.
Together, these findings suggested that dysregulation of RAB3GAP may
result in a spectrum of phenotypes that range from Warburg micro
syndrome to Martsolf syndrome.
- Warburg Micro Syndrome 2
In a patient with Warburg Micro syndrome-2 (WARBM2; 614225), Borck et
al. (2011) identified a homozygous in-frame deletion of 9 bp in exon 6
of the RAB3GAP2 gene (609275.0002).
GENOTYPE/PHENOTYPE CORRELATIONS
Borck et al. (2011) suggested that functionally severe RAB3GAP2
mutations cause Warburg Micro syndrome-2, whereas hypomorphic RAB3GAP2
mutations can result in the milder Martsolf phenotype. They thus
proposed that a phenotypic severity gradient may exist in the
RAB3GAP-associated disease continuum (the 'Warburg-Martsolf syndrome'),
which is presumably determined by the mutant gene and the nature of the
mutation.
*FIELD* AV
.0001
MARTSOLF SYNDROME
RAB3GAP2, GLY1051CYS
In 3 sibs from a consanguineous Pakistani family with Martsolf syndrome
(212720), Aligianis et al. (2006) found a homozygous 3154G-T (gly1051 to
cys) substitution in the RAB3GAP2 gene. Both parents were heterozygous
for this substitution. In studies of lymphocyte RNA, Aligianis et al.
(2006) found that the G1051C mutation resulted in 2 transcripts. The
substitution is adjacent to the exon 28 splice donor site and resulted
in exon 28 skipping and frameshift.
.0002
WARBURG MICRO SYNDROME 2
RAB3GAP2, 9-BP DEL, NT499
In a girl from a consanguineous Turkish family with Warburg Micro
syndrome-2 (614225), Borck et al. (2011) identified a homozygous
RAB3GAP2 9-bp in-frame deletion (499_507delTTCTACACT). The mutation was
predicted to lead to the deletion of the amino acids phenylalanine,
tyrosine and threonine at positions 167-169 of the protein
(Phe167_Thr169del). The parents were heterozygous carriers of the
mutation, which was absent in 288 Turkish and 170 German control
chromosomes. RT-PCR on lymphocyte RNA from the patient confirmed the
homozygous 9-bp deletion at the mRNA level and detected no aberrant
splicing.
*FIELD* RF
1. Aligianis, I. A.; Morgan, N. V.; Mione, M.; Johnson, C. A.; Rosser,
E.; Hennekam, R. C.; Adams, G.; Trembath, R. C.; Pilz, D. T.; Stoodley,
N.; Moore, A. T.; Wilson, S.; Maher, E. R.: Mutation in Rab3 GTPase-activating
protein (RAB3GAP) noncatalytic subunit in a kindred with Martsolf
syndrome. Am. J. Hum. Genet. 78: 702-707, 2006.
2. Borck, G.; Wunram, H.; Steiert, A.; Volk, A. E.; Korber, F.; Roters,
S.; Herkenrath, P.; Wollnik, B.; Morris-Rosendahl, D. J.; Kubisch,
C.: A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. Hum.
Genet. 129: 45-50, 2011.
3. Nagano, F.; Sasaki, T.; Fukui, K.; Asakura, T.; Imazumi, K.; Takai,
Y.: Molecular cloning and characterization of the noncatalytic subunit
of the Rab3 subfamily-specific GTPase-activating protein. J. Biol.
Chem. 273: 24781-24785, 1998.
4. Nagase, T.; Ishikawa, K.; Suyama, M.; Kikuno, R.; Hirosawa, M.;
Miyajima, N.; Tanaka, A.; Kotani, H.; Nomura, N.; Oharo, O.: Prediction
of the coding sequences of unidentified human genes. XII. The complete
sequences of 100 new cDNA clones from brain which code for large proteins
in vitro. DNA Res. 5: 355-364, 1998.
*FIELD* CN
Nara Sobreira - updated: 9/14/2011
Victor A. McKusick - updated: 3/15/2006
*FIELD* CD
Patricia A. Hartz: 3/25/2005
*FIELD* ED
carol: 10/28/2011
carol: 9/14/2011
terry: 9/14/2011
alopez: 3/17/2006
terry: 3/15/2006
mgross: 3/25/2005
MIM
614225
*RECORD*
*FIELD* NO
614225
*FIELD* TI
#614225 WARBURG MICRO SYNDROME 2; WARBM2
;;MICRO SYNDROME 2
*FIELD* TX
A number sign (#) is used with this entry because Warburg Micro
read moresyndrome-2 (WARBM2) can be caused by homozygous mutation in the RAB3GAP2
gene (609275) on chromosome 1q41.
For a general phenotypic description and a discussion of genetic
heterogeneity of Warburg Micro syndrome, see 600118.
CLINICAL FEATURES
Borck et al. (2011) reported a girl from a consanguineous Turkish family
with Warburg Micro syndrome who presented with congenital cataracts,
microphthalmia, absent visual evoked potentials, microcephaly,
polymicrogyria, hypoplasia of the corpus callosum, and severe
developmental delay.
MOLECULAR GENETICS
In a girl from a consanguineous Turkish family with Warburg Micro
syndrome, Borck et al. (2011) identified homozygosity for a small
in-frame deletion in the RAB3GAP2 gene (609275.0002). The parents were
heterozygous carriers of the mutation, which was not found in 188
Turkish and 170 German control chromosomes.
*FIELD* RF
1. Borck, G.; Wunram, H.; Steiert, A.; Volk, A. E.; Korber, F.; Roters,
S.; Herkenrath, P.; Wollnik, B.; Morris-Rosendahl, D. J.; Kubisch,
C.: A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. Hum.
Genet. 129: 45-50, 2011.
*FIELD* CD
Nara Sobreira: 9/14/2011
*FIELD* ED
carol: 01/12/2012
carol: 9/14/2011
*RECORD*
*FIELD* NO
614225
*FIELD* TI
#614225 WARBURG MICRO SYNDROME 2; WARBM2
;;MICRO SYNDROME 2
*FIELD* TX
A number sign (#) is used with this entry because Warburg Micro
read moresyndrome-2 (WARBM2) can be caused by homozygous mutation in the RAB3GAP2
gene (609275) on chromosome 1q41.
For a general phenotypic description and a discussion of genetic
heterogeneity of Warburg Micro syndrome, see 600118.
CLINICAL FEATURES
Borck et al. (2011) reported a girl from a consanguineous Turkish family
with Warburg Micro syndrome who presented with congenital cataracts,
microphthalmia, absent visual evoked potentials, microcephaly,
polymicrogyria, hypoplasia of the corpus callosum, and severe
developmental delay.
MOLECULAR GENETICS
In a girl from a consanguineous Turkish family with Warburg Micro
syndrome, Borck et al. (2011) identified homozygosity for a small
in-frame deletion in the RAB3GAP2 gene (609275.0002). The parents were
heterozygous carriers of the mutation, which was not found in 188
Turkish and 170 German control chromosomes.
*FIELD* RF
1. Borck, G.; Wunram, H.; Steiert, A.; Volk, A. E.; Korber, F.; Roters,
S.; Herkenrath, P.; Wollnik, B.; Morris-Rosendahl, D. J.; Kubisch,
C.: A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. Hum.
Genet. 129: 45-50, 2011.
*FIELD* CD
Nara Sobreira: 9/14/2011
*FIELD* ED
carol: 01/12/2012
carol: 9/14/2011