RBCC

Full text data of RAB23

RAB23 [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Ras-related protein Rab-23; Flags: Precursor

UniProt Q9ULC3
ID RAB23_HUMAN Reviewed; 237 AA.
AC Q9ULC3; B2R9I5; Q68DJ6; Q8NI06; Q9P023;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=Ras-related protein Rab-23;
DE Flags: Precursor;
GN Name=RAB23; ORFNames=HSPC137;
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].
RC TISSUE=Fetal brain;
RA Seki N., Yoshikawa T., Azuma T., Saito T., Muramatsu M.;
RT "Human mRNA for RAB23 protein.";
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hair follicle;
RA Ikeda A., Yamashita M.;
RT "Expression of RAB-23 in human hair follicle.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-207.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-207.
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction
RT sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon carcinoma;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [8]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [11]
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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=21255211; DOI=10.1111/j.1600-0854.2011.01165.x;
RA Seto S., Tsujimura K., Koide Y.;
RT "Rab GTPases regulating phagosome maturation are differentially
RT recruited to mycobacterial phagosomes.";
RL Traffic 12:407-420(2011).
RN [14]
RP FUNCTION.
RX PubMed=22452336; DOI=10.1111/j.1462-5822.2012.01792.x;
RA Nozawa T., Aikawa C., Goda A., Maruyama F., Hamada S., Nakagawa I.;
RT "The small GTPases Rab9A and Rab23 function at distinct steps in
RT autophagy during group A Streptococcus infection.";
RL Cell. Microbiol. 14:1149-1165(2012).
RN [15]
RP INTERACTION WITH SUFU, FUNCTION, GTPASE ACTIVITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=22365972; DOI=10.1016/j.cellsig.2012.02.004;
RA Chi S., Xie G., Liu H., Chen K., Zhang X., Li C., Xie J.;
RT "Rab23 negatively regulates Gli1 transcriptional factor in a Su(Fu)-
RT dependent manner.";
RL Cell. Signal. 24:1222-1228(2012).
RN [16]
RP VARIANTS VAL-13 DEL; ARG-40 AND ALA-101, AND VARIANT CRPT1 ARG-85.
RX PubMed=17503333; DOI=10.1086/518047;
RA Jenkins D., Seelow D., Jehee F.S., Perlyn C.A., Alonso L.G.,
RA Bueno D.F., Donnai D., Josifiova D., Mathijssen I.M.J., Morton J.E.V.,
RA Orstavik K.H., Sweeney E., Wall S.A., Marsh J.L., Nuernberg P.,
RA Passos-Bueno M.R., Wilkie A.O.M.;
RT "RAB23 mutations in Carpenter syndrome imply an unexpected role for
RT hedgehog signaling in cranial-suture development and obesity.";
RL Am. J. Hum. Genet. 80:1162-1170(2007).
RN [17]
RP VARIANTS CRPT1 LYS-12 AND TYR-79 DEL.
RX PubMed=21412941; DOI=10.1002/humu.21457;
RA Jenkins D., Baynam G., De Catte L., Elcioglu N., Gabbett M.T.,
RA Hudgins L., Hurst J.A., Jehee F.S., Oley C., Wilkie A.O.;
RT "Carpenter syndrome: extended RAB23 mutation spectrum and analysis of
RT nonsense-mediated mRNA decay.";
RL Hum. Mutat. 32:E2069-E2078(2011).
CC -!- FUNCTION: The small GTPases Rab are key regulators of
CC intracellular membrane trafficking, from the formation of
CC transport vesicles to their fusion with membranes. Rabs cycle
CC between an inactive GDP-bound form and an active GTP-bound form
CC that is able to recruit to membranes different set of downstream
CC effectors directly responsible for vesicle formation, movement,
CC tethering and fusion. Together with SUFU, prevents nuclear import
CC of GLI1, and thereby inhibits GLI1 transcription factor activity.
CC Regulates GLI1 in differentiating chondrocytes. Likewise,
CC regulates GLI3 proteolytic processing and modulates GLI2 and GLI3
CC transcription factor activity. Plays a role in autophagic vacuole
CC assembly, and mediates defense against pathogens, such as
CC S.aureus, by promoting their capture by autophagosomes that then
CC merge with lysosomes.
CC -!- SUBUNIT: Interacts with SUFU.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic
CC side (By similarity). Cell membrane. Cytoplasm. Cytoplasmic
CC vesicle, autophagosome. Endosome membrane (By similarity).
CC Cytoplasmic vesicle, phagosome. Cytoplasmic vesicle, phagosome
CC membrane; Lipid-anchor; Cytoplasmic side (By similarity).
CC Note=Recruited to phagosomes containing S.aureus or
CC M.tuberculosis.
CC -!- DISEASE: Carpenter syndrome 1 (CRPT1) [MIM:201000]: A rare
CC autosomal recessive disorder characterized by acrocephaly with
CC variable synostosis of the sagittal, lambdoid, and coronal
CC sutures; peculiar facies; brachydactyly of the hands with
CC syndactyly; preaxial polydactyly and syndactyly of the feet;
CC congenital heart defects; growth retardation; mental retardation;
CC hypogenitalism; and obesity. In addition, cerebral malformations,
CC oral and dental abnormalities, coxa valga, genu valgum,
CC hydronephrosis, precocious puberty, and hearing loss may be
CC observed. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
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DR EMBL; AB034244; BAA87324.1; -; mRNA.
DR EMBL; AB025427; BAB40309.1; -; mRNA.
DR EMBL; AF161486; AAF29101.1; -; mRNA.
DR EMBL; AF498951; AAM21099.1; -; mRNA.
DR EMBL; AK313796; BAG36532.1; -; mRNA.
DR EMBL; AY585189; AAT79492.1; -; mRNA.
DR EMBL; CR749371; CAH18224.1; -; mRNA.
DR EMBL; AL031321; CAI21564.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX04476.1; -; Genomic_DNA.
DR EMBL; BC015021; AAH15021.1; -; mRNA.
DR RefSeq; NP_001265595.1; NM_001278666.1.
DR RefSeq; NP_001265596.1; NM_001278667.1.
DR RefSeq; NP_001265597.1; NM_001278668.1.
DR RefSeq; NP_057361.3; NM_016277.4.
DR RefSeq; NP_899050.1; NM_183227.2.
DR UniGene; Hs.555016; -.
DR ProteinModelPortal; Q9ULC3; -.
DR SMR; Q9ULC3; 8-171.
DR IntAct; Q9ULC3; 3.
DR MINT; MINT-6783510; -.
DR STRING; 9606.ENSP00000320413; -.
DR PhosphoSite; Q9ULC3; -.
DR DMDM; 12643897; -.
DR PaxDb; Q9ULC3; -.
DR PRIDE; Q9ULC3; -.
DR DNASU; 51715; -.
DR Ensembl; ENST00000317483; ENSP00000320413; ENSG00000112210.
DR Ensembl; ENST00000468148; ENSP00000417610; ENSG00000112210.
DR GeneID; 51715; -.
DR KEGG; hsa:51715; -.
DR UCSC; uc003pds.3; human.
DR CTD; 51715; -.
DR GeneCards; GC06M057100; -.
DR HGNC; HGNC:14263; RAB23.
DR HPA; HPA029135; -.
DR HPA; HPA029136; -.
DR MIM; 201000; phenotype.
DR MIM; 606144; gene.
DR neXtProt; NX_Q9ULC3; -.
DR Orphanet; 65759; Carpenter syndrome.
DR PharmGKB; PA34113; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000233968; -.
DR HOVERGEN; HBG100144; -.
DR InParanoid; Q9ULC3; -.
DR KO; K06234; -.
DR OMA; VTEVFKY; -.
DR OrthoDB; EOG72C51B; -.
DR PhylomeDB; Q9ULC3; -.
DR SignaLink; Q9ULC3; -.
DR GeneWiki; RAB23; -.
DR GenomeRNAi; 51715; -.
DR NextBio; 55759; -.
DR PRO; PR:Q9ULC3; -.
DR Bgee; Q9ULC3; -.
DR CleanEx; HS_RAB23; -.
DR Genevestigator; Q9ULC3; -.
DR GO; GO:0005776; C:autophagic vacuole; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0000045; P:autophagic vacuole assembly; IMP:UniProtKB.
DR GO; GO:0006968; P:cellular defense response; IMP:UniProtKB.
DR GO; GO:0097094; P:craniofacial suture morphogenesis; IMP:UniProtKB.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0045861; P:negative regulation of proteolysis; IEA:Ensembl.
DR GO; GO:0042992; P:negative regulation of transcription factor import into nucleus; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0021513; P:spinal cord dorsal/ventral patterning; IEA:Ensembl.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR003579; Small_GTPase_Rab_type.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00449; RASTRNSFRMNG.
DR SMART; SM00175; RAB; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Complete proteome; Craniosynostosis; Cytoplasm;
KW Cytoplasmic vesicle; Developmental protein; Disease mutation;
KW Endosome; GTP-binding; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Polymorphism; Prenylation; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1 234 Ras-related protein Rab-23.
FT /FTId=PRO_0000121211.
FT PROPEP 235 237 Removed in mature form (Potential).
FT /FTId=PRO_0000370771.
FT NP_BIND 16 23 GTP (By similarity).
FT NP_BIND 64 68 GTP (By similarity).
FT NP_BIND 121 124 GTP (By similarity).
FT MOTIF 38 46 Effector region (By similarity).
FT MOD_RES 234 234 Cysteine methyl ester (Potential).
FT LIPID 234 234 S-geranylgeranyl cysteine (By
FT similarity).
FT VARIANT 12 12 M -> K (in CRPT1).
FT /FTId=VAR_065294.
FT VARIANT 13 13 Missing.
FT /FTId=VAR_034900.
FT VARIANT 40 40 K -> R (in dbSNP:rs45442500).
FT /FTId=VAR_034901.
FT VARIANT 79 79 Missing (in CRPT1).
FT /FTId=VAR_065295.
FT VARIANT 85 85 C -> R (in CRPT1).
FT /FTId=VAR_034902.
FT VARIANT 101 101 S -> A (in dbSNP:rs45479896).
FT /FTId=VAR_034903.
FT VARIANT 207 207 G -> S (in dbSNP:rs1040461).
FT /FTId=VAR_017159.
FT CONFLICT 95 95 E -> G (in Ref. 3; AAF29101).
FT CONFLICT 144 144 K -> R (in Ref. 3; AAF29101).
FT CONFLICT 225 225 K -> N (in Ref. 3; AAF29101).
SQ SEQUENCE 237 AA; 26659 MW; B9CB96E94DDF6036 CRC64;
MLEEDMEVAI KMVVVGNGAV GKSSMIQRYC KGIFTKDYKK TIGVDFLERQ IQVNDEDVRL
MLWDTAGQEE FDAITKAYYR GAQACVLVFS TTDRESFEAV SSWREKVVAE VGDIPTVLVQ
NKIDLLDDSC IKNEEAEALA KRLKLRFYRT SVKEDLNVNE VFKYLAEKYL QKLKQQIAED
PELTHSSSNK IGVFNTSGGS HSGQNSGTLN GGDVINLRPN KQRTKKNRNP FSSCSIP
//

MIM 201000
*RECORD*
*FIELD* NO
201000
*FIELD* TI
#201000 CARPENTER SYNDROME 1; CRPT1
;;CARPENTER SYNDROME;;
ACROCEPHALOPOLYSYNDACTYLY TYPE II;;
read moreACPS II
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
Carpenter syndrome-1 (CRPT1) can be caused by homozygous mutation in the
RAB23 gene (606144) on chromosome 6p11.

DESCRIPTION

Carpenter syndrome is a rare autosomal recessive disorder with the
cardinal features of acrocephaly with variable synostosis of the
sagittal, lambdoid, and coronal sutures; peculiar facies; brachydactyly
of the hands with syndactyly; preaxial polydactyly and syndactyly of the
feet; congenital heart defects; growth retardation; mental retardation;
hypogenitalism; and obesity. In addition, cerebral malformations, oral
and dental abnormalities, coxa valga, genu valgum, hydronephrosis,
precocious puberty, and hearing loss may be observed (summary by
Altunhan et al., 2011).

- Genetic Heterogeneity of Carpenter Syndrome

Carpenter syndrome-2 (CRPT2; 614976), in which the features of Carpenter
syndrome are sometimes associated with defective lateralization, is
caused by mutation in the MEGF8 gene (604267).

CLINICAL FEATURES

Carpenter (1909) described 2 sisters and a brother with acrocephaly,
peculiar facies, brachydactyly, and syndactyly in the hands, and
preaxial polydactyly and syndactyly of the toes. Temtamy (1966) could
find 9 other reported cases and added one. In older patients obesity,
mental retardation, and hypogonadism had been noted. In all cases the
parents have been normal. Parental consanguinity was suspected in 1
case.

The case of acrocephalosyndactyly with foot polydactyly reported by Owen
(1952) probably represented Carpenter syndrome, as do the sibs reported
by Schonenberg and Scheidhauer (1966). One patient thought to have this
condition by Palacios and Schimke (1969) was 49 years old. Eaton et al.
(1974) reported affected sibs.

Cohen et al. (1987) described 2 affected sibs showing marked
intrafamilial variability. This experience and a review of the
literature suggested that the Goodman syndrome (201020) and the Summitt
syndrome (272350) fall well within the clinical spectrum of the
Carpenter syndrome. Gershoni-Baruch (1990) described a brother and
sister with rather striking differences in severity. The first born had
craniosynostosis of the sagittal suture, normal intelligence, and no
abnormalities of the hands and feet. The second born sib had
polysyndactyly of hands and feet, normal intelligence, and no
craniosynostosis. Gershoni-Baruch (1990) suggested that polysyndactyly
is not an absolute requisite for the diagnosis of Carpenter syndrome and
that the Summitt and Goodman syndromes are 'within the clinical
spectrum' of Carpenter syndrome, as suggested by Cohen et al. (1987).

Alessandri et al. (2010) described 4 boys with Carpenter syndrome from a
consanguineous Comoros Islands pedigree. All 4 boys presented with
acrocephaly and polysyndactyly, but displayed variable severity of
craniosynostosis ranging from cloverleaf skull to predominant
involvement of the metopic ridge (turricephaly). All of the children
also had a combination of brachydactyly with agenesis of the middle
phalanges, syndactyly, broad thumbs, and postaxial polydactyly in the
hands, with preaxial polydactyly and syndactyly of the toes. Mental
development was normal in all; brain imaging showed hydrocephalus in 2
of the 4 boys. Additional features included corneal anomaly in 2,
cryptorchidism in 3, umbilical hernia in 1, genu valgum in 2, umbilical
hernia in 1, severe kyphoscoliosis in 1, patent ductus arteriosus in 1,
and accessory spleen in 1.

MAPPING

Using homozygosity mapping, Jenkins et al. (2007) found linkage of
Carpenter syndrome to chromosome 6p12.1-q12.

INHERITANCE

Carpenter syndrome is an autosomal recessive disorder (Jenkins et al.,
2007).

MOLECULAR GENETICS

In 15 independent families with Carpenter syndrome, Jenkins et al.
(2007) identified 5 different mutations (4 truncating and 1 missense) in
the RAB23 gene (see, e.g., L145X, 606144.0001; 606144.0002), which
encodes a member of the RAB guanosine triphosphatase (GTPase) family of
vesicle transport proteins and acts as a negative regulator of hedgehog
(HH) signaling (see 600725). In 10 patients, the disease was caused by
homozygosity for the same L145X mutation that resides on a common
haplotype, indicative of a founder effect in patients of northern
European descent.

In 4 boys with Carpenter syndrome from a consanguineous Comoros Islands
pedigree, Alessandri et al. (2010) identified homozygosity for a 1-bp
duplication in the RAB23 gene (606144.0003).

NOMENCLATURE

The designation of Carpenter syndrome as ACPS II is a relict of an
earlier classification that made the Noack syndrome ACPS I. It is now
agreed by most that Noack syndrome is the same as Pfeiffer syndrome
(101600).

*FIELD* SA
Frias et al. (1978); Pfeiffer et al. (1977); Robinson et al. (1985)
*FIELD* RF
1. Alessandri, J.-L.; Dagoneau, N.; Laville, J.-M.; Baruteau, J.;
Hebert, J.-C.; Cormier-Daire, V.: RAB23 mutation in a large family
from Comoros Islands with Carpenter syndrome. Am. J. Med. Genet. 152A:
982-986, 2010.

2. Altunhan, H.; Annagur, A.; Ors, R.: The association of Carpenter
syndrome and situs inversus totalis: first case report. Turk. Klin.
J. Med. Sci. 31: 464-467, 2011.

3. Carpenter, G.: Case of acrocephaly with other congenital malformations. Proc.
Roy. Soc. Med. 2: 45-53 and 199-201, 1909.

4. Cohen, D. M.; Green, J. G.; Miller, J.; Gorlin, R. J.; Reed, J.
A.: Acrocephalopolysyndactyly type II--Carpenter syndrome: clinical
spectrum and an attempt at unification with Goodman and Summitt syndromes. Am.
J. Med. Genet. 28: 311-324, 1987.

5. Eaton, A. P.; Sommer, A.; Kontras, S. B.; Sayers, M. P.: Carpenter
syndrome--acrocephalopolysyndactyly type II. Birth Defects Orig.
Art. Ser. 10: 249-260, 1974.

6. Frias, J. L.; Felman, A. H.; Rosenbloom, A. L.; Finkelstein, S.
N.; Hoyt, W. F.; Hall, B. D.: Normal intelligence in two children
with Carpenter syndrome. Am. J. Med. Genet. 2: 191-199, 1978.

7. Gershoni-Baruch, R.: Carpenter syndrome: marked variability of
expression to include the Summitt and Goodman syndromes. Am. J. Med.
Genet. 35: 236-240, 1990.

8. Jenkins, D.; Seelow, D.; Jehee, F. S.; Perlyn, C. A.; Alonso, L.
G.; Bueno, D. F.; Donnai, D.; Josifova, D.; Mathijssen, I. M. J.;
Morton, J. E. V.; Orstavik, K. H.; Sweeney, E.; Wall, S. A.; Marsh,
J. L.; Nurnberg, P.; Passos-Bueno, M. R.; Wilkie, A. O. M.: RAB23
mutations in Carpenter syndrome imply an unexpected role for hedgehog
signaling in cranial-suture development and obesity. Am. J. Hum.
Genet. 80: 1162-1170, 2007. Note: Erratum: Am. J. Hum. Genet. 81:
1114 only, 2007.

9. Owen, R. H.: Acrocephalosyndactyly: a case with congenital cardiac
abnormalities. Brit. J. Radiol. 25: 103-106, 1952.

10. Palacios, E.; Schimke, R. N.: Craniosynostosis--syndactylism. Am.
J. Roentgen. 106: 144-155, 1969.

11. Pfeiffer, R. A.; Seemann, K. B.; Tunte, W.; Gussone, J.; Klemm,
E.: Akrozephalopolysyndaktylie--Akrozephalosyndaktylie, Typ II McKusick
(Carpenter Syndrom): Bericht ueber 4 Faelle und eine Beobachtung des
Typs von Marshall-Smith. Klin. Paediat. 189: 120-130, 1977.

12. Robinson, L. K.; James, H. E.; Mubarak, S. J.; Allen, E. J.; Jones,
K. L.: Carpenter syndrome: natural history and clinical spectrum. Am.
J. Med. Genet. 20: 461-469, 1985.

13. Schonenberg, H.; Scheidhauer, E.: Ueber zwei ungewoehnliche Dyscranio-dysphalangien
bei Geschwistern (atypische Akrocephalosyndaktylie und fragliche Dysencephalia
splanchnocystica). Mschr. Kinderheilk. 114: 322-327, 1966.

14. Temtamy, S. A.: Carpenter's syndrome: acrocephalopolysyndactyly.
An autosomal recessive syndrome. J. Pediat. 69: 111-120, 1966.

*FIELD* CS
INHERITANCE:
Autosomal recessive

GROWTH:
[Height];
Short stature (<25th percentile);
[Weight];
Obesity

HEAD AND NECK:
[Head];
Brachycephaly;
[Face];
Midface hypoplasia;
[Ears];
Low-set ears;
Malformed ears;
Preauricular pits;
Conductive hearing loss;
Sensorineural hearing loss;
[Eyes];
Epicanthal folds;
Corneal opacity;
Microcornea;
Optic atrophy;
Lateral displacement of medial canthi;
[Nose];
Flat nasal bridge;
[Mouth];
High-arched palate;
[Teeth];
Missing teeth;
Delayed loss of deciduous teeth;
[Neck];
Short muscular neck

CARDIOVASCULAR:
[Heart];
Atrial septal defect;
Ventricular septal defect;
Pulmonic stenosis;
Tetralogy of Fallot;
[Vascular];
Transposition of great vessels;
Patent ductus arteriosus

ABDOMEN:
[External features];
Umbilical hernia;
Omphalocele;
[Spleen];
Accessory spleens

GENITOURINARY:
[Internal genitalia, male];
Cryptorchidism;
[Kidneys];
Hydronephrosis;
[Ureters];
Hydroureter

SKELETAL:
[Skull];
Craniosynostosis (coronal, sagittal, lambdoid sutures);
[Spine];
Pilonidal dimple;
Absent coccyx;
Spina bifida occulta;
Scoliosis;
[Pelvis];
Coxa valga;
Decreased hip-joint mobility;
Flared ilia;
[Limbs];
Genu valgum;
Lateral displacement of patellae;
[Hands];
Brachydactyly;
Postaxial polydactyly;
Clinodactyly;
Syndactyly;
Camptodactyly;
[Feet];
Preaxial polydactyly;
Syndactyly;
Metatarsus varus

NEUROLOGIC:
[Central nervous system];
Variable delay (IQ range 52-104)

ENDOCRINE FEATURES:
Precocious puberty

MOLECULAR BASIS:
Caused by mutation in the Ras-associated protein RAB23 gene (RAB23,
606144.0001)

*FIELD* CN
Kelly A. Przylepa - revised: 4/17/2002

*FIELD* CD
John F. Jackson: 11/12/1997

*FIELD* ED
alopez: 05/29/2007
ckniffin: 5/22/2007
joanna: 4/17/2002
joanna: 11/12/1997

*FIELD* CN
Marla J. F. O'Neill - updated: 12/10/2012
Marla J. F. O'Neill - updated: 12/1/2010
Victor A. McKusick - updated: 5/23/2007

*FIELD* CD
Victor A. McKusick: 6/2/1986

*FIELD* ED
carol: 12/10/2012
carol: 8/31/2011
wwang: 12/2/2010
terry: 12/1/2010
carol: 10/5/2007
alopez: 5/29/2007
terry: 5/23/2007
mgross: 3/17/2004
joanna: 8/4/1996
mimadm: 11/12/1995
pfoster: 3/30/1994
warfield: 3/7/1994
supermim: 3/16/1992
supermim: 3/20/1990
supermim: 3/7/1990

MIM 606144
*RECORD*
*FIELD* NO
606144
*FIELD* TI
*606144 RAS-ASSOCIATED PROTEIN RAB23; RAB23
*FIELD* TX

DESCRIPTION

Rab proteins are small GTPases of the Ras superfamily involved in the
read moreregulation of intracellular membrane trafficking. The RAB23 gene encodes
an essential negative regulator of the Sonic hedgehog (SHH; 600725)
signaling pathway. For additional background information on Rab
proteins, see 179508.

CLONING

By a map-based approach, Eggenschwiler et al. (2001) cloned the gene
mutant in the mouse 'open brain 'phenotype (opb; see later) and found
that it encodes Rab23, a member of the Rab family of vesicle transport
proteins. The human RAB23 gene encodes a 237-amino acid protein. RAB23
is 30 to 35% identical to other mammalian Rab proteins and includes all
the canonical motifs required for guanine nucleotide binding, GTP
hydrolysis, membrane association, and the conformational switch between
the GTP and GDP-bound state. Rab23 is a relatively divergent Rab protein
with an unusually long carboxy-terminal tail. In the mouse at embryonic
day 10.5, Rab23 RNA was present at low levels in most tissues, and was
present at high levels in the spinal cord, somites, limb buds, and
cranial mesenchyme. In the spinal cord, Rab23 was expressed at highest
levels in the dorsal half of the neural tube, although it was excluded
from the roof plate. In the limb bud, it was expressed in the crescent
of mesenchymal cells that are capable of responding to Shh signaling.
The expression pattern of Rab23 RNA is similar to that of Gli3 (165240),
another negative regulator of the Shh signaling pathway.

GENE STRUCTURE

The RAB23 gene contains 8 exons, and the first 2 exons are noncoding
(Alessandri et al., 2010).

MAPPING

By database searching, Zhang et al. (2000) mapped the RAB23 gene to
chromosome 6p11 based on similarity between the RAB23 sequence (GenBank
GENBANK AF161486) and previously mapped sequences.

GENE FUNCTION

Mutations in Shh and opb cause opposing transformations in neural cell
fate: Shh mutant embryos lack ventral cell types throughout the spinal
cord, whereas opb mutant embryos lack dorsal cell types specifically in
the caudal spinal cord. Eggenschwiler et al. (2001) demonstrated that
opb acts downstream of Shh. Ventral cell types that are absent in Shh
mutants, including the floor plate, are present in Shh-opb double
mutants. The organization of ventral cell types in Shh-opb double
mutants reveals that Shh-independent mechanisms can pattern the neural
tube along its dorsal-ventral axis. Eggenschwiler et al. (2001)
concluded that dorsalizing signals activate transcription of Rab23 in
order to silence the Shh pathway in dorsal neural cells.

MOLECULAR GENETICS

Carpenter syndrome (201000) is a pleiotropic disorder with autosomal
recessive inheritance, the cardinal features of which include
craniosynostosis, polysyndactyly, obesity, and cardiac defects. In 15
independent families with Carpenter syndrome, Jenkins et al. (2007)
identified 5 different mutations, including 4 truncating (see, e.g.,
L145X, 606144.0001; 606144.0002) and 1 missense, in the RAB23 gene. In
10 patients, the disease was caused by homozygosity for the same L145X
mutation that resides on a common haplotype, indicative of a founder
effect in patients of northern European descent. Nonsense mutations of
Rab23 in 'open brain' mice were found to cause recessive embryonic
lethality with neural tube defects, suggesting a species difference in
the requirement for RAB23 during early development. The discovery of
RAB23 mutations in patients with Carpenter syndrome implicated HH
signaling in cranial suture biogenesis; this was an unexpected finding
given that craniosynostosis is not usually associated with mutations of
other HH pathway components. The finding also provides a new molecular
target for studies of obesity, which is a consistent feature of
Carpenter syndrome.

In a consanguineous Comoros Islands pedigree with Carpenter syndrome,
Alessandri et al. (2010) identified homozygosity for a 1-bp duplication
in the RAB23 gene (606144.0003).

ANIMAL MODEL

Homozygous 'open brain' (opb) mice die during the second half of
gestation, with an open neural tube in the head and spinal cord,
abnormal somites, polydactyly, and poorly developed eyes (Gunther et
al., 1994). Eggenschwiler et al. (2001) found that the opb mutation
arises from the Rab23 gene. The opb1 allele encodes a lys-to-ter
mutation at codon 39; the opb2 allele encodes an arg-to-ter mutation at
codon 80. These alleles would lack the domains required for guanine
nucleotide and Rab effector binding and are therefore null alleles.

*FIELD* AV
.0001
CARPENTER SYNDROME
RAB23, LEU145TER

In 10 probands with Carpenter syndrome (201000), including 3 each from
the Netherlands and the United Kingdom, 2 from Brazil, and 1 each from
the United States and Denmark, Jenkins et al. (2007) found apparent
homozygosity 434T-A transversion in the RAB23 gene, resulting in a
leu145-to-ter (L145X) substitution. A haplotype common to all of these
cases was found and shown to contain only 8 genes in addition to RAB23.

.0002
CARPENTER SYNDROME
RAB23, 1-BP INS, 408T

In 2 Brazilian families with Carpenter syndrome (201000), 1
African/white and the other white, Jenkins et al. (2007) found
homozygosity for a 1-bp insertion in the RAB23 gene, 408-409insT,
resulting in a glu137-to-ter (E137X) change in the protein product.

.0003
CARPENTER SYNDROME
RAB23, 1-BP DUP, 86A

In 4 boys with Carpenter syndrome (201000) from a consanguineous Comoros
Islands pedigree, Alessandri et al. (2010) identified homozygosity for a
1-bp duplication (86dupA) in first coding exon of the RAB23 gene,
resulting in a premature stop codon (Y29X).

*FIELD* RF
1. Alessandri, J.-L.; Dagoneau, N.; Laville, J.-M.; Baruteau, J.;
Hebert, J.-C.; Cormier-Daire, V.: RAB23 mutation in a large family
from Comoros Islands with Carpenter syndrome. Am. J. Med. Genet. 152A:
982-986, 2010.

2. Eggenschwiler, J. T.; Espinoza, E.; Anderson, K. V.: Rab23 is
an essential negative regulator of the mouse Sonic hedgehog signalling
pathway. Nature 412: 194-198, 2001.

3. Gunther, T.; Struwe, M.; Aguzzi, A.; Schughart, K.: open brain,
a new mouse mutant with severe neural tube defects, shows altered
gene expression patterns in the developing spinal cord. Development 120:
3119-3130, 1994.

4. Jenkins, D.; Seelow, D.; Jehee, F. S.; Perlyn, C. A.; Alonso, L.
G.; Bueno, D. F.; Donnai, D.; Josifova, D.; Mathijssen, I. M. J.;
Morton, J. E. V.; Orstavik, K. H.; Sweeney, E.; Wall, S. A.; Marsh,
J. L.; Nurnberg, P.; Passos-Bueno, M. R.; Wilkie, A. O. M.: RAB23
mutations in Carpenter syndrome imply an unexpected role for hedgehog
signaling in cranial-suture development and obesity. Am. J. Hum.
Genet. 80: 1162-1170, 2007. Note: Erratum: Am. J. Hum. Genet. 81:
1114 only, 2007.

5. Zhang, Q.-H.; Ye, M.; Wu, X.-Y.; Ren, S.-X.; Zhao, M.; Zhao, C.-J.;
Fu, G.; Shen, Y.; Fan, H.-Y.; Lu, G.; Zhong, M.; Xu, X.-R.; and 9
others: Cloning and functional analysis of cDNAs with open reading
frames for 300 previously undefined genes expressed in CD34+ hematopoietic
stem/progenitor cells. Genome Res. 10: 1546-1560, 2000.

*FIELD* CN
Marla J. F. O'Neill - updated: 12/1/2010
Victor A. McKusick - updated: 5/23/2007

*FIELD* CD
Ada Hamosh: 7/23/2001

*FIELD* ED
wwang: 12/02/2010
terry: 12/1/2010
carol: 10/5/2007
alopez: 5/29/2007
terry: 5/23/2007
mcapotos: 12/27/2001
alopez: 7/24/2001

RBCC Red Blood Cell Collection

Full text data of RAB23