RBCC

Full text data of VPS33B

VPS33B [Confidence: low (only semi-automatic identification from reviews)]
Vacuolar protein sorting-associated protein 33B; hVPS33B

UniProt Q9H267
ID VP33B_HUMAN Reviewed; 617 AA.
AC Q9H267; Q96K14; Q9NRP6; Q9NSF3;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-NOV-2010, sequence version 2.
DT 22-JAN-2014, entry version 116.
DE RecName: Full=Vacuolar protein sorting-associated protein 33B;
DE Short=hVPS33B;
GN Name=VPS33B;
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], AND VARIANT SER-514.
RX PubMed=10894945;
RA Carim-Todd L., Sumoy L., Andreu N., Estivill X., Escarceller M.;
RT "Cloning, mapping and expression analysis of VPS33B, the human
RT orthologue of rat Vps33b.";
RL Cytogenet. Cell Genet. 89:92-95(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11250079; DOI=10.1016/S0378-1119(01)00333-X;
RA Huizing M., Didier A., Walenta J., Anikster Y., Gahl W.A., Kraemer H.;
RT "Molecular cloning and characterization of human VPS18, VPS11, VPS16,
RT and VPS33.";
RL Gene 264:241-247(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-514.
RC TISSUE=Placenta;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-514.
RC TISSUE=Placenta;
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 [6]
RP FUNCTION, DEPHOSPHORYLATION, PHOSPHORYLATION, INTERACTION WITH
RP MYCOBACTERIUM TUBERCULOSIS PTPA, MUTAGENESIS OF TYR-133; TYR-382;
RP TYR-511 AND TYR-517, SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RX PubMed=18474358; DOI=10.1016/j.chom.2008.03.008;
RA Bach H., Papavinasasundaram K.G., Wong D., Hmama Z., Av-Gay Y.;
RT "Mycobacterium tuberculosis virulence is mediated by PtpA
RT dephosphorylation of human vacuolar protein sorting 33B.";
RL Cell Host Microbe 3:316-322(2008).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP INTERACTION WITH RAB11A AND VIPAS39, CHARACTERIZATION OF VARIANT ARCS1
RP PRO-30, AND SUBCELLULAR LOCATION.
RX PubMed=20190753; DOI=10.1038/ng.538;
RA Cullinane A.R., Straatman-Iwanowska A., Zaucker A., Wakabayashi Y.,
RA Bruce C.K., Luo G., Rahman F., Gurakan F., Utine E., Ozkan T.B.,
RA Denecke J., Vukovic J., Di Rocco M., Mandel H., Cangul H.,
RA Matthews R.P., Thomas S.G., Rappoport J.Z., Arias I.M., Wolburg H.,
RA Knisely A.S., Kelly D.A., Muller F., Maher E.R., Gissen P.;
RT "Mutations in VIPAR cause an arthrogryposis, renal dysfunction and
RT cholestasis syndrome phenotype with defects in epithelial
RT polarization.";
RL Nat. Genet. 42:303-312(2010).
RN [9]
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 [10]
RP VARIANT ARCS1 PRO-30, AND SUBCELLULAR LOCATION.
RX PubMed=15052268; DOI=10.1038/ng1325;
RA Gissen P., Johnson C.A., Morgan N.V., Stapelbroek J.M., Forshew T.,
RA Cooper W.N., McKiernan P.J., Klomp L.W.J., Morris A.A.M., Wraith J.E.,
RA McClean P., Lynch S.A., Thompson R.J., Lo B., Quarrell O.W.,
RA Di Rocco M., Trembath R.C., Mandel H., Wali S., Karet F.E.,
RA Knisely A.S., Houwen R.H.J., Kelly D.A., Maher E.R.;
RT "Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane
RT fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC)
RT syndrome.";
RL Nat. Genet. 36:400-404(2004).
RN [11]
RP VARIANT ARCS1 PHE-243.
RX PubMed=18853461; DOI=10.1002/humu.20900;
RA Cullinane A.R., Straatman-Iwanowska A., Seo J.K., Ko J.S., Song K.S.,
RA Gizewska M., Gruszfeld D., Gliwicz D., Tuysuz B., Erdemir G.,
RA Sougrat R., Wakabayashi Y., Hinds R., Barnicoat A., Mandel H.,
RA Chitayat D., Fischler B., Garcia-Cazorla A., Knisely A.S., Kelly D.A.,
RA Maher E.R., Gissen P.;
RT "Molecular investigations to improve diagnostic accuracy in patients
RT with ARC syndrome.";
RL Hum. Mutat. 30:E330-E337(2009).
CC -!- FUNCTION: May play a role in vesicle-mediated protein trafficking
CC to lysosomal compartments and in membrane docking/fusion reactions
CC of late endosomes/lysosomes. Mediates phagolysosomal fusion in
CC macrophages.
CC -!- SUBUNIT: Interacts with RAB11A and VIPAS39. Interacts with
CC M.tuberculosis PtpA.
CC -!- INTERACTION:
CC Q9H9C1:VIPAS39; NbExp=20; IntAct=EBI-749072, EBI-749080;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane; Peripheral membrane
CC protein; Cytoplasmic side. Lysosome membrane; Peripheral membrane
CC protein; Cytoplasmic side. Note=Cytoplasmic, peripheral membrane
CC protein associated with late endosomes/lysosomes. Colocalizes with
CC M.tuberculosis PtpA in the cytosol of tuberculosis-infected
CC macrophages and associates with phagosomes. Colocalizes in
CC clusters with VIPAS39 at cytoplasmic organelles.
CC -!- TISSUE SPECIFICITY: Ubiquitous; highly expressed in testis and low
CC expression in the lung.
CC -!- PTM: Phosphorylated on tyrosine residues. Dephosphorylation by
CC M.tuberculosis PtpA is necessary to induce the reduction of host
CC phagolysosome fusion in M.tuberculosis-infected macrophages.
CC -!- DISEASE: Arthrogryposis, renal dysfunction and cholestasis
CC syndrome 1 (ARCS1) [MIM:208085]: A multisystem disorder,
CC characterized by neurogenic arthrogryposis multiplex congenita,
CC renal tubular dysfunction and neonatal cholestasis with bile duct
CC hypoplasia and low gamma glutamyl transpeptidase activity.
CC Platelet dysfunction is common. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the STXBP/unc-18/SEC1 family.
CC -!- CAUTION: According to PubMed:18474358, it is autophosphorylated.
CC However, it is not related with protein kinases, suggesting it is
CC phosphorylated by another protein.
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DR EMBL; AF201694; AAF91174.1; -; mRNA.
DR EMBL; AL357472; CAB93109.1; -; mRNA.
DR EMBL; AF308803; AAG34680.1; -; mRNA.
DR EMBL; AK027754; BAB55345.1; -; mRNA.
DR EMBL; AC068831; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016445; AAH16445.1; -; mRNA.
DR RefSeq; NP_061138.3; NM_018668.3.
DR UniGene; Hs.745007; -.
DR ProteinModelPortal; Q9H267; -.
DR SMR; Q9H267; 14-614.
DR IntAct; Q9H267; 8.
DR MINT; MINT-1451069; -.
DR STRING; 9606.ENSP00000327650; -.
DR PhosphoSite; Q9H267; -.
DR DMDM; 23396926; -.
DR PaxDb; Q9H267; -.
DR PRIDE; Q9H267; -.
DR Ensembl; ENST00000333371; ENSP00000327650; ENSG00000184056.
DR GeneID; 26276; -.
DR KEGG; hsa:26276; -.
DR UCSC; uc002bqp.1; human.
DR CTD; 26276; -.
DR GeneCards; GC15M091541; -.
DR H-InvDB; HIX0202153; -.
DR HGNC; HGNC:12712; VPS33B.
DR HPA; HPA040415; -.
DR MIM; 208085; phenotype.
DR MIM; 608552; gene.
DR neXtProt; NX_Q9H267; -.
DR Orphanet; 2697; Arthrogryposis - renal dysfunction - cholestasis.
DR PharmGKB; PA37327; -.
DR eggNOG; COG5158; -.
DR HOGENOM; HOG000166771; -.
DR HOVERGEN; HBG106182; -.
DR InParanoid; Q9H267; -.
DR OMA; KGYRFIF; -.
DR OrthoDB; EOG722J85; -.
DR PhylomeDB; Q9H267; -.
DR GeneWiki; VPS33B; -.
DR GenomeRNAi; 26276; -.
DR NextBio; 48583; -.
DR PRO; PR:Q9H267; -.
DR ArrayExpress; Q9H267; -.
DR Bgee; Q9H267; -.
DR CleanEx; HS_VPS33B; -.
DR Genevestigator; Q9H267; -.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0031091; C:platelet alpha granule; IDA:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; IDA:UniProtKB.
DR GO; GO:0032400; P:melanosome localization; IDA:UniProtKB.
DR GO; GO:0061025; P:membrane fusion; IMP:UniProtKB.
DR GO; GO:0070889; P:platelet alpha granule organization; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IMP:UniProtKB.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; IEA:InterPro.
DR GO; GO:0016192; P:vesicle-mediated transport; IDA:MGI.
DR Gene3D; 3.40.50.1910; -; 2.
DR InterPro; IPR027482; Sec-1-like_dom2.
DR InterPro; IPR001619; Sec1-like.
DR InterPro; IPR027121; VPS33.
DR PANTHER; PTHR11679; PTHR11679; 1.
DR PANTHER; PTHR11679:SF1; PTHR11679:SF1; 1.
DR Pfam; PF00995; Sec1; 1.
DR SUPFAM; SSF56815; SSF56815; 2.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Disease mutation; Endosome; Lysosome;
KW Membrane; Phosphoprotein; Polymorphism; Protein transport;
KW Reference proteome; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 617 Vacuolar protein sorting-associated
FT protein 33B.
FT /FTId=PRO_0000206305.
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 30 30 L -> P (in ARCS1; interacts with VIPAS39
FT but does not colocalize with VIPAS39 at
FT cytoplasmic organelles).
FT /FTId=VAR_018983.
FT VARIANT 243 243 S -> F (in ARCS1).
FT /FTId=VAR_057901.
FT VARIANT 513 513 F -> S (in dbSNP:rs3177428).
FT /FTId=VAR_057330.
FT VARIANT 514 514 G -> S (in dbSNP:rs11073964).
FT /FTId=VAR_013828.
FT MUTAGEN 133 133 Y->E: Reduces phosphorylation activity,
FT but does not impair phagolysosomal fusion
FT in M.tuberculosis-infected macrophages;
FT when associated with E-382; E-511 and E-
FT 517.
FT MUTAGEN 382 382 Y->E: Reduces phosphorylation activity,
FT but does not impair phagolysosomal fusion
FT in M.tuberculosis-infected macrophages;
FT when associated with E-133; E-511 and E-
FT 517.
FT MUTAGEN 511 511 Y->E: Reduces phosphorylation activity,
FT but does not impair phagolysosomal fusion
FT in M.tuberculosis-infected macrophages;
FT when associated with E-133; E-382 and E-
FT 517.
FT MUTAGEN 517 517 Y->E: Reduces phosphorylation activity,
FT but does not impair phagolysosomal fusion
FT in M.tuberculosis-infected macrophages;
FT when associated with E-133; E-382 and E-
FT 511.
FT CONFLICT 293 293 H -> Y (in Ref. 3; BAB55345).
FT CONFLICT 466 466 K -> E (in Ref. 3; BAB55345).
SQ SEQUENCE 617 AA; 70585 MW; BD7DB97E1FEB1D32 CRC64;
MAFPHRPDAP ELPDFSMLKR LARDQLIYLL EQLPGKKDLF IEADLMSPLD RIANVSILKQ
HEVDKLYKVE NKPALSSNEQ LCFLVRPRIK NMRYIASLVN ADKLAGRTRK YKVIFSPQKF
YACEMVLEEE GIYGDVSCDE WAFSLLPLDV DLLSMELPEF FRDYFLEGDQ RWINTVAQAL
HLLSTLYGPF PNCYGIGRCA KMAYELWRNL EEEEDGETKG RRPEIGHIFL LDRDVDFVTA
LCSQVVYEGL VDDTFRIKCG SVDFGPEVTS SDKSLKVLLN AEDKVFNEIR NEHFSNVFGF
LSQKARNLQA QYDRRRGMDI KQMKNFVSQE LKGLKQEHRL LSLHIGACES IMKKKTKQDF
QELIKTEHAL LEGFNIREST SYIEEHIDRQ VSPIESLRLM CLLSITENGL IPKDYRSLKT
QYLQSYGPEH LLTFSNLRRA GLLTEQAPGD TLTAVESKVS KLVTDKAAGK ITDAFSSLAK
RSNFRAISKK LNLIPRVDGE YDLKVPRDMA YVFGGAYVPL SCRIIEQVLE RRSWQGLDEV
VRLLNCSDFA FTDMTKEDKA SSESLRLILV VFLGGCTFSE ISALRFLGRE KGYRFIFLTT
AVTNSARLME AMSEVKA
//

MIM 208085
*RECORD*
*FIELD* NO
208085
*FIELD* TI
#208085 ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 1; ARCS1
;;ARC SYNDROME; ARCS
read more*FIELD* TX
A number sign (#) is used with this entry because arthrogryposis, renal
dysfunction, and cholestasis-1 (ARCS1) is caused by homozygous or
compound heterozygous mutation in the VPS33B gene (608552) on chromosome
15q21.6.

Another form of arthrogryposis, renal dysfunction, and cholestasis,
ARCS2 (613404), is caused by mutation in the VIPAR gene on chromosome
14q24.3 (613401).

CLINICAL FEATURES

In 4 male sibs from a sibship of 7 of North African descent, Nezelof et
al. (1979) observed arthrogryposis multiplex congenita with jaundice and
renal dysfunction. Death occurred at 2 months, 12 days, 22 days and 42
weeks of age. Autopsy showed rarefaction of the anterior horn of the
spinal cord, renal tubular cell degeneration with nephrocalcinosis, and
abundant pigmentary deposits in the liver which gave it a grossly black
color similar to that of the Dubin-Johnson syndrome (237500). In the
mother's family, 8 other males had died at birth or shortly thereafter,
suggesting X-linked recessive inheritance to the authors.

Mikati et al. (1984) and Mikati (2007) described 2 Lebanese brothers
with proximal renal tubular insufficiency, cholestatic jaundice,
predisposition to infection, and multiple congenital anomalies.
Dysmorphic features included micrognathia, low-set ears, high-arched
palate, barrel-shaped chest, bilateral simian creases, clubfeet, and
congenital hip dislocation. They both had conjugated hyperbilirubinemia,
repeated infections, severe failure to thrive, and right ventricular
hypertrophy. Liver biopsy revealed paucity of bile ducts, bile stasis,
and some inflammatory cell infiltration. Immunologic investigation
suggested a defect in polymorphonuclear cell migration and intracellular
killing. Both died before 4 months of age.

Di Rocco et al. (1990) reported another family in which the second-born
child of first-cousin parents had arthrogryposis, cholestatic liver
disease, and renal dysfunction. The child died at age 2 months, and
autopsy showed pigmentary storage disease in liver cells,
nephrocalcinosis, and rarefaction of the motor neuron cells in the
anterior horns of the spinal cord. The family of Di Rocco et al. (1990)
is, of course, consistent with either autosomal recessive or X-linked
recessive inheritance.

Horslen et al. (1994) described 3 cases from 2 unrelated families and
reviewed 10 other cases from the literature. The association of
arthrogryposis multiplex congenita, cholestatic jaundice, and renal
Fanconi syndrome was first reported by Lutz-Richner and Landolt (1973).
Of the 13 cases, including their own, Horslen et al. (1994) found that
all of the parents were consanguineous and that all of the patients were
male except for a single patient reported by Saraiva et al. (1990). All
patients died in the first months of life. Although it had been claimed
that there were 2 separate forms of this disorder, one with a paucity of
intrahepatic bile ducts and giant cell transformation of hepatocytes and
the other with pigment deposition in liver cells and marked cholestasis,
Horslen et al. (1994) proposed, based on the histologic findings in one
of their cases, that all cases represent variation within a single
disorder.

The disorder reported in entry 210550 (biliary malformation with renal
tubular insufficiency) may represent the ARC syndrome. Di Rocco et al.
(1995) described 2 new families and compared clinical and pathologic
findings of 5 patients from 3 Italian families with other reported
cases. They proposed that all the patients reported to that time
represented a single syndrome.

Abu-Sa'da et al. (2005) reported 2 infants from different consanguineous
Saudi families with lethal ARC syndrome. Common clinical features
included failure to thrive, jaundice, ichthyosis, generalized
arthrogryposis, and hypotonia. Laboratory studies showed conjugated
bilirubinemia, metabolic acidosis, and renal tubular dysfunction with
Fanconi syndrome. One of the patients had nephrocalcinosis, nephrogenic
diabetes insipidus, and lissencephaly. They died at ages 7 and 3 months,
respectively. Abu-Sa'da et al. (2005) provided a review of the
literature on ARC syndrome and noted the variability of symptoms.

Gissen et al. (2006) characterized clinical features of 62 individuals
with ARCS from 35 families (11 of which had previously been reported).
In addition to classic features previously described, all patients had
severe failure to thrive that was not adequately explained by the degree
of liver disease, and 10% had structural cardiac defects. Almost half of
patients who underwent diagnostic organ biopsy (7 of 16 patients)
developed life-threatening hemorrhage, and most patients (9 of 11) who
suffered severe hemorrhage (7 post-biopsy and 4 spontaneous) had normal
platelet count and morphology.

Smith et al. (2012) studied an unrelated boy and girl who both had
relatively mild ARCS. The boy, who was of nonconsanguineous Peruvian and
Puerto Rican descent, exhibited failure to thrive, developmental delay
with sensorineural hearing loss, renal loss of protein and amino acids,
bilateral talipes with osteopenia, and mild cholestasis. MRI showed
dysmorphic ventricles with coaptation of the occipital horns and
irregular lateral-ventricular marginal contours. Refractory pruritus and
ichthyosis were associated with increased serum concentrations of bile
acids; the pruritus responded to cutaneous biliary diversion at 3 years
of age. At 5.5 years of age, the boy had severe hyperkeratosis and
lichenification of hand skin that interfered with fine motor tasks,
including using sign language. He had osteopenia with shortening of the
proximal fibula, generalized aminoaciduria and nephrotic-range
proteinuria, and recurrent episodes of epistaxis associated with the
absence of platelet alpha-granules. The girl, who was born to Puerto
Rican and Jualisco Mexican parents, was diagnosed with arthrogryposis
and failure to thrive at 2 weeks of age. She had renal tubular
dysfunction, mild cholestasis, hyperpigmented lichenified skin,
bilateral hip dislocations, decreased muscle bulk, and sensorineural
hearing loss. MRI at 14 months showed a thin corpus callosum and diffuse
paucity of white matter. Additional features included weak dental enamel
and easily chipped teeth.

INHERITANCE

Because of the exclusive involvement of males in early reports of this
disorder and the finding in the family reported by Nezelof et al. (1979)
of a large number of males on the mother's side of the family who had
died at birth or shortly thereafter, this disorder had been classified
as X-linked recessive. The occurrence of a female case and the universal
occurrence of parental consanguinity is strong support for autosomal
recessive inheritance.

MOLECULAR GENETICS

To elucidate the molecular basis of ARCS, Gissen et al. (2004) mapped
the disorder to a 7-cM interval on 15q26.1 and identified germline
mutations in the gene VPS33B (see, e.g., 608552.0001-608552.0003) in 14
kindreds with ARC. VPS33B encodes a homolog of the class C yeast
vacuolar protein sorting protein, Vps33, that contains a Sec1-like
domain important in the regulation of vesicle-to-target SNARE complex
formation and subsequent membrane fusion.

Gissen et al. (2006) characterized molecular features of 62 individuals
with ARCS from 35 families (11 of which had been previously reported).
Germline VPS33B mutations were present in 28 of 35 families (48 of 62
individuals); heterozygosity was found in the VPS33B locus in some cases
of ARCS, suggesting the possibility of a second ARC syndrome gene.
Gissen et al. (2006) concluded that VPS33B analysis should replace organ
biopsy as a first-line diagnostic test for ARC syndrome.

In a male infant, born of first-cousin Saudi Arabian parents, with
contracture deformities and multiple bone fractures at birth, Taha et
al. (2007) identified compound heterozygosity for the known R438X
mutation (608552.0002) and a splice site mutation (608552.0004) in the
VPS33B gene. The authors commented that presentation of ARC syndrome
with osteopenia and fractures at birth is unusual and can be misleading
during the neonatal period when other components of the syndrome may not
be evident; they also noted that compound heterozygosity is a very rare
finding in a child of consanguineous parents.

In an unrelated boy and girl with relatively mild ARCS, Smith et al.
(2012) identified compound heterozygosity for a splice site mutation in
the VPS33B gene (608552.0005) and 2 different frameshift mutations
(608552.0006 and 608552.0007, respectively). In transfection studies
with co-overexpression of VIPAR (613401) and a VPS33B missense mutation
(L30P; 608552.0003) that is associated with a more severe ARCS
phenotype, Smith et al. (2012) observed no colocalization; however, in
studies of VIPAR and the VPS33B splice site mutation, there was evidence
for aggregates containing both VPS33B and VIPAR, suggesting that some of
the function of the VPS33B-VIPAR complex might be retained with the
splice site mutation.

*FIELD* RF
1. Abu-Sa'da, O.; Barbar, M.; Al-Harbi, N.; Taha, D.: Arthrogryposis,
renal tubular acidosis and cholestasis (ARC) syndrome: two new cases
and review. Clin. Dysmorph. 14: 191-196, 2005.

2. Di Rocco, M.; Callea, F.; Pollice, B.; Faraci, M.; Campiani, F.;
Borrone, C.: Arthrogryposis, renal dysfunction and cholestasis syndrome:
report of five patients from three Italian families. Europ. J. Pediat. 154:
835-839, 1995.

3. Di Rocco, M.; Reboa, E.; Barabino, A.; Larnaout, A.; Canepa, M.;
Savioli, C.; Cremonte, M.; Borrone, C.: Arthrogryposis, cholestatic
pigmentary liver disease and renal dysfunction: report of a second
family. Am. J. Med. Genet. 37: 237-240, 1990.

4. Gissen, P.; Johnson, C. A.; Morgan, N. V.; Stapelbroek, J. M.;
Forshew, T.; Cooper, W. N.; McKiernan, P. J.; Klomp, L. W. J.; Morris,
A. A. M.; Wraith, J. E.; McClean, P.; Lynch, S. A.; and 12 others
: Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane
fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome. Nature
Genet. 36: 400-404, 2004.

5. Gissen, P.; Tee, L.; Johnson, C. A.; Genin, E.; Caliebe, A.; Chitayat,
D.; Clericuzio, C.; Denecke, J.; Di Rocco, M.; Fischler, B.; FitzPatrick,
D.; Garcia-Cazorla, A.; and 9 others: Clinical and molecular genetic
features of ARC syndrome. Hum. Genet. 120: 396-409, 2006.

6. Horslen, S. P.; Quarrell, O. W. J.; Tanner, M. S.: Liver histology
in the arthrogryposis multiplex congenita, renal dysfunction, and
cholestasis (ARC) syndrome: report of three new cases and review. J.
Med. Genet. 31: 62-64, 1994.

7. Lutz-Richner, A. R.; Landolt, R. F.: Familiaere Gallengangmissbildungen
mit tubulaerer Niereninsuffizienz. Helv. Paediat. Acta 28: 1-12,
1973.

8. Mikati, M. A.: Arthrogryposis, renal tubular acidosis and cholestasis
syndrome: spectrum of the clinical manifestations. (Letter) Clin.
Dysmorph. 16: 71 only, 2007.

9. Mikati, M. A.; Barakat, A. Y.; Sulh, H. B.; Der Kaloustian, V.
M.: Renal tubular insufficiency, cholestatic jaundice, and multiple
congenital anomalies--a new multisystem syndrome. Helv. Paediat.
Acta 39: 463-471, 1984.

10. Nezelof, C.; Dupart, M. C.; Jaubert, F.; Eliachar, E.: A lethal
familial syndrome associating arthrogryposis multiplex congenita,
renal dysfunction, and a cholestatic and pigmentary liver disease. J.
Pediat. 94: 258-260, 1979.

11. Saraiva, J. M.; Lemos, C.; Goncalves, I.; Carneiro, F.; Mota,
H. C.: Arthrogryposis multiplex congenita with renal and hepatic
abnormalities in a female infant. J. Pediat. 117: 761-763, 1990.

12. Smith, H.; Galmes, R.; Gogolina, E.; Straatman-Iwanowska, A.;
Reay, K.; Banushi, B.; Bruce, C. K.; Cullinane, A. R.; Romero, R.;
Chang, R.; Ackermann, O.; Baumann, C.; and 12 others: Associations
among genotype, clinical phenotype, and intracellular localization
of trafficking proteins in ARC syndrome. Hum. Mutat. 33: 1656-1664,
2012.

13. Taha, D.; Khider, A.; Cullinane, A. R.; Gissen, P.: A novel VPS33B
mutation in an ARC syndrome patient presenting with osteopenia and
fractures at birth. (Letter) Am. J. Med. Genet. 143A: 2835-2837,
2007.

*FIELD* CS
INHERITANCE:
Autosomal recessive

GROWTH:
[Other];
Failure to thrive

HEAD AND NECK:
[Head];
Microcephaly;
[Face];
Sloping forehead;
Micrognathia;
[Ears];
Low-set ears

CARDIOVASCULAR:
[Heart];
Structural cardiac defects (uncommon);
Atrial septal defects;
Ventricular septal defects;
Persistent foramen ovale;
Right ventricular hypertrophy (reported in 2 sibs)

ABDOMEN:
[Liver];
Cholestatic liver disease;
Bile duct abnormalities (paucity, proliferation);
Giant cell hepatitis;
Pigmentary deposits;
Portal tract fibrosis

GENITOURINARY:
[Kidneys];
Renal tubular acidosis;
Fanconi syndrome;
Nephropathy;
Nephrocalcinosis;
Nephrogenic diabetes insipidus (less common);
Renal tubular degeneration

SKELETAL:
Arthrogryposis multiplex congenita;
Fractures at birth;
[Pelvis];
Hip dysplasia;
[Feet];
Talipes calcaneovalgus

SKIN, NAILS, HAIR:
[Skin];
Ichthyosis;
Jaundice

NEUROLOGIC:
[Central nervous system];
Global developmental delay;
Hypotonia;
Lissencephaly (reported in 1 patient)

METABOLIC FEATURES:
Metabolic acidosis

HEMATOLOGY:
Severe bleeding after biopsies (uncommon)

IMMUNOLOGY:
Recurrent febrile illnesses;
B and T cell defects (reported in 2 sibs)

LABORATORY ABNORMALITIES:
Conjugated hyperbilirubinemia;
Abnormal liver function tests

MISCELLANEOUS:
Death in infancy, usually from sepsis, dehydration, or acidosis

MOLECULAR BASIS:
Caused by mutation in the yeast homolog, B, of the vacuolar protein
sorting 33 gene (VPS33B, 608552.0001)

*FIELD* CN
Cassandra L. Kniffin - revised: 2/13/2009

*FIELD* CD
John F. Jackson: 6/15/1995

*FIELD* ED
joanna: 01/05/2010
ckniffin: 2/13/2009
alopez: 4/6/2004

*FIELD* CN
Marla J. F. O'Neill - updated: 11/19/2013
Marla J. F. O'Neill - updated: 5/13/2010
Cassandra L. Kniffin - updated: 2/13/2009
Marla J. F. O'Neill - updated: 4/24/2008
Marla J. F. O'Neill - updated: 2/15/2007
Victor A. McKusick - updated: 4/5/2004
Victor A. McKusick - updated: 5/13/1997

*FIELD* CD
Victor A. McKusick: 4/4/1994

*FIELD* ED
carol: 11/19/2013
mcolton: 11/15/2013
carol: 8/22/2011
carol: 5/13/2010
wwang: 4/16/2009
ckniffin: 2/13/2009
wwang: 4/28/2008
terry: 4/24/2008
wwang: 2/15/2007
alopez: 4/6/2004
terry: 4/5/2004
terry: 7/9/1997
jenny: 5/13/1997
terry: 5/7/1997
carol: 4/4/1994

MIM 608552
*RECORD*
*FIELD* NO
608552
*FIELD* TI
*608552 VACUOLAR PROTEIN SORTING 33, YEAST, HOMOLOG OF, B; VPS33B
*FIELD* TX

DESCRIPTION
read more
In yeast, the Vps proteins are involved in Golgi-to-lysosome
trafficking. Mutations in class C Vps proteins, which includes Vps33,
result in the most severe vacuolar protein sorting and morphology
defects (Carim et al., 2000).

CLONING

By examining an EST cluster, database analysis, and 5-prime RACE of an
adult heart cDNA library, Carim et al. (2000) cloned full-length VPS33B.
The deduced 617-amino acid protein has a calculated molecular mass of
70.6 kD. VPS33B shares 96% amino acid identity with rat Vps33b.
Homologous proteins were identified in insect, nematode, plant, and
yeast databases. Northern blot analysis of 8 tissues detected VPS33B
mRNA above the 2.4-kb marker. VPS33B was highly enriched in testis and
less abundant in all other tissues.

By searching an EST database for sequences similar to rat Vps33, Huizing
et al. (2001) identified VPS33B. The deduced protein contains a SEC1
domain at amino acids 105 to 612, and it is likely a cytosolic protein.
Northern blot analysis detected a 2.6-kb VPS33B mRNA in all tissues
examined, including heart, brain, placenta, lung, liver, skeletal
muscle, kidney, and pancreas; lowest expression was in lung.

GENE STRUCTURE

Huizing et al. (2001) determined that the VPS33B gene spans about 2.6
kb.

MAPPING

By radiation hybrid analysis, Carim et al. (2000) mapped the VPS33B gene
to chromosome 15q26.1.

GENE FUNCTION

In a yeast 2-hybrid screen to identify VPS33B-interacting proteins,
Cullinane et al. (2010) identified 18 candidates prioritized by
bioinformatic analyses of homology and putative function. A protein
encoded by C14ORF133, which they designated VIPAR (613401), had highest
priority. Coimmunoprecipitation studies in transfected HEK293 cells
confirmed the interaction between overexpressed VPS33B and VIPAR, with
formation of functional VPS33B-VIPAR complexes at cytoplasmic organelles
that interacted with RAB11A (605570). Knockdown of vipar in zebrafish
resulted in biliary excretion and E-cadherin (CDH1; 192090) defects
similar to those in individuals with ARC syndrome (see ARCS1, 208085)
caused by mutation in VPS33B (see MOLECULAR GENETICS section) or VIPAR.
Vipar- and Vps33b-deficient mouse inner medullary collecting duct
(mIMCD-3) cells expressed membrane proteins abnormally and had
structural and functional tight junction defects. Abnormal Ceacam5
(114890) expression was due to missorting toward lysosomal degradation,
but reduced E-cadherin levels were associated with transcriptional
downregulation. Cullinane et al. (2010) concluded that the VPS33B-VIPAR
complex has diverse functions in the pathways regulating
apical-basolateral polarity in the liver and kidney.

MOLECULAR GENETICS

Gissen et al. (2004) identified mutations in the VPS33B gene as the
cause of the arthrogryposis-renal dysfunction-cholestasis syndrome
(ARCS1; 208085). VPS33B encodes a homolog of the class C yeast vacuolar
protein sorting protein gene, Vps33, which contains a Sec1-like domain
important in the regulation of vesicle-to-target SNARE complex formation
and subsequent membrane fusion. Clinical features of ARCS--renal tubular
abnormalities, cholestasis, hypotonia, and platelet storage pool
deficiency--are consistent with abnormal intracellular protein
trafficking and defective membrane fusion mechanisms in the kidneys,
liver, nervous system, and platelets, respectively.

Gissen et al. (2006) characterized clinical and molecular features of 62
individuals with ARCS from 35 families (11 of which had been previously
reported). Germline VPS33B mutations were present in 28 of 35 families
(48 of 62 individuals). Heterozygosity was found in the VPS33B locus in
some cases of ARCS, suggesting the possibility of a second ARCS gene.

In a male infant with ARCS1, born of first-cousin Saudi Arabian parents,
Taha et al. (2007) identified compound heterozygosity for the known
R438X mutation (608552.0002) and a splice site mutation (608552.0004) in
the VPS33B gene. The authors noted that compound heterozygosity is an
unusual finding in a child of consanguineous parents.

In an unrelated boy and girl with relatively mild ARCS, Smith et al.
(2012) identified compound heterozygosity for a splice site mutation in
the VPS33B gene (608552.0005) and 2 different frameshift mutations
(608552.0006 and 608552.0007, respectively). In transfection studies
with co-overexpression of VIPAR and a VPS33B missense mutation (L30P;
608552.0003) that is associated with a more severe ARCS phenotype, Smith
et al. (2012) observed no colocalization; however, in studies of VIPAR
and the VPS33B splice site mutation, there was evidence for aggregates
containing both VPS33B and VIPAR, suggesting that some of the function
of the VPS33B-VIPAR complex might be retained with the splice site
mutation.

*FIELD* AV
.0001
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 1
VPS33B, ARG532TER

In a consanguineous Pakistani family with arthrogryposis, renal
dysfunction, and cholestasis-1 (208085), Gissen et al. (2004) identified
a homozygous 1593C-T transition in the VPS33B gene resulting in an
arg532-to-ter (R532X) mutation.

.0002
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 1
VPS33B, ARG438TER

In 7 apparently unrelated consanguineous families of Pakistani origin
with arthrogryposis, renal dysfunction, and cholestasis-1 (208085),
Gissen et al. (2004) identified a homozygous 1311C-T transition in the
VPS33B gene resulting in an arg438-to-ter (R438X) mutation. Phenotype
data in these families gave evidence for a common haplotype, suggestive
of founder effect. Clinical data on some of these families were
presented by Eastham et al. (2001) and Horslen et al. (1994).

Gissen et al. (2006) characterized clinical and molecular features of 62
individuals with ARCS from 35 families (11 of which had been previously
reported). The R438X mutation was identified in 12 U.K. Pakistani
kindreds. Haplotyping in 8 unrelated patients was consistent with a
founder mutation, with the most recent common ancestor 900 to 1,000
years ago.

In a male infant, born of first-cousin Saudi Arabian parents, with
contracture deformities and multiple bone fractures at birth, Taha et
al. (2007) identified compound heterozygosity for R438X and a 700+1G-A
splice site mutation in intron 9 of the VPS33B gene (608552.0004). The
splice site mutation was inherited from one of his parents; the other
was unavailable for DNA analysis.

.0003
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 1
VPS33B, LEU30PRO

In a consanguineous family of Pakistani origin with arthrogryposis,
renal dysfunction, and cholestasis-1 (208085), Gissen et al. (2004)
identified a homozygous 89T-C transition in the VPS33B gene that
resulted in the amino acid substitution leu30 to pro (L30P). The L30P
substitution occurred in a conserved region that may represent a
dileucine motif, a sorting signal present in endosomal-lysosomal
targeting proteins thought to be important for intracellular
localization.

In transfection studies in HEK293 cells, Smith et al. (2012) observed
that co-overexpression of the L30P mutant with wildtype VIPAR (613401),
did not result in colocalization; rather, cytoplasmic distribution was
seen for both proteins.

.0004
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 1
VPS33B, IVS9DS, G-A, +1

See 608552.0002 and Taha et al. (2007).

.0005
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 1
VPS33B, IVS16DS, G-C, +5

In an unrelated boy and girl with relatively mild arthrogryposis, renal
dysfunction, and cholestasis-1 (208085), Smith et al. (2012) identified
compound heterozygosity for mutations in the VPS33B gene. In intron 16
of 1 allele, they both had a G-C transversion at the splice donor site
(c.1225+5G-C). On the other allele, the boy had deletion of exon 4
(c.240-577_290-156del; 608552.0006), causing a frameshift predicted to
result in a premature stop codon (Leu81SerfsTer5), whereas the girl had
a 2-bp deletion in exon 17 (1261_1262delCA; 608552.0007), causing a
frameshift predicted to result in premature termination
(Gln421ValfsTer8). Analysis of transcript from the splice site mutation
showed integration of 114 bp of intron 16 before termination with a
polyA tail. Thus the predicted protein includes 12 additional amino acid
residues before a stop codon, and exons 17 to 23 are absent from the
cDNA, resulting in a predicted protein length of 420 amino acids
compared to wildtype 617 amino acids. In transfection studies with
co-overexpression of the splice site mutation with wildtype VIPAR
(613401), specific fluorescent spots containing both proteins were
observed, although aggregates containing only VPS33B were also seen.
Smith et al. (2012) concluded that the c.1225+5G-C mutant retains
partial ability to interact with VIPAR. Cryo-immunogold electron
microscopy of HEK293 cells overexpressing the splice site mutation and
wildtype VIPAR showed the 2 proteins colocalizing mainly in
electron-dense cytoplasmic clusters that contained no membranes;
however, some staining for VPS33B could be detected on vesicles found at
the rims of these cytoplasmic aggregates. Smith et al. (2012) noted that
the VPS33B c.1225+5G-C mutation seemed to affect the ability of the
complexes to colocalize properly on tubular-vesicular recycling
membranes, which would likely abrogate at least partially their cellular
functioning.

.0006
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 1
VPS33B, EX4DEL

See 608552.0005 and Smith et al. (2012).

.0007
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 1
VPS33B, 2-BP DEL, 1261CA

See 608552.0005 and Smith et al. (2012).

*FIELD* RF
1. Carim, L.; Sumoy, L.; Andreu, N.; Estivill, X.; Escarceller, M.
: Cloning, mapping and expression analysis of VPS33B, the human orthologue
of rat Vps33b. Cytogenet. Cell Genet. 89: 92-95, 2000.

2. Cullinane, A. R.; Straatman-Iwanowska, A.; Zaucker, A.; Wakabayashi,
Y.; Bruce, C. K.; Luo, G.; Rahman, F.; Gurakan, F.; Utine, E.; Ozkan,
T. B.; Denecke, J.; Vukovic, J.; and 13 others: Mutations in VIPAR
cause an arthrogryposis, renal dysfunction and cholestasis syndrome
phenotype with defects in epithelial polarization. Nature Genet. 42:
303-312, 2010. Note: Erratum: Nature Genet. 43: 277 only, 2011.

3. Eastham, K. M.; McKiernan, P. J.; Milford, D. V.; Ramani, P.; Wyllie,
J.; van't Hoff, W.; Lynch, S. A.; Morris, A. A. M.: ARC syndrome:
an expanding range of phenotypes. Arch. Dis. Child. 85: 415-420,
2001.

4. Gissen, P.; Johnson, C. A.; Morgan, N. V.; Stapelbroek, J. M.;
Forshew, T.; Cooper, W. N.; McKiernan, P. J.; Klomp, L. W. J.; Morris,
A. A. M.; Wraith, J. E.; McClean, P.; Lynch, S. A.; and 12 others
: Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane
fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome. Nature
Genet. 36: 400-404, 2004.

5. Gissen, P.; Tee, L.; Johnson, C. A.; Genin, E.; Caliebe, A.; Chitayat,
D.; Clericuzio, C.; Denecke, J.; Di Rocco, M.; Fischler, B.; FitzPatrick,
D.; Garcia-Cazorla, A.; and 9 others: Clinical and molecular genetic
features of ARC syndrome. Hum. Genet. 120: 396-409, 2006.

6. Horslen, S. P.; Quarrell, O. W. J.; Tanner, M. S.: Liver histology
in the arthrogryposis multiplex congenita, renal dysfunction, and
cholestasis (ARC) syndrome: report of three new cases and review. J.
Med. Genet. 31: 62-64, 1994.

7. Huizing, M.; Didier, A.; Walenta, J.; Anikster, Y.; Gahl, W. A.;
Kramer, H.: Molecular cloning and characterization of human VPS18,
VPS11, VPS16, and VPS33. Gene 264: 241-247, 2001.

8. Smith, H.; Galmes, R.; Gogolina, E.; Straatman-Iwanowska, A.; Reay,
K.; Banushi, B.; Bruce, C. K.; Cullinane, A. R.; Romero, R.; Chang,
R.; Ackermann, O.; Baumann, C.; and 12 others: Associations among
genotype, clinical phenotype, and intracellular localization of trafficking
proteins in ARC syndrome. Hum. Mutat. 33: 1656-1664, 2012.

9. Taha, D.; Khider, A.; Cullinane, A. R.; Gissen, P.: A novel VPS33B
mutation in an ARC syndrome patient presenting with osteopenia and
fractures at birth. (Letter) Am. J. Med. Genet. 143A: 2835-2837,
2007.

*FIELD* CN
Marla J. F. O'Neill - updated: 5/13/2010
Marla J. F. O'Neill - updated: 4/24/2008
Marla J. F. O'Neill - updated: 2/15/2007
Victor A. McKusick - updated: 4/5/2004

*FIELD* CD
Patricia A. Hartz: 3/25/2004

*FIELD* ED
carol: 11/19/2013
mcolton: 11/15/2013
carol: 10/10/2012
terry: 5/14/2010
carol: 5/13/2010
wwang: 4/28/2008
terry: 4/24/2008
wwang: 2/15/2007
terry: 6/18/2004
alopez: 4/6/2004
terry: 4/5/2004
mgross: 3/25/2004

RBCC Red Blood Cell Collection

Full text data of VPS33B