RBCC

Full text data of MARVELD2

MARVELD2 (TRIC) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
MARVEL domain-containing protein 2 (Tricellulin)

UniProt Q8N4S9
ID MALD2_HUMAN Reviewed; 558 AA.
AC Q8N4S9; A1BQX0; A1BQX1; A8KA97; Q96NM9;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-JAN-2011, sequence version 2.
DT 22-JAN-2014, entry version 97.
DE RecName: Full=MARVEL domain-containing protein 2;
DE AltName: Full=Tricellulin;
GN Name=MARVELD2; Synonyms=TRIC;
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] (ISOFORMS 1 AND 2), AND VARIANT ILE-33.
RX PubMed=16365161; DOI=10.1083/jcb.200510043;
RA Ikenouchi J., Furuse M., Furuse K., Sasaki H., Tsukita S., Tsukita S.;
RT "Tricellulin constitutes a novel barrier at tricellular contacts of
RT epithelial cells.";
RL J. Cell Biol. 171:939-945(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), INVOLVEMENT IN DFNB49,
RP FUNCTION, AND VARIANT ILE-33.
RC TISSUE=Lung;
RX PubMed=17186462; DOI=10.1086/510022;
RA Riazuddin S., Ahmed Z.M., Fanning A.S., Lagziel A., Kitajiri S.,
RA Ramzan K., Khan S.N., Chattaraj P., Friedman P.L., Anderson J.M.,
RA Belyantseva I.A., Forge A., Riazuddin S., Friedman T.B.;
RT "Tricellulin is a tight-junction protein necessary for hearing.";
RL Am. J. Hum. Genet. 79:1040-1051(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ILE-33.
RC TISSUE=Brain, and Trachea;
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], AND VARIANT ILE-33.
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP ILE-33.
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116 AND SER-120, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116 AND SER-120, AND
RP MASS 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).
CC -!- FUNCTION: Plays a role in the formation of the epithelial
CC barriers. The separation of the endolymphatic and perilymphatic
CC spaces of the organ of Corti from one another by epithelial
CC barriers is required for normal hearing.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC Cell junction, tight junction (By similarity). Note=Found at
CC tricellular contacts (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=A, TRIC;
CC IsoId=Q8N4S9-1; Sequence=Displayed;
CC Name=2; Synonyms=TRICbeta;
CC IsoId=Q8N4S9-2; Sequence=VSP_022320, VSP_022321;
CC Name=3; Synonyms=A1;
CC IsoId=Q8N4S9-3; Sequence=VSP_035760;
CC -!- DISEASE: Deafness, autosomal recessive, 49 (DFNB49) [MIM:610153]:
CC A form of non-syndromic sensorineural hearing loss. Sensorineural
CC deafness results from damage to the neural receptors of the inner
CC ear, the nerve pathways to the brain, or the area of the brain
CC that receives sound information. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 1 MARVEL domain.
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DR EMBL; AB219936; BAE54513.1; -; mRNA.
DR EMBL; AB219937; BAE54514.1; -; mRNA.
DR EMBL; DQ682656; ABG89104.1; -; mRNA.
DR EMBL; DQ682657; ABG89105.1; -; mRNA.
DR EMBL; AK055094; BAB70853.1; -; mRNA.
DR EMBL; AK292962; BAF85651.1; -; mRNA.
DR EMBL; AC145146; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471137; EAW51277.1; -; Genomic_DNA.
DR EMBL; BC033689; AAH33689.1; -; mRNA.
DR RefSeq; NP_001033692.2; NM_001038603.2.
DR RefSeq; NP_001231663.1; NM_001244734.1.
DR RefSeq; XP_005248502.1; XM_005248445.1.
DR RefSeq; XP_005248503.1; XM_005248446.1.
DR RefSeq; XP_005248504.1; XM_005248447.1.
DR RefSeq; XP_005276814.1; XM_005276757.1.
DR RefSeq; XP_005276815.1; XM_005276758.1.
DR RefSeq; XP_005276816.1; XM_005276759.1.
DR RefSeq; XP_005276817.1; XM_005276760.1.
DR UniGene; Hs.657687; -.
DR ProteinModelPortal; Q8N4S9; -.
DR SMR; Q8N4S9; 441-548.
DR IntAct; Q8N4S9; 1.
DR STRING; 9606.ENSP00000323264; -.
DR PhosphoSite; Q8N4S9; -.
DR DMDM; 74728895; -.
DR PaxDb; Q8N4S9; -.
DR PRIDE; Q8N4S9; -.
DR Ensembl; ENST00000325631; ENSP00000323264; ENSG00000152939.
DR Ensembl; ENST00000454295; ENSP00000396244; ENSG00000152939.
DR Ensembl; ENST00000573599; ENSP00000460291; ENSG00000263043.
DR Ensembl; ENST00000576933; ENSP00000461265; ENSG00000263043.
DR GeneID; 153562; -.
DR KEGG; hsa:153562; -.
DR UCSC; uc003jwq.3; human.
DR CTD; 153562; -.
DR GeneCards; GC05P068746; -.
DR H-InvDB; HIX0004923; -.
DR HGNC; HGNC:26401; MARVELD2.
DR HPA; HPA018119; -.
DR MIM; 610153; phenotype.
DR MIM; 610572; gene.
DR neXtProt; NX_Q8N4S9; -.
DR Orphanet; 90636; Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
DR PharmGKB; PA134954584; -.
DR eggNOG; NOG264085; -.
DR HOGENOM; HOG000155323; -.
DR HOVERGEN; HBG079727; -.
DR InParanoid; Q8N4S9; -.
DR KO; K17291; -.
DR OMA; IHKDNEW; -.
DR PhylomeDB; Q8N4S9; -.
DR ChiTaRS; MARVELD2; human.
DR GeneWiki; MARVELD2; -.
DR GenomeRNAi; 153562; -.
DR NextBio; 87132; -.
DR PRO; PR:Q8N4S9; -.
DR ArrayExpress; Q8N4S9; -.
DR Bgee; Q8N4S9; -.
DR CleanEx; HS_MARVELD2; -.
DR Genevestigator; Q8N4S9; -.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0033010; C:paranodal junction; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IEA:Ensembl.
DR GO; GO:0005923; C:tight junction; IDA:MGI.
DR GO; GO:0045216; P:cell-cell junction organization; IMP:MGI.
DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR InterPro; IPR008253; Marvel.
DR InterPro; IPR010844; Occludin_RNApol2_elong_fac_ELL.
DR Pfam; PF01284; MARVEL; 1.
DR Pfam; PF07303; Occludin_ELL; 1.
DR PROSITE; PS51225; MARVEL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Coiled coil;
KW Complete proteome; Deafness; Hearing; Membrane;
KW Non-syndromic deafness; Phosphoprotein; Polymorphism;
KW Reference proteome; Tight junction; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 558 MARVEL domain-containing protein 2.
FT /FTId=PRO_0000271526.
FT TOPO_DOM 1 194 Cytoplasmic (Potential).
FT TRANSMEM 195 215 Helical; (Potential).
FT TOPO_DOM 216 223 Extracellular (Potential).
FT TRANSMEM 224 244 Helical; (Potential).
FT TOPO_DOM 245 254 Cytoplasmic (Potential).
FT TRANSMEM 255 275 Helical; (Potential).
FT TOPO_DOM 276 291 Extracellular (Potential).
FT TRANSMEM 292 312 Helical; (Potential).
FT TOPO_DOM 313 319 Cytoplasmic (Potential).
FT TRANSMEM 320 337 Helical; (Potential).
FT TOPO_DOM 338 341 Extracellular (Potential).
FT TRANSMEM 342 362 Helical; (Potential).
FT TOPO_DOM 363 558 Cytoplasmic (Potential).
FT DOMAIN 188 367 MARVEL.
FT COILED 466 490 Potential.
FT COILED 524 548 Potential.
FT COMPBIAS 45 52 Poly-Pro.
FT COMPBIAS 514 517 Poly-Lys.
FT MOD_RES 116 116 Phosphoserine.
FT MOD_RES 120 120 Phosphoserine.
FT VAR_SEQ 383 394 Missing (in isoform 3).
FT /FTId=VSP_035760.
FT VAR_SEQ 431 457 GHIPKPIVMPDYVAKYPVIQTDDERER -> RPANFFVFLV
FT EMGFHRVSQDDLDLLTS (in isoform 2).
FT /FTId=VSP_022320.
FT VAR_SEQ 458 558 Missing (in isoform 2).
FT /FTId=VSP_022321.
FT VARIANT 33 33 T -> I (in dbSNP:rs1185246).
FT /FTId=VAR_047436.
FT CONFLICT 356 356 L -> P (in Ref. 3; BAF85651).
FT CONFLICT 435 435 K -> R (in Ref. 3; BAF85651).
SQ SEQUENCE 558 AA; 64168 MW; 04F3FCB2CFDB162B CRC64;
MSNDGRSRNR DRRYDEVPSD LPYQDTTIRT HPTLHDSERA VSADPLPPPP LPLQPPFGPD
FYSSDTEEPA IAPDLKPVRR FVPDSWKNFF RGKKKDPEWD KPVSDIRYIS DGVECSPPAS
PARPNHRSPL NSCKDPYGGS EGTFSSRKEA DAVFPRDPYG SLDRHTQTVR TYSEKVEEYN
LRYSYMKSWA GLLRILGVVE LLLGAGVFAC VTAYIHKDSE WYNLFGYSQP YGMGGVGGLG
SMYGGYYYTG PKTPFVLVVA GLAWITTIII LVLGMSMYYR TILLDSNWWP LTEFGINVAL
FILYMAAAIV YVNDTNRGGL CYYPLFNTPV NAVFCRVEGG QIAAMIFLFV TMIVYLISAL
VCLKLWRHEA ARRHREYMEQ QEINEPSLSS KRKMCEMATS GDRQRDSEVN FKELRTAKMK
PELLSGHIPP GHIPKPIVMP DYVAKYPVIQ TDDERERYKA VFQDQFSEYK ELSAEVQAVL
RKFDELDAVM SRLPHHSESR QEHERISRIH EEFKKKKNDP TFLEKKERCD YLKNKLSHIK
QRIQEYDKVM NWDVQGYS
//

MIM 610153
*RECORD*
*FIELD* NO
610153
*FIELD* TI
#610153 DEAFNESS, AUTOSOMAL RECESSIVE 49; DFNB49
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moreDFNB49 is caused by mutation in the gene encoding tricellulin (MARVELD2;
610572).

MAPPING

Ramzan et al. (2005) reported 2 large consanguineous Pakistani families
with autosomal recessive congenital profound sensorineural hearing loss
of all frequencies. Genomewide linkage analysis followed by fine mapping
of both families showed linkage to a candidate disease locus, termed
DFNB49, on chromosome 5q12.3-q14.1 (maximum 2-point lod scores of 4.44
and 5.94 at D5S2055 and D5S424 in the 2 families, respectively).
Haplotype analysis delineated an 11-cM interval flanked by D5S647 and
D5S1501. Direct sequencing excluded mutations in coding regions of the
SLC30A5 (607819) and SLC12A2 (600840) genes.

Riazuddin et al. (2006) identified 6 additional DFNB49 families and
refined the critical interval to 2.4 Mb. They found homozygous mutations
in the MARVELD2 gene to be the cause of the disorder in all families.
Four families were homozygous for the same disease haplotype and carried
the same mutation located in the splice donor site of exon 4
(610572.0003). Two families segregated a deletion of this same splice
donor site (610572.0002), and 1 family segregated a mutation in the
splice acceptor site of exon 4 (610572.0001). Affected members of the
remaining family carried a nonsense mutation in exon 5 (610572.0004).
All of these mutations resulted in proteins that lacked the ability to
bind to the scaffolding protein ZO1 (601009) because of the loss of the
conserved C-terminal occludin-ELL domain.

In affected members of 3 consanguineous Pakistani kindreds with
autosomal recessive nonsyndromic deafness, Chishti et al. (2008)
identified 2 different homozygous mutations in the MARVELD2 gene
(612572.0003, 610572.0005), one of which had previously been reported.
The authors estimated that the prevalence of autosomal recessive
deafness due to MARVELD2 mutations in Pakistani families is 1.06%.

*FIELD* RF
1. Chishti, M. S.; Bhatti, A.; Tamim, S.; Lee, K.; McDonald, M.-L.;
Leal, S. M.; Ahmad, W.: Splice-site mutations in the TRIC gene underlie
autosomal recessive nonsyndromic hearing impairment in Pakistani families. J.
Hum. Genet. 53: 101-105, 2008.

2. Ramzan, K.; Shaikh, R. S.; Ahmad, J.; Khan, S. N.; Riazuddin, S.;
Ahmed, Z. M.; Friedman, T. B.; Wilcox, E. R.; Riazuddin, S.: A new
locus for nonsyndromic deafness DFNB49 maps to chromosome 5q12.3-q14.1. Hum.
Genet. 116: 17-22, 2005.

3. Riazuddin, S.; Ahmed, Z. M.; Fanning, A. S.; Lagziel, A.; Kitajiri,
S.; Ramzan, K.; Khan, S. N.; Chattaraj, P.; Friedman, P. L.; Anderson,
J. M.; Belyantseva, I. A.; Forge, A.; Riazuddin, S.; Friedman, T.
B.: Tricellulin is a tight-junction protein necessary for hearing. Am.
J. Hum. Genet. 79: 1040-1051, 2006.

*FIELD* CS
INHERITANCE:
Autosomal recessive

HEAD AND NECK:
[Ears];
Deafness, prelingual, profound (affects all frequencies)

MOLECULAR BASIS:
Caused by mutations in the marvel domain-containing protein 2 gene
(MARVELD2, 610572.0001)

*FIELD* CN
Cassandra L. Kniffin - updated: 07/07/2008

*FIELD* CD
Cassandra L. Kniffin: 6/1/2006

*FIELD* ED
ckniffin: 07/07/2008
joanna: 10/26/2006
ckniffin: 6/1/2006

*FIELD* CN
Cassandra L. Kniffin - updated: 7/7/2008
Victor A. McKusick - updated: 11/28/2006

*FIELD* CD
Cassandra L. Kniffin: 6/1/2006

*FIELD* ED
carol: 11/13/2008
ckniffin: 7/7/2008
alopez: 11/29/2006
terry: 11/28/2006
wwang: 9/20/2006
wwang: 6/5/2006
ckniffin: 6/1/2006

MIM 610572
*RECORD*
*FIELD* NO
610572
*FIELD* TI
*610572 MARVEL DOMAIN-CONTAINING PROTEIN 2; MARVELD2
;;MARVD2;;
TRICELLULIN; TRIC
*FIELD* TX
read more
DESCRIPTION

Tight junctions (TJ) prevent leakage of solutes through the paracellular
pathway of epithelial cells. MARVELD2, or tricellulin (TRIC), is an
integral membrane protein concentrated at the vertically oriented TJ
strands of tricellular contacts (Ikenouchi et al., 2005).

CLONING

Ikenouchi et al. (2005) cloned mouse Tric. The 555-amino acid protein
contains cytoplasmic N and C termini, 2 transmembrane domains, and 2
extracellular loops. Northern blot analysis detected high expression of
Tric in epithelium-derived tissues, including small intestine, kidney,
and lung. Western blot analysis of mouse epithelial cell lines revealed
an approximately 66-kD protein, as well as larger phosphorylated
intracellular forms. Immunofluorescence microscopy showed expression of
Tric predominantly at tricellular contacts where occludin (OCLN;
602876)-positive bicellular TJs converged. Tric-positive structures
appeared as short rods through confocal microscopy.

GENE FUNCTION

Ikenouchi et al. (2005) found that suppression of mouse Tric through RNA
interference resulted in a compromised epithelial barrier and
disorganized tricellular contacts and bicellular TJs. They concluded
that TRIC is critical for formation of the epithelial barrier.

In mouse, Riazuddin et al. (2006) demonstrated that in the inner ear,
tricellulin is concentrated at the tricellular tight junctions in
cochlear and vestibular epithelia, including the structurally complex
and extensive junctions between supporting and hair cells.

MAPPING

Ikenouchi et al. (2005) stated that the TRIC gene maps to chromosome 5
in tandem with the OCLN gene. The mouse genes map to chromosome 13.

MOLECULAR GENETICS

The inner ear has fluid-filled compartments of different ionic
compositions, including the endolymphatic and perilymphatic spaces of
the organ of Corti. The separation from one another by epithelial
barriers is required for normal hearing. Tricellulin is a tight junction
protein that contributes to the structure and function of tricellular
contacts of neighboring cells in many epithelial tissues. Riazuddin et
al. (2006) demonstrated 4 different homozygous mutations of TRIC causing
nonsyndromic deafness (DFNB49; 610153), a surprisingly limited phenotype
given the widespread tissue distribution of tricellulin in epithelial
cells. They demonstrated that there are multiple alternatively spliced
isoforms in TRIC in various tissues and that mutations of TRIC
associated with hearing loss remove all or most of the conserved
C-terminal occludin-ELL domain, which binds to the cytosolic scaffolding
protein ZO1 (601009). Production of a wildtype isoform of tricellulin
that lacks this conserved region was unaffected by the mutant alleles;
Riazuddin et al. (2006) hypothesized that this isoform is sufficient for
structural and functional integrity of the epithelial barriers outside
the inner ear, thus explaining the limited phenotype.

In affected members of 3 consanguineous Pakistani kindreds with
autosomal recessive nonsyndromic deafness, Chishti et al. (2008)
identified 2 different homozygous mutations in the MARVELD2 gene
(612572.0003, 610572.0005), one of which had previously been reported.
The authors estimated that the prevalence of autosomal recessive
deafness due to MARVELD2 mutations in Pakistani families is 1.06%.

*FIELD* AV
.0001
DEAFNESS, AUTOSOMAL RECESSIVE 49
MARVELD2, IVS3AS, G-A, -1

In a family with deafness defined as DFNB49 (610153) on the basis of
mapping to 5q12.3-q14.1, Riazuddin et al. (2006) described a homozygous
splice site mutation, IVS3-1G-A, in the MARVELD2 gene.

.0002
DEAFNESS, AUTOSOMAL RECESSIVE 49
MARVELD2, 4-BP DEL, IVS4+2TGAG

In 2 Pakistani families with DFNB49 (610153), Riazuddin et al. (2006)
found deletion of nucleotides TGAG at positions 2 through 5 in the donor
site of IVS4 of the MARVELD2 gene.

.0003
DEAFNESS, AUTOSOMAL RECESSIVE 49
MARVELD2, IVS4DS, T-C, +2

In 4 Pakistani families with DFNB49 (610153), Riazuddin et al. (2006)
demonstrated homozygosity for a donor splice site mutation, IVS4+2T-C,
in the MARVELD2 gene.

Chishti et al. (2008) identified the same splice site mutation in
affected members from 2 additional consanguineous Pakistani families
with autosomal recessive deafness.

.0004
DEAFNESS, NEUROSENSORY, AUTOSOMAL RECESSIVE 49
MARVELD2, ARG500TER

In a Pakistani family with DFNB49 (610153), Riazuddin et al. (2006)
found that autosomal recessive neurosensory deafness (DFNB49; 610153)
was related to a 1498C-T transition in exon 5 of the MARVELD2 gene that
resulted in an arg500-to-stop substitution (R500X).

.0005
DEAFNESS, AUTOSOMAL RECESSIVE 49
MARVELD2, IVS4DS, G-A, +1

In affected members of a consanguineous Pakistani family with DFNB49
(610153), Chishti et al. (2008) identified a homozygous G-to-A
transition in intron 4 of the MARVELD2 gene, resulting in a splice site
mutation.

*FIELD* RF
1. Chishti, M. S.; Bhatti, A.; Tamim, S.; Lee, K.; McDonald, M.-L.;
Leal, S. M.; Ahmad, W.: Splice-site mutations in the TRIC gene underlie
autosomal recessive nonsyndromic hearing impairment in Pakistani families. J.
Hum. Genet. 53: 101-105, 2008.

2. Ikenouchi, J.; Furuse, M.; Furuse, K.; Sasaki, H.; Tsukita, S.;
Tsukita, S.: Tricellulin constitutes a novel barrier at tricellular
contacts of epithelial cells. J. Cell Biol. 171: 939-945, 2005.

3. Riazuddin, S.; Ahmed, Z. M.; Fanning, A. S.; Lagziel, A.; Kitajiri,
S.; Ramzan, K.; Khan, S. N.; Chattaraj, P.; Friedman, P. L.; Anderson,
J. M.; Belyantseva, I. A.; Forge, A.; Riazuddin, S.; Friedman, T.
B.: Tricellulin is a tight-junction protein necessary for hearing. Am.
J. Hum. Genet. 79: 1040-1051, 2006.

*FIELD* CN
Cassandra L. Kniffin - updated: 7/7/2008
Victor A. McKusick - updated: 11/28/2006

*FIELD* CD
Paul J. Converse: 11/15/2006

*FIELD* ED
carol: 11/13/2008
ckniffin: 7/7/2008
alopez: 12/18/2006
alopez: 11/29/2006
terry: 11/28/2006
mgross: 11/15/2006

RBCC Red Blood Cell Collection

Full text data of MARVELD2