TM218_HUMAN
ID TM218_HUMAN Reviewed; 115 AA.
AC A2RU14; B7ZM48;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Transmembrane protein 218;
GN Name=TMEM218;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP VARIANTS JBTS39 VAL-9; CYS-80 AND HIS-80, VARIANT 59-ARG--TYR-115 DEL,
RP INVOLVEMENT IN JBTS39, AND INVOLVEMENT IN CILIOPATHIES.
RX PubMed=33791682; DOI=10.1016/j.xhgg.2020.100016;
RG University of Washington Center for Mendelian Genomics;
RA Van De Weghe J.C., Giordano J.L., Mathijssen I.B., Mojarrad M.,
RA Lugtenberg D., Miller C.V., Dempsey J.C., Mohajeri M.S.A., van Leeuwen E.,
RA Pajkrt E., Klaver C.C.W., Houlden H., Eslahi A., Waters A.M., Bamshad M.J.,
RA Nickerson D.A., Aggarwal V.S., de Vries B.B.A., Maroofian R., Doherty D.;
RT "TMEM218 dysfunction causes ciliopathies, including Joubert and Meckel
RT syndromes.";
RL HGG Adv. 2:0-0(2021).
RN [4]
RP VARIANT JBTS39 SER-37, VARIANT 59-ARG--TYR-115 DEL, INVOLVEMENT IN JBTS39,
RP INVOLVEMENT IN CILIOPATHIES, AND INTERACTION WITH TMEM67.
RX PubMed=35137054; DOI=10.1093/hmg/ddac027;
RA Epting D., Decker E., Ott E., Eisenberger T., Bader I., Bachmann N.,
RA Bergmann C.;
RT "The ciliary transition zone protein TMEM218 synergistically interacts with
RT the NPHP module and its reduced dosage leads to a wide range of syndromic
RT ciliopathies.";
RL Hum. Mol. Genet. 0:0-0(2022).
CC -!- FUNCTION: May be involved in ciliary biogenesis or function.
CC {ECO:0000250|UniProtKB:Q9CQ44}.
CC -!- SUBUNIT: Interacts with TMEM67. {ECO:0000269|PubMed:35137054}.
CC -!- INTERACTION:
CC A2RU14; Q96BI3: APH1A; NbExp=3; IntAct=EBI-10173151, EBI-2606935;
CC A2RU14; P41181: AQP2; NbExp=3; IntAct=EBI-10173151, EBI-12701138;
CC A2RU14; Q13520: AQP6; NbExp=3; IntAct=EBI-10173151, EBI-13059134;
CC A2RU14; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-10173151, EBI-11343438;
CC A2RU14; Q8WWH4: ASZ1; NbExp=3; IntAct=EBI-10173151, EBI-12239061;
CC A2RU14; O15342: ATP6V0E1; NbExp=3; IntAct=EBI-10173151, EBI-12935759;
CC A2RU14; J3KQ12: BSCL2; NbExp=3; IntAct=EBI-10173151, EBI-11532900;
CC A2RU14; Q9UGN4: CD300A; NbExp=3; IntAct=EBI-10173151, EBI-10320732;
CC A2RU14; P19397: CD53; NbExp=3; IntAct=EBI-10173151, EBI-6657396;
CC A2RU14; P11912: CD79A; NbExp=3; IntAct=EBI-10173151, EBI-7797864;
CC A2RU14; P57739: CLDN2; NbExp=3; IntAct=EBI-10173151, EBI-751440;
CC A2RU14; Q8IUN9: CLEC10A; NbExp=3; IntAct=EBI-10173151, EBI-2873246;
CC A2RU14; Q6ZS10: CLEC17A; NbExp=3; IntAct=EBI-10173151, EBI-11977093;
CC A2RU14; Q7Z7G2: CPLX4; NbExp=3; IntAct=EBI-10173151, EBI-18013275;
CC A2RU14; Q96BA8: CREB3L1; NbExp=7; IntAct=EBI-10173151, EBI-6942903;
CC A2RU14; P16410: CTLA4; NbExp=3; IntAct=EBI-10173151, EBI-1030991;
CC A2RU14; Q9Y4D2: DAGLA; NbExp=3; IntAct=EBI-10173151, EBI-12808806;
CC A2RU14; Q15125: EBP; NbExp=3; IntAct=EBI-10173151, EBI-3915253;
CC A2RU14; Q9NXB9: ELOVL2; NbExp=3; IntAct=EBI-10173151, EBI-17206972;
CC A2RU14; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-10173151, EBI-18535450;
CC A2RU14; P54849: EMP1; NbExp=3; IntAct=EBI-10173151, EBI-4319440;
CC A2RU14; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-10173151, EBI-781551;
CC A2RU14; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-10173151, EBI-18304435;
CC A2RU14; A2A2Y4: FRMD3; NbExp=3; IntAct=EBI-10173151, EBI-6911547;
CC A2RU14; Q8TB36: GDAP1; NbExp=3; IntAct=EBI-10173151, EBI-11110431;
CC A2RU14; P08034: GJB1; NbExp=3; IntAct=EBI-10173151, EBI-17565645;
CC A2RU14; Q9NTQ9: GJB4; NbExp=3; IntAct=EBI-10173151, EBI-12831526;
CC A2RU14; O95452: GJB6; NbExp=3; IntAct=EBI-10173151, EBI-13345609;
CC A2RU14; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-10173151, EBI-13345167;
CC A2RU14; Q9BZJ8: GPR61; NbExp=3; IntAct=EBI-10173151, EBI-12808020;
CC A2RU14; Q8TED1: GPX8; NbExp=3; IntAct=EBI-10173151, EBI-11721746;
CC A2RU14; P38484: IFNGR2; NbExp=3; IntAct=EBI-10173151, EBI-3905457;
CC A2RU14; P48051: KCNJ6; NbExp=3; IntAct=EBI-10173151, EBI-12017638;
CC A2RU14; O95279: KCNK5; NbExp=3; IntAct=EBI-10173151, EBI-3934936;
CC A2RU14; P43628: KIR2DL3; NbExp=3; IntAct=EBI-10173151, EBI-8632435;
CC A2RU14; Q5T700: LDLRAD1; NbExp=8; IntAct=EBI-10173151, EBI-10173166;
CC A2RU14; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-10173151, EBI-2820517;
CC A2RU14; Q8N112: LSMEM2; NbExp=5; IntAct=EBI-10173151, EBI-10264855;
CC A2RU14; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-10173151, EBI-11956541;
CC A2RU14; Q96HJ5: MS4A3; NbExp=5; IntAct=EBI-10173151, EBI-12806656;
CC A2RU14; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-10173151, EBI-3923617;
CC A2RU14; Q9Y5X5-3: NPFFR2; NbExp=3; IntAct=EBI-10173151, EBI-18076879;
CC A2RU14; P12004: PCNA; NbExp=4; IntAct=EBI-10173151, EBI-358311;
CC A2RU14; Q9BQ51: PDCD1LG2; NbExp=3; IntAct=EBI-10173151, EBI-16427978;
CC A2RU14; Q96FE7: PIK3IP1; NbExp=3; IntAct=EBI-10173151, EBI-10285708;
CC A2RU14; Q53GL0: PLEKHO1; NbExp=3; IntAct=EBI-10173151, EBI-949945;
CC A2RU14; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-10173151, EBI-10192441;
CC A2RU14; Q9NR31: SAR1A; NbExp=3; IntAct=EBI-10173151, EBI-3920694;
CC A2RU14; A0A0S2Z4U3: SDC3; NbExp=3; IntAct=EBI-10173151, EBI-10204280;
CC A2RU14; Q96EP9: SLC10A4; NbExp=3; IntAct=EBI-10173151, EBI-17456472;
CC A2RU14; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-10173151, EBI-18159983;
CC A2RU14; P54219-3: SLC18A1; NbExp=3; IntAct=EBI-10173151, EBI-17595455;
CC A2RU14; Q9BZL3: SMIM3; NbExp=3; IntAct=EBI-10173151, EBI-741850;
CC A2RU14; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-10173151, EBI-17280858;
CC A2RU14; Q96CE8: TM4SF18; NbExp=3; IntAct=EBI-10173151, EBI-13351685;
CC A2RU14; Q6PL24: TMED8; NbExp=3; IntAct=EBI-10173151, EBI-11603430;
CC A2RU14; Q9BVX2: TMEM106C; NbExp=3; IntAct=EBI-10173151, EBI-2821497;
CC A2RU14; Q6ZP80: TMEM182; NbExp=3; IntAct=EBI-10173151, EBI-10255122;
CC A2RU14; Q6UWW9: TMEM207; NbExp=3; IntAct=EBI-10173151, EBI-13301303;
CC A2RU14; Q8WY98: TMEM234; NbExp=3; IntAct=EBI-10173151, EBI-8642211;
CC A2RU14; Q96B21: TMEM45B; NbExp=3; IntAct=EBI-10173151, EBI-3923061;
CC A2RU14; Q4KMG9: TMEM52B; NbExp=3; IntAct=EBI-10173151, EBI-18178701;
CC A2RU14; Q6PEY1: TMEM88; NbExp=3; IntAct=EBI-10173151, EBI-17198826;
CC A2RU14; O15393-2: TMPRSS2; NbExp=3; IntAct=EBI-10173151, EBI-12345267;
CC A2RU14; P34981: TRHR; NbExp=3; IntAct=EBI-10173151, EBI-18055230;
CC A2RU14; O95859: TSPAN12; NbExp=3; IntAct=EBI-10173151, EBI-2466403;
CC A2RU14; Q8WUV1: TSPAN18; NbExp=3; IntAct=EBI-10173151, EBI-17670824;
CC A2RU14; Q9H7M9: VSIR; NbExp=3; IntAct=EBI-10173151, EBI-744988;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q9CQ44}. Note=Localizes at the transition zone,
CC a region between the basal body and the ciliary axoneme.
CC {ECO:0000250|UniProtKB:Q9CQ44}.
CC -!- DISEASE: Note=TMEM218 mutations result in ciliary dysfunction leading
CC to a broad spectrum of disorders, collectively termed ciliopathies.
CC Overlapping clinical features include retinal degeneration, renal
CC cystic disease, skeletal abnormalities, fibrosis of various organ, and
CC a complex range of anatomical and functional defects of the central and
CC peripheral nervous system. The ciliopathy range of diseases includes
CC Meckel-Gruber syndrome, Bardet-Biedl syndrome, Joubert syndrome, and
CC nephronophtisis among others. Single-locus allelism is insufficient to
CC explain the variable penetrance and expressivity of such disorders,
CC leading to the suggestion that variations across multiple sites of the
CC ciliary proteome influence the clinical outcome.
CC {ECO:0000269|PubMed:33791682, ECO:0000269|PubMed:35137054}.
CC -!- DISEASE: Joubert syndrome 39 (JBTS39) [MIM:619562]: A form of Joubert
CC syndrome, a disorder presenting with cerebellar ataxia, oculomotor
CC apraxia, hypotonia, neonatal breathing abnormalities and psychomotor
CC delay. Neuroradiologically, it is characterized by cerebellar vermian
CC hypoplasia/aplasia, thickened and reoriented superior cerebellar
CC peduncles, and an abnormally large interpeduncular fossa, giving the
CC appearance of a molar tooth on transaxial slices (molar tooth sign).
CC Additional variable features include retinal dystrophy, renal disease,
CC liver fibrosis, and polydactyly. JBTS39 inheritance is autosomal
CC recessive. {ECO:0000269|PubMed:33791682, ECO:0000269|PubMed:35137054}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the TMEM218 family. {ECO:0000305}.
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DR EMBL; CH471065; EAW67625.1; -; Genomic_DNA.
DR EMBL; BC132716; AAI32717.1; -; mRNA.
DR EMBL; BC132718; AAI32719.1; -; mRNA.
DR EMBL; BC144270; AAI44271.1; -; mRNA.
DR EMBL; BC144277; AAI44278.1; -; mRNA.
DR CCDS; CCDS31715.1; -.
DR RefSeq; NP_001074015.1; NM_001080546.2.
DR RefSeq; NP_001245167.1; NM_001258238.1.
DR RefSeq; NP_001245168.1; NM_001258239.1.
DR RefSeq; NP_001245169.1; NM_001258240.1.
DR RefSeq; NP_001245170.1; NM_001258241.1.
DR RefSeq; NP_001245171.1; NM_001258242.1.
DR RefSeq; NP_001245172.1; NM_001258243.1.
DR RefSeq; NP_001245173.1; NM_001258244.1.
DR RefSeq; NP_001245174.1; NM_001258245.1.
DR RefSeq; NP_001245175.1; NM_001258246.1.
DR RefSeq; NP_001245176.1; NM_001258247.1.
DR RefSeq; XP_006718846.1; XM_006718783.3.
DR RefSeq; XP_016872811.1; XM_017017322.1.
DR RefSeq; XP_016872812.1; XM_017017323.1.
DR RefSeq; XP_016872813.1; XM_017017324.1.
DR AlphaFoldDB; A2RU14; -.
DR SMR; A2RU14; -.
DR BioGRID; 128583; 76.
DR IntAct; A2RU14; 68.
DR STRING; 9606.ENSP00000436596; -.
DR BioMuta; TMEM218; -.
DR MassIVE; A2RU14; -.
DR PaxDb; A2RU14; -.
DR PeptideAtlas; A2RU14; -.
DR PRIDE; A2RU14; -.
DR ProteomicsDB; 491; -.
DR TopDownProteomics; A2RU14; -.
DR Antibodypedia; 50074; 8 antibodies from 7 providers.
DR DNASU; 219854; -.
DR Ensembl; ENST00000279968.8; ENSP00000279968.4; ENSG00000150433.10.
DR Ensembl; ENST00000526175.5; ENSP00000436177.1; ENSG00000150433.10.
DR Ensembl; ENST00000527271.5; ENSP00000436162.1; ENSG00000150433.10.
DR Ensembl; ENST00000527766.5; ENSP00000435526.1; ENSG00000150433.10.
DR Ensembl; ENST00000529583.5; ENSP00000433374.1; ENSG00000150433.10.
DR Ensembl; ENST00000531909.5; ENSP00000436596.1; ENSG00000150433.10.
DR Ensembl; ENST00000532407.5; ENSP00000434597.1; ENSG00000150433.10.
DR Ensembl; ENST00000682305.1; ENSP00000506979.1; ENSG00000150433.10.
DR GeneID; 219854; -.
DR KEGG; hsa:219854; -.
DR MANE-Select; ENST00000682305.1; ENSP00000506979.1; NM_001258244.2; NP_001245173.1.
DR UCSC; uc010sax.5; human.
DR CTD; 219854; -.
DR DisGeNET; 219854; -.
DR GeneCards; TMEM218; -.
DR HGNC; HGNC:27344; TMEM218.
DR HPA; ENSG00000150433; Low tissue specificity.
DR MalaCards; TMEM218; -.
DR MIM; 619285; gene.
DR MIM; 619562; phenotype.
DR neXtProt; NX_A2RU14; -.
DR OpenTargets; ENSG00000150433; -.
DR PharmGKB; PA162406569; -.
DR VEuPathDB; HostDB:ENSG00000150433; -.
DR eggNOG; ENOG502S2I1; Eukaryota.
DR GeneTree; ENSGT00390000016247; -.
DR InParanoid; A2RU14; -.
DR OMA; PATEMKI; -.
DR OrthoDB; 1590037at2759; -.
DR PhylomeDB; A2RU14; -.
DR TreeFam; TF328597; -.
DR PathwayCommons; A2RU14; -.
DR SignaLink; A2RU14; -.
DR BioGRID-ORCS; 219854; 7 hits in 1067 CRISPR screens.
DR ChiTaRS; TMEM218; human.
DR GenomeRNAi; 219854; -.
DR Pharos; A2RU14; Tdark.
DR PRO; PR:A2RU14; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; A2RU14; protein.
DR Bgee; ENSG00000150433; Expressed in right uterine tube and 178 other tissues.
DR ExpressionAtlas; A2RU14; baseline and differential.
DR Genevisible; A2RU14; HS.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR InterPro; IPR026771; Tmem218.
DR PANTHER; PTHR31622; PTHR31622; 1.
PE 1: Evidence at protein level;
KW Cell projection; Ciliopathy; Disease variant; Joubert syndrome; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..115
FT /note="Transmembrane protein 218"
FT /id="PRO_0000321836"
FT TRANSMEM 5..25
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..101
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VARIANT 9
FT /note="G -> V (in JBTS39; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33791682"
FT /id="VAR_086385"
FT VARIANT 37
FT /note="R -> S (in JBTS39; fails to rescue the ciliopathy
FT phenotype in a zebrafish disease model)"
FT /evidence="ECO:0000269|PubMed:35137054"
FT /id="VAR_086402"
FT VARIANT 59..115
FT /note="Missing (probable disease-associated variant found
FT in patients with Meckel syndrome)"
FT /evidence="ECO:0000269|PubMed:33791682,
FT ECO:0000269|PubMed:35137054"
FT /id="VAR_086386"
FT VARIANT 80
FT /note="R -> C (in JBTS39)"
FT /evidence="ECO:0000269|PubMed:33791682"
FT /id="VAR_086387"
FT VARIANT 80
FT /note="R -> H (in JBTS39)"
FT /evidence="ECO:0000269|PubMed:33791682"
FT /id="VAR_086388"
SQ SEQUENCE 115 AA; 12459 MW; 82641C83F92E2337 CRC64;
MAGTVLGVGA GVFILALLWV AVLLLCVLLS RASGAARFSV IFLFFGAVII TSVLLLFPRA
GEFPAPEVEV KIVDDFFIGR YVLLAFLSAI FLGGLFLVLI HYVLEPIYAK PLHSY
