TMEM67
entrez
91147
canonical
uniprot
Q5HYA8
canonical
ensembl
ENSG00000164953
resolver
ensp
ENSP00000314488
resolver
ensp
ENSP00000389998
resolver
ensp
ENSP00000403035
resolver
ensp
ENSP00000506985
resolver
ensp
ENSP00000508192
resolver
enst
ENST00000323130
resolver
enst
ENST00000453321
resolver
enst
ENST00000453906
resolver
genesymbol
TMEM67
resolver
genesymbol_syn
MKS3
resolver
hgnc
HGNC:28396
resolver
uniprot
B3KRU5
resolver
uniprot
B3KT47
resolver
uniprot
C9JHI2
resolver
uniprot
G5E9H2
resolver
uniprot
Q3ZCX3
resolver
uniprot
Q7Z5T8
resolver
uniprot
Q8IZ06
resolver
uniprot_entry
C9JHI2_HUMAN
resolver
uniprot_entry
MKS3_HUMAN
resolver
uniprot_sec
B3KRU5
resolver
uniprot_sec
B3KT47
resolver
uniprot_sec
G5E9H2
resolver
uniprot_sec
Q3ZCX3
resolver
uniprot_sec
Q7Z5T8
resolver
uniprot_sec
Q8IZ06
resolver
amino_acid_sequence
MATRGGAGVAMAVWSLLSARAVTAFLLLFLPRFLQAQTFSFPFQQPEKCDNNQYFDISALSCVPCGANQRQDARGTSCVCLPGFQMISNNGGPAIICKKCPENMKGVTEDGWNCISCPSDLTAEGKCHCPIGHILVERDINGTLLSQATCELCDGNENSFMVVNALGDRCVRCEPTFVNTSRSCACSEPNILTGGLCFSSTGNFPLRRISAARYGEVGMSLTSEWFAKYLQSSAAACWVYANLTSCQALGNMCVMNMNSYDFATFDACGLFQFIFENTAGLSTVHSISFWRQNLPWLFYGDQLGLAPQVLSSTSLPTNFSFKGENQNTKLKFVAASYDIRGNFLKWQTLEGGVLQLCPDTETRLNAAYSFGTTYQQNCEIPISKILIDFPTPIFYDVYLEYTDENQHQYILAVPVLNLNLQHNKIFVNQDSNSGKWLLTRRIFLVDAVSGRENDLGTQPRVIRVATQISLSVHLVPNTINGNIYPPLITIAYSDIDIKDANSQSVKVSFSVTYEMDHGEAHVQTDIALGVLGGLAVLASLLKTAGWKRRIGSPMIDLQTVVKFLVYYAGDLANVFFIITVGTGLYWLIFFKAQKSVSVLLPMPIQEERFVTYVGCAFALKALQFLHKLISQITIDVFFIDWERPKGKVLKAVEGEGGVRSATVPVSIWRTYFVANEWNEIQTVRKINSLFQVLTVLFFLEVVGFKNLALMDSSSSLSRNPPSYIAPYSCILRYAVSAALWLAIGIIQVVFFAVFYERFIEDKIRQFVDLCSMSNISVFLLSHKCFGYYIHGRSVHGHADTNMEEMNMNLKREAENLCSQRGLVPNTDGQTFEIAISNQMRQHYDRIHETLIRKNGPARLLSSSASTFEQSIKAYHMMNKFLGSFIDHVHKEMDYFIKDKLLLERILGMEFMEPMEKSIFYNDEGYSFSSVLYYGNEATLLIFDLLFFCVVDLACQNFILASFLTYLQQEIFRYIRNTVGQKNLASKTLVDQRFLI
uniprot
proteins
disease_involvement
DISEASE: Note=TMEM67 mutations result in ciliary dysfunction leading to a broad spectrum of disorders, collectively termed ciliopathies. Overlapping clinical features include retinal degeneration, renal cystic disease, skeletal abnormalities, fibrosis of various organ, and a complex range of anatomical and functional defects of the central and peripheral nervous system. The ciliopathy range of diseases includes Meckel-Gruber syndrome, Bardet-Biedl syndrome, Joubert syndrome, and nephronophtisis among others. Single-locus allelism is insufficient to explain the variable penetrance and expressivity of such disorders, leading to the suggestion that variations across multiple sites of the ciliary proteome influence the clinical outcome. {ECO:0000269|PubMed:18327255, ECO:0000269|PubMed:21633164}.; DISEASE: Meckel syndrome 3 (MKS3) [MIM:607361]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:16415887, ECO:0000269|PubMed:17185389, ECO:0000269|PubMed:17377820, ECO:0000269|PubMed:19466712, ECO:0000269|PubMed:20232449, ECO:0000269|PubMed:26035863, ECO:0000269|PubMed:26191240, ECO:0000269|PubMed:31411728, ECO:0000269|PubMed:34964473}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Joubert syndrome 6 (JBTS6) [MIM:610688]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. {ECO:0000269|PubMed:17160906, ECO:0000269|PubMed:19508969, ECO:0000269|PubMed:19574260, ECO:0000269|PubMed:21633164, ECO:0000269|PubMed:26477546, ECO:0000269|PubMed:32000717}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Bardet-Biedl syndrome 14 (BBS14) [MIM:615991]: A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and intellectual disability. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. {ECO:0000269|PubMed:18327255}. Note=The gene represented in this entry may act as a disease modifier. TMEM67 variations may influence the expression of Bardet-Biedl syndrome in patients who have causative mutations in other genes. Heterozygosity for a complex mutation in the TMEM67 gene coding for a protein with 2 in cis changes, and homozygosity for a truncating mutation of the CEP290 gene has been found in a patient with Bardet-Biedl syndrome 14.; DISEASE: COACH syndrome 1 (COACH1) [MIM:216360]: A form of COACH syndrome, a disorder characterized by cerebellar vermis hypoplasia, developmental delay, impaired intellectual development, ataxia, and hepatic fibrosis. Patients present the molar tooth sign, a midbrain-hindbrain malformation pathognomonic for Joubert syndrome and related disorders. Other features, such as coloboma and renal cysts, may be variable. COACH1 inheritance is autosomal recessive. {ECO:0000269|PubMed:19058225, ECO:0000269|PubMed:19574260, ECO:0000269|PubMed:28860541, ECO:0000269|PubMed:34964473}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Nephronophthisis 11 (NPHP11) [MIM:613550]: A disorder characterized by the association of nephronophthisis with hepatic fibrosis. Nephronophthisis is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. Typical clinical features are chronic renal failure, anemia, polyuria, polydipsia, isosthenuria, and growth retardation. Associations with extrarenal symptoms, especially ocular lesions, are frequent. {ECO:0000269|PubMed:19508969}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: RHYNS syndrome (RHYNS) [MIM:602152]: An autosomal recessive syndrome characterized by gaze palsy, retinitis pigmentosa, sensorineural hearing loss, hypopituitarism, nephronophthisis, and skeletal dysplasia. {ECO:0000269|PubMed:29891882}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Required for ciliary structure and function. Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition (By similarity). Involved in centrosome migration to the apical cell surface during early ciliogenesis. Involved in the regulation of cilia length and appropriate number through the control of centrosome duplication. Is a key regulator of stereociliary bundle orientation (By similarity). Required for epithelial cell branching morphology. Essential for endoplasmic reticulum-associated degradation (ERAD) of surfactant protein C (SFTPC). Involved in the negative regulation of canonical Wnt signaling, and activation of the non-canonical cascade stimulated by WNT5A (PubMed:26035863). In non-canonical Wnt signaling, it may act as ROR2 coreceptor (By similarity). {ECO:0000250|UniProtKB:Q8BR76, ECO:0000269|PubMed:17185389, ECO:0000269|PubMed:19515853, ECO:0000269|PubMed:19596800, ECO:0000269|PubMed:19815549, ECO:0000269|PubMed:26035863}.
uniprot
proteins
mass_dalton
111745
uniprot
proteins
mutagenesis
MUTAGEN 170; /note="C->Y: Decreased function in non-canonical Wnt signaling activation. When expressed in TMEM67-null cells does not induce ROR2 phosphorylation upon stimulation by WNT5A."; /evidence="ECO:0000269|PubMed:34964473"; MUTAGEN 176; /note="T->I: Does not affect function in non-canonical Wnt signaling activation. When expressed in TMEM67-null cells it induces ROR2 phosphorylation upon stimulation by WNT5A."; /evidence="ECO:0000269|PubMed:34964473"; MUTAGEN 790; /note="H->R: Decreased function in non-canonical Wnt signaling activation. When expressed in TMEM67-null cells does not induce ROR2 phosphorylation upon stimulation by WNT5A."; /evidence="ECO:0000269|PubMed:34964473"; MUTAGEN 979; /note="G->R: Does not affect function in non-canonical Wnt signaling activation. When expressed in TMEM67-null cells it induces ROR2 phosphorylation upon stimulation by WNT5A."; /evidence="ECO:0000269|PubMed:34964473
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16415887
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
17160906
uniprot
proteins
pubmed
17185389
uniprot
proteins
pubmed
17377820
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18327255
uniprot
proteins
pubmed
19058225
uniprot
proteins
pubmed
19466712
uniprot
proteins
pubmed
19508969
uniprot
proteins
pubmed
19515853
uniprot
proteins
pubmed
19574260
uniprot
proteins
pubmed
19596800
uniprot
proteins
pubmed
19815549
uniprot
proteins
pubmed
20232449
uniprot
proteins
pubmed
21633164
uniprot
proteins
pubmed
22121117
uniprot
proteins
pubmed
26035863
uniprot
proteins
pubmed
26191240
uniprot
proteins
pubmed
26477546
uniprot
proteins
pubmed
28860541
uniprot
proteins
pubmed
29891882
uniprot
proteins
pubmed
31411728
uniprot
proteins
pubmed
32000717
uniprot
proteins
pubmed
34731008
uniprot
proteins
pubmed
34964473
uniprot
proteins
pubmed
35137054
uniprot
proteins
sequence_length
995
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17185389}; Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:19815549}; Multi-pass membrane protein {ECO:0000255}. Cell projection, cilium {ECO:0000269|PubMed:17185389}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000269|PubMed:22121117}. Note=Localizes at the transition zone, a region between the basal body and the ciliary axoneme (PubMed:22121117). {ECO:0000269|PubMed:22121117}.
uniprot
proteins
transmembrane_region
TRANSMEM 520..548; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:34731008"; TRANSMEM 559..590; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:34731008"; TRANSMEM 604..631; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:34731008"; TRANSMEM 671..701; /note="Discontinuously helical; Name=4"; /evidence="ECO:0000269|PubMed:34731008"; TRANSMEM 732..771; /note="Discontinuously helical; Name=5"; /evidence="ECO:0000269|PubMed:34731008"; TRANSMEM 927..952; /note="Discontinuously helical; Name=6"; /evidence="ECO:0000269|PubMed:34731008"; TRANSMEM 958..985; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:34731008
uniprot
proteins