Human Gene TMEM67 (ENST00000409623.7) Description and Page Index
Description: Homo sapiens transmembrane protein 67 (TMEM67), transcript variant 2, mRNA. (from RefSeq NM_001142301) RefSeq Summary (NM_001142301): The protein encoded by this gene localizes to the primary cilium and to the plasma membrane. The gene functions in centriole migration to the apical membrane and formation of the primary cilium. Multiple transcript variants encoding different isoforms have been found for this gene. Defects in this gene are a cause of Meckel syndrome type 3 (MKS3) and Joubert syndrome type 6 (JBTS6). [provided by RefSeq, Nov 2008]. Gencode Transcript: ENST00000409623.7 Gencode Gene: ENSG00000164953.15 Transcript (Including UTRs) Position: hg38 chr8:93,754,887-93,816,760 Size: 61,874 Total Exon Count: 29 Strand: + Coding Region Position: hg38 chr8:93,758,548-93,816,452 Size: 57,905 Coding Exon Count: 27
ID:MKS3_HUMAN DESCRIPTION: RecName: Full=Meckelin; AltName: Full=Meckel syndrome type 3 protein; AltName: Full=Transmembrane protein 67; 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. Required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication. Required for cell branching morphology. Essential for endoplasmic reticulum-associated degradation (ERAD) of surfactant protein C (SFTPC). SUBUNIT: Part of the tectonic-like complex (also named B9 complex) (By similarity). Interacts with DNAJB9, DNAJC10 and mutated SFTPC. Interacts with SYNE2 during the early establishment of cell polarity. Interacts (via C-terminus) with FLNA. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein. Cytoplasm, cytoskeleton, cilium basal body. Note=Localizes at the transition zone, a region between the basal body and the ciliary axoneme (By similarity). TISSUE SPECIFICITY: Widely expressed in adult and fetal tissues. Expressed at higher level in spinal cord. DISEASE: Note=Ciliary dysfunction leads 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. DISEASE: Defects in TMEM67 are the cause of Meckel syndrome type 3 (MKS3) [MIM:607361]. MKS3 is an autosomal recessive 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. DISEASE: Defects in TMEM67 are the cause of Joubert syndrome type 6 (JBTS6) [MIM:610688]. JBTS is an autosomal recessive 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. DISEASE: Defects in TMEM67 may be a cause of Bardet-Biedl syndrome (BBS) [MIM:209900]. A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. 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. Note=Genetic variations in TMEM67 may act as a modifier of the expression of Bardet-Biedl syndrome in patients who have 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 type 14. DISEASE: Defects in TMEM67 are a cause of COACH syndrome (COACHS) [MIM:216360]. It is a disorder characterized by mental retardation, ataxia due to cerebellar hypoplasia, 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. DISEASE: Defects in TMEM67 are the cause of nephronophthisis type 11 (NPHP11) [MIM:613550]. NPHP11 is 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. SEQUENCE CAUTION: Sequence=AAH32835.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAG52959.1; Type=Erroneous initiation; Note=Translation N-terminally extended; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TMEM67";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF09773 - Meckelin (Transmembrane protein 67)
ModBase Predicted Comparative 3D Structure on Q5HYA8
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.