TMEM231
transmembrane protein 231, the group of MKS complex
Basic information
Region (hg38): 16:75536740-75556289
Links
Phenotypes
GenCC
Source:
- Meckel syndrome (Supportive), mode of inheritance: AR
- Joubert syndrome with oculorenal defect (Supportive), mode of inheritance: AR
- orofaciodigital syndrome III (Supportive), mode of inheritance: AR
- Joubert syndrome 20 (Definitive), mode of inheritance: AR
- Joubert syndrome 20 (Strong), mode of inheritance: AR
- ciliopathy (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Joubert syndrome 20; Meckel syndrome 11 | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal | 23012439; 23349226 |
| Conditions may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; |
ClinVar
This is a list of variants' phenotypes submitted to
- Joubert syndrome 20;Meckel syndrome, type 11 (172 variants)
- Meckel syndrome, type 11;Joubert syndrome 20 (134 variants)
- not provided (80 variants)
- Inborn genetic diseases (36 variants)
- not specified (28 variants)
- Joubert syndrome 20 (10 variants)
- Joubert syndrome and related disorders (8 variants)
- Meckel syndrome, type 11 (7 variants)
- Orofacial-digital syndrome III (1 variants)
- Congenital anomaly of kidney and urinary tract (1 variants)
- Ciliopathy (1 variants)
- Normal pregnancy (1 variants)
- Familial aplasia of the vermis (1 variants)
- Meckel-Gruber syndrome (1 variants)
- TMEM231-related condition (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM231 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 67 | 75 | ||||
| missense | 139 | 12 | 157 | |||
| nonsense | 10 | |||||
| start loss | 3 | |||||
| frameshift | 6 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | |||||
| splice region ? | 2 | 3 | 8 | 5 | 2 | 20 |
| non coding ? | 19 | 33 | 23 | 78 | ||
| Total | 13 | 11 | 169 | 113 | 28 |
Highest pathogenic variant AF is 0.0000197
Variants in TMEM231
This is a list of pathogenic ClinVar variants found in the TMEM231 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TMEM231 | protein_coding | protein_coding | ENST00000568377 | 6 | 18170 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.14e-7 | 0.548 | 124611 | 0 | 24 | 124635 | 0.0000963 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.411 | 201 | 185 | 1.08 | 0.0000102 | 2179 |
| Missense in Polyphen | 64 | 64.723 | 0.98883 | 824 | ||
| Synonymous | -0.680 | 89 | 81.2 | 1.10 | 0.00000506 | 704 |
| Loss of Function | 0.933 | 12 | 16.0 | 0.748 | 0.00000105 | 149 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000123 | 0.000123 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000112 | 0.000111 |
| Finnish | 0.000139 | 0.000139 |
| European (Non-Finnish) | 0.0000728 | 0.0000708 |
| Middle Eastern | 0.000112 | 0.000111 |
| South Asian | 0.000229 | 0.000229 |
| Other | 0.000166 | 0.000165 |
dbNSFP
Source:
- Function
- FUNCTION: Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Joubert syndrome 20 (JBTS20) [MIM:614970]: 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:23012439, ECO:0000269|PubMed:26477546}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Meckel syndrome 11 (MKS11) [MIM:615397]: 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:23349226}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Haploinsufficiency Scores
- pHI
- hipred
- N
- hipred_score
- 0.139
- ghis
- 0.399
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tmem231
- Phenotype
- limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype;
Gene ontology
- Biological process
- in utero embryonic development;vasculature development;smoothened signaling pathway;regulation of protein localization;embryonic digit morphogenesis;camera-type eye development;cilium assembly;neuroepithelial cell differentiation
- Cellular component
- integral component of membrane;ciliary transition zone;MKS complex;ciliary membrane
- Molecular function
- protein binding