TMEM231

transmembrane protein 231, the group of MKS complex

Basic information

Region (hg38): 16:75536741-75556289

Links

ENSG00000205084 ∙ NCBI:79583 ∙ OMIM:614949 ∙ HGNC:37234 ∙ Uniprot:Q9H6L2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the TMEM231 gene.

• Meckel_syndrome,_type_11 (375 variants)
• Joubert_syndrome_20 (374 variants)
• not_provided (83 variants)
• Inborn_genetic_diseases (67 variants)
• not_specified (25 variants)
• TMEM231-related_disorder (22 variants)
• Joubert_syndrome_and_related_disorders (10 variants)
• Ciliopathy (3 variants)
• Orofacial-digital_syndrome_III (1 variants)
• Meckel-Gruber_syndrome (1 variants)
• Congenital_anomaly_of_kidney_and_urinary_tract (1 variants)
• Joubert_syndrome (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. These statistics are base on transcript: NM_001077418.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		17	83	2	103
missense	6	6	163	21		196
nonsense	4	4	4			12
start loss				1		1
frameshift	5	7				12
splice donor/acceptor (+/-2bp)	5	7	1	1		14
Total	21	24	185	106	2

Highest pathogenic variant AF is 0.000286068

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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