TMEM237

transmembrane protein 237

Basic information

Region (hg38): 2:201620183-201643570

Previous symbols: [ "ALS2CR4" ]

Links

ENSG00000155755 ∙ NCBI:65062 ∙ OMIM:614423 ∙ HGNC:14432 ∙ Uniprot:Q96Q45 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome 14 (Definitive), mode of inheritance: AR
• Joubert syndrome 14 (Moderate), mode of inheritance: AR
• Meckel syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome with oculorenal defect (Supportive), mode of inheritance: AR
• Joubert syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome with renal defect (Supportive), mode of inheritance: AR
• Joubert syndrome 14 (Strong), mode of inheritance: AR
• Joubert syndrome 14 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 14	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal	17603801; 20301500; 22152675
The condition 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 TMEM237 gene.

• Joubert syndrome 14 (357 variants)
• not provided (79 variants)
• not specified (34 variants)
• Inborn genetic diseases (14 variants)
• Familial aplasia of the vermis (7 variants)
• TMEM237-related condition (6 variants)
• Joubert syndrome and related disorders (4 variants)
• Joubert syndrome 1 (1 variants)
• Meckel-Gruber syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM237 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			3	33	2	38
missense		1	124	3	1	129
nonsense	7	3	1			11
start loss			1			1
frameshift	7	5	2			14
inframe indel			2			2
splice donor/acceptor (+/-2bp)	4	5	3			12
splice region			12	16	2	30
non coding	1		64	78	28	171
Total	19	14	200	114	31

Highest pathogenic variant AF is 0.0000592

Variants in TMEM237

This is a list of pathogenic ClinVar variants found in the TMEM237 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-201620235-A-T		Joubert syndrome 14	Uncertain significance (Jan 13, 2018)
2-201620258-T-C		Joubert syndrome 14	Uncertain significance (Jan 13, 2018)
2-201620263-T-C		Joubert syndrome 14	Uncertain significance (Jan 12, 2018)
2-201620400-T-C		Joubert syndrome 14	Uncertain significance (Jan 12, 2018)
2-201620527-T-C		Joubert syndrome 14	Uncertain significance (Jan 13, 2018)
2-201620558-C-T		Joubert syndrome 14	Uncertain significance (Jan 13, 2018)
2-201620738-T-C		Joubert syndrome 14	Uncertain significance (Jan 13, 2018)
2-201620741-TA-T		Familial aplasia of the vermis	Uncertain significance (Jun 14, 2016)
2-201620802-A-C		Joubert syndrome 14	Likely benign (Jan 12, 2018)
2-201620870-G-A		Joubert syndrome 14	Uncertain significance (Jan 13, 2018)
2-201620883-G-A		Joubert syndrome 14	Likely benign (Jan 13, 2018)
2-201620905-T-A		Joubert syndrome 14	Uncertain significance (Jan 13, 2018)
2-201621131-T-A		Joubert syndrome 14	Likely benign (Jan 13, 2018)
2-201621132-A-T		Joubert syndrome 14	Uncertain significance (Jan 12, 2018)
2-201621242-T-C		Joubert syndrome 14	Uncertain significance (Jan 12, 2018)
2-201621291-A-T		Joubert syndrome 14	Uncertain significance (Jan 12, 2018)
2-201621295-G-T		Joubert syndrome 14	Uncertain significance (Jan 12, 2018)
2-201621536-C-T		Joubert syndrome 14	Likely benign (Jan 12, 2018)
2-201621573-C-G		Joubert syndrome 14	Uncertain significance (Jan 13, 2018)
2-201621585-G-A		Joubert syndrome 14	Uncertain significance (Jan 13, 2018)
2-201621603-T-C		Joubert syndrome 14	Uncertain significance (Jan 13, 2018)
2-201621629-A-G		Joubert syndrome 14	Uncertain significance (Jan 13, 2018)
2-201621673-C-A		Joubert syndrome 14	Uncertain significance (Jan 12, 2018)
2-201621760-G-C		Joubert syndrome 14	Uncertain significance (Jan 13, 2018)
2-201621775-A-C		Joubert syndrome 14	Likely benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM237	protein_coding	protein_coding	ENST00000409883	13	23387

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.87e-12	0.114	124587	0	51	124638	0.000205

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0945	189	193	0.981	0.00000959	2582
Missense in Polyphen		68	66.919	1.0162		905
Synonymous	2.55	41	67.7	0.606	0.00000316	803
Loss of Function	0.639	20	23.3	0.857	0.00000132	283

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000479	0.000469
Ashkenazi Jewish	0.00	0.00
East Asian	0.000178	0.000167
Finnish	0.00	0.00
European (Non-Finnish)	0.000315	0.000310
Middle Eastern	0.000178	0.000167
South Asian	0.000106	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the transition zone in primary cilia. Required for ciliogenesis. {ECO:0000269|PubMed:22152675}.
• Disease: DISEASE: Joubert syndrome 14 (JBTS14) [MIM:614424]: An autosomal recessive disorder characterized by severe mental retardation, hypotonia, breathing abnormalities in infancy, and dysmorphic facial features. 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 renal disease, abnormal eye movements, and postaxial polydactyly. {ECO:0000269|PubMed:22152675}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.37

Haploinsufficiency Scores

• pHI: 0.0846
• hipred: N
• hipred_score: 0.167
• ghis: 0.498

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: Tmem237

Gene ontology

• Biological process: regulation of Wnt signaling pathway;cilium assembly
• Cellular component: membrane;integral component of membrane;ciliary transition zone
• Molecular function: protein binding