TMEM231

Chr 16AR

transmembrane protein 231

Also known as: ALYE870, JBTS20, MKS11, PRO1886

NCBI Gene: 79583 ENSG00000205084 UniProt: Q9H6L2 OMIM: 614949

This gene encodes a transmembrane component of the tectonic-like complex that acts as a barrier preventing diffusion of transmembrane proteins between the cilia and plasma membranes, and is required for ciliogenesis and sonic hedgehog signaling. Mutations cause Joubert syndrome and Meckel syndrome, both severe ciliopathies affecting the brain, kidneys, liver, and other organ systems. The gene follows autosomal recessive inheritance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a transmembrane protein, which is a component of the B9 complex involved in the formation of the diffusion barrier between the cilia and plasma membrane. Mutations in this gene cause Joubert syndrome (JBTS). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.212 OMIM phenotypes

Clinical Summary— TMEM231

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Gene-Disease Validity (ClinGen)

ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

60 unique Pathogenic / Likely Pathogenic· 242 VUS of 540 total submissions

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GeneReview available — TMEM231

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.21LOEUF

pLI 0.000

Z-score 0.93

OE 0.75 (0.48–1.21)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.41Z-score

OE missense 1.08 (0.97–1.22)

201 obs / 185.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.75 (0.48–1.21)

0≤0.351.4

Missense OE?1.08 (0.97–1.22)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 12 / 16.0Missense obs/exp: 201 / 185.3Syn Z: -0.68

ClinVar Variant Classifications

540 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35

Likely Pathogenic25

VUS242

Likely Benign175

Benign32

Conflicting27

Pathogenic

Likely Pathogenic

242

VUS

175

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	26	2	7	0	35
Likely Pathogenic	20	4	1	0	25
VUS	5	214	18	5	242
Likely Benign	1	20	49	105	175
Benign	0	1	27	4	32
Conflicting	—				27
Total	52	241	102	114	536

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

29 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap TMEM231 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →