TMEM231

Chr 16AR

transmembrane protein 231

Also known as: ALYE870, JBTS20, MKS11, PRO1886

NCBI Gene: 79583ENSG00000205084UniProt: Q9H6L2

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]

Primary Disease Associations & Inheritance

Joubert syndrome 20MIM #614970
AR
Meckel syndrome 11MIM #615397
AR
590
ClinVar variants
89
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TMEM231
🧬
Gene-Disease Validity (ClinGen)
ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
89 Pathogenic / Likely Pathogenic· 263 VUS of 590 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.41Z-score
OE missense 1.08 (0.97–1.22)
201 obs / 185.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.75 (0.48–1.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.08 (0.97–1.22)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 12 / 16.0Missense obs/exp: 201 / 185.3Syn Z: -0.68

ClinVar Variant Classifications

590 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic63
Likely Pathogenic26
VUS263
Likely Benign177
Benign33
Conflicting28
63
Pathogenic
26
Likely Pathogenic
263
VUS
177
Likely Benign
33
Benign
28
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
4
45
1
63
Likely Pathogenic
13
5
8
0
26
VUS
1
213
44
5
263
Likely Benign
1
20
51
105
177
Benign
0
1
28
4
33
Conflicting
—28
Total28243176115590

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM231 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TMEM231-related Joubert syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Joubert syndrome 20

MIM #614970

Molecular basis of disorder known

Autosomal recessive

Meckel syndrome 11

MIM #615397

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TMEM231
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Long-read nanopore sequencing resolves a TMEM231 gene conversion event causing Meckel-Gruber syndrome.
Watson CM et al.·Hum Mutat
2020
Mutations in TMEM231 cause Joubert syndrome in French Canadians.
Srour M et al.·J Med Genet
2012
Fifteen years of research on oral-facial-digital syndromes: from 1 to 16 causal genes.
Bruel AL et al.·J Med Genet
2017Review
Whole-exome sequencing screening for candidate genes and potential pathogenic variants associated with early-onset high myopia in 47 Chinese families.
Rui X et al.·Sci Rep
2025
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
Li C et al.·PLoS Biol
2016
The diagnostic yield of whole exome sequencing as a first approach in consanguineous Omani renal ciliopathy syndrome patients.
Al Alawi I et al.·F1000Res
2021Cohort
Tectocerebellar dysraphia with occipital encephalocele: a phenotypic variant of the TMEM231 gene mutation induced Joubert syndrome.
Nicolas-Jilwan M et al.·Childs Nerv Syst
2019Case report
High Functioning Autism with Missense Mutations in Synaptotagmin-Like Protein 4 (SYTL4) and Transmembrane Protein 187 (TMEM187) Genes: SYTL4- Protein Modeling, Protein-Protein Interaction, Expression Profiling and MicroRNA Studies.
Rafi SK et al.·Int J Mol Sci
2019Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools