TMEM187

Chr X

transmembrane protein 187

Also known as: CXorf12, DXS9878E, ITBA1

NCBI Gene: 8269ENSG00000177854UniProt: Q14656OMIM: 300059

This gene encodes a multi-pass membrane protein with unknown specific function. Mutations cause autosomal recessive developmental and epileptic encephalopathy with early infantile onset, characterized by severe intellectual disability, epilepsy, and developmental delays. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

OMIMResearchSummary from RefSeq
DNmechanismLOEUF 1.59
Clinical Summary— TMEM187
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
169 unique Pathogenic / Likely Pathogenic· 59 VUS of 250 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.59LOEUF
pLI 0.016
Z-score 0.68
OE 0.66 (0.30–1.59)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.14Z-score
OE missense 0.97 (0.84–1.12)
129 obs / 133.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.66 (0.30–1.59)
0≤0.351.4
Missense OE0.97 (0.84–1.12)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 3 / 4.6Missense obs/exp: 129 / 133.4Syn Z: -0.19
DN
0.7228th %ile
GOF
0.5758th %ile
LOF
0.2679th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

250 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic165
Likely Pathogenic4
VUS59
Likely Benign8
Benign2
Conflicting2
165
Pathogenic
4
Likely Pathogenic
59
VUS
8
Likely Benign
2
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
165
0
165
Likely Pathogenic
0
0
4
0
4
VUS
0
46
13
0
59
Likely Benign
0
6
0
2
8
Benign
0
1
0
1
2
Conflicting
—2
Total0531823240

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM187 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
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
Association of genetic variation on X chromosome with systemic lupus erythematosus in both Thai and Chinese populations.
Tangtanatakul P et al.·Lupus Sci Med
2024Meta-analysis
Integration of bioinformatics and machine learning approaches for the validation of pyrimidine metabolism-related genes and their implications in immunotherapy for osteoporosis.
Feng Z et al.·BMC Musculoskelet Disord
2024
Bioinformatics and machine learning were used to validate glutamine metabolism-related genes and immunotherapy in osteoporosis patients.
Wang L et al.·J Orthop Surg Res
2023Cohort
Meta-analysis of GWAS on two Chinese populations followed by replication identifies novel genetic variants on the X chromosome associated with systemic lupus erythematosus.
Zhang Y et al.·Hum Mol Genet
2015Meta-analysis
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients