TMCO2

Chr 1

transmembrane and coiled-coil domains 2

Also known as: dJ39G22.2

NCBI Gene: 127391ENSG00000188800UniProt: Q7Z6W1OMIM: 621569

TMCO2 encodes a nuclear protein whose specific function remains unclear. Mutations cause autosomal recessive cerebrofaciothoracic dysplasia, a severe developmental disorder characterized by craniofacial abnormalities, thoracic malformations, and neurological features. The gene shows minimal constraint against loss-of-function variants (pLI <0.001), consistent with its autosomal recessive inheritance pattern.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.57
Clinical Summary— TMCO2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 22 VUS of 32 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
1.57LOEUF
pLI 0.000
Z-score 0.40
OE 0.85 (0.48–1.57)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.41Z-score
OE missense 0.88 (0.73–1.06)
78 obs / 88.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.85 (0.48–1.57)
0≤0.351.4
Missense OE0.88 (0.73–1.06)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 7 / 8.2Missense obs/exp: 78 / 88.9Syn Z: 0.31
DN
0.85top 5%
GOF
0.75top 25%
LOF
0.2484th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

32 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS22
6
Pathogenic
2
Likely Pathogenic
22
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
0
18
4
0
22
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total01812030

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

View in ClinVar →

Protein Context — Lollipop Plot

TMCO2 · 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 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Identification of TMCO2 as an acrosome-associated protein during rat spermiogenesis.
Kaneko T et al.·Mol Reprod Dev
2020
Parimagnetism in HoCo2 and TmCo2.
Bonilla CM et al.·J Phys Condens Matter
2014
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