TMEM60

Chr 7AR

transmembrane protein 60

Also known as: C7orf35, DC32

NCBI Gene: 85025ENSG00000135211UniProt: Q9H2L4

Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Structural heart defects and renal anomalies syndromeMIM #617478
AR
0
Active trials
16
Pathogenic / LP
43
ClinVar variants
0
Pubs (1 yr)
0.4
Missense Z
0.64
LOEUF
Clinical Summary— TMEM60
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 27 VUS of 43 total submissions
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.64LOEUF
pLI 0.755
Z-score 2.00
OE 0.00 (0.00–0.64)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
0.42Z-score
OE missense 0.86 (0.69–1.06)
58 obs / 67.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.64)
0≤0.351.4
Missense OE0.86 (0.69–1.06)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 0 / 4.7Missense obs/exp: 58 / 67.8Syn Z: 0.12
GOFDN
DN
0.6551th %ile
GOF
0.86top 5%
LOF
0.3843th %ile

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

GOFprediction above median
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

43 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS27
15
Pathogenic
1
Likely Pathogenic
27
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
20
7
0
27
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total02023043

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

View in ClinVar →

TMEM60 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 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