TMEM97
Chr 17transmembrane protein 97
Also known as: MAC30, S2R, sigma2R
TMEM97 encodes a sigma-2 receptor that regulates cellular cholesterol homeostasis by controlling cholesterol biosynthesis, trafficking, and lysosomal transport, and also functions in membrane trafficking and autophagy. The gene has high tolerance to loss-of-function variants (pLI 0.0003, LOEUF 1.495), and no established human disease phenotype has been reported in the literature. Pathogenic variants would likely follow a dominant-negative mechanism based on predictions.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
35 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 5 | 0 | 5 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 18 | 3 | 0 | 21 |
Likely Benign | 0 | 1 | 0 | 0 | 1 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 19 | 10 | 0 | 29 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TMEM97 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools