TMEM249
Chr 8catsper channel auxiliary subunit theta
Also known as: C8ORFK29, TMEM249
The protein is an auxiliary component of the CatSper complex that is involved in sperm cell hyperactivation and is predicted to be located in the sperm principal piece. Based on the available data, no human diseases have been definitively associated with TMEM249 mutations. The gene shows moderate tolerance to loss-of-function variants (pLI 0.10, LOEUF 0.85), suggesting it may not be highly constrained in humans.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
36 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 22 |
Likely Pathogenic | — | — | — | — | 2 |
VUS | — | — | — | — | 10 |
Likely Benign | — | — | — | — | 1 |
Benign | — | — | — | — | 1 |
| Total | — | 36 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TMEM249 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →No open access results found
External Resources
Links to major genomics databases and tools