TCIRG1
Chr 11ART cell immune regulator 1, ATPase H+ transporting V0 subunit a3
Also known as: ATP6N1C, ATP6V0A3, Atp6i, OC-116kDa, OC116, OPTB1, Stv1, TIRC7
This protein is a subunit of the vacuolar H+-ATPase complex that pumps protons across membranes to regulate cellular and extracellular pH, which is essential for processes like protein sorting and receptor-mediated endocytosis. Mutations cause autosomal recessive infantile malignant osteopetrosis, a severe bone disease with early onset that affects bone resorption and can involve immune dysfunction. The gene shows very low constraint against loss-of-function variants in the general population.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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.
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
600 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 | 29 | 0 | 1 | 0 | 30 |
Likely Pathogenic | 42 | 3 | 2 | 0 | 47 |
VUS | 4 | 235 | 25 | 13 | 277 |
Likely Benign | 0 | 1 | 125 | 104 | 230 |
Benign | 0 | 0 | 2 | 0 | 2 |
Conflicting | — | 2 | |||
| Total | 75 | 239 | 155 | 117 | 588 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TCIRG1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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 →External Resources
Links to major genomics databases and tools