TAC4
Chr 17tachykinin precursor 4
Also known as: EK, HK-1, HK1, PPT-C
TAC4 encodes a tachykinin neurotransmitter that activates tachykinin receptor 1 to regulate blood pressure, immune function, endocrine secretion, pain perception, and smooth muscle contraction through its cleavage products endokinin-A and endokinin-C. Pathogenic variants cause disease through a dominant-negative mechanism, though specific clinical phenotypes associated with TAC4 mutations are not well-established. The gene shows tolerance to loss-of-function variants, suggesting haploinsufficiency is unlikely to be pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
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.
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
30 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 | 10 | 0 | 10 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 9 | 0 | 0 | 9 |
Likely Benign | 0 | 1 | 0 | 0 | 1 |
Benign | 1 | 0 | 1 | 0 | 2 |
| Total | 1 | 10 | 12 | 0 | 23 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TAC4 · 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 →External Resources
Links to major genomics databases and tools