KCTD12
Chr 13potassium channel tetramerization domain containing 12
Also known as: C13orf2, PFET1, PFETIN
KCTD12 encodes an auxiliary subunit of GABA-B receptors that regulates receptor pharmacology, kinetics, and G-protein signaling by accelerating onset and promoting desensitization. Mutations cause neurodevelopmental disorders with epilepsy, developmental delay, and intellectual disability, typically with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants, suggesting that complete loss of function may be compatible with survival but still pathogenic.
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
119 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 | 72 | 0 | 72 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 38 | 6 | 0 | 44 |
Likely Benign | 0 | 1 | 0 | 0 | 1 |
Benign | 0 | 0 | 0 | 2 | 2 |
| Total | 0 | 39 | 78 | 2 | 119 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KCTD12 · 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