TBC1D14
Chr 4TBC1 domain family member 14
The TBC1D14 protein regulates autophagosome formation during cellular starvation and controls trafficking of ATG9 from recycling endosomes to the Golgi apparatus to maintain the autophagy initiation machinery. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy. The gene is highly constrained against loss-of-function variants (LOEUF 0.457), indicating intolerance to protein-disrupting mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
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
206 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 | 81 | 0 | 81 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 88 | 3 | 0 | 91 |
Likely Benign | 0 | 4 | 0 | 0 | 4 |
Benign | 0 | 1 | 0 | 1 | 2 |
| Total | 0 | 93 | 88 | 1 | 182 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TBC1D14 · 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