ANKRD26
Chr 10ADankyrin repeat domain 26
Also known as: THC2, bA145E8.1
The protein contains ankyrin repeats that mediate protein-protein interactions and regulates adipogenesis and feeding behavior. Mutations cause autosomal dominant thrombocytopenia-2, a bleeding disorder characterized by reduced platelet counts. This gene is not highly constrained against loss-of-function variants and has an established GeneReviews entry for clinical guidance.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports gain-of-function. 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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
500 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 | 0 | 0 | 0 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 11 | 295 | 19 | 1 | 326 |
Likely Benign | 0 | 11 | 19 | 122 | 152 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 4 | |||
| Total | 11 | 306 | 39 | 123 | 483 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ANKRD26 · 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
External Resources
Links to major genomics databases and tools