FAHD2B
Chr 2fumarylacetoacetate hydrolase domain containing 2B
FAHD2B encodes a mitochondrial tautomerase that converts enol-oxaloacetate to keto-oxaloacetate, preventing inhibition of succinate dehydrogenase and maintaining efficient aerobic respiration. Mutations cause autosomal recessive mitochondrial complex II deficiency with early-onset developmental delays, seizures, and metabolic acidosis. The gene is highly constrained against loss-of-function variants, indicating intolerance to haploinsufficiency.
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
111 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 | 19 | 0 | 19 |
Likely Pathogenic | 0 | 0 | 9 | 0 | 9 |
VUS | 0 | 47 | 22 | 0 | 69 |
Likely Benign | 0 | 3 | 2 | 0 | 5 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 50 | 53 | 0 | 103 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FAHD2B · 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 →No open access results found
External Resources
Links to major genomics databases and tools