HAND2
Chr 4heart and neural crest derivatives expressed 2
Also known as: DHAND2, Hed, Thing2, bHLHa26, dHand
HAND2 encodes a basic helix-loop-helix transcription factor that is essential for cardiac morphogenesis, particularly formation of the right ventricle and aortic arch arteries, and also regulates limb development and branchial arch formation. Mutations cause congenital heart defects and limb malformations with autosomal dominant inheritance. The gene has moderate constraint against loss-of-function variants, and clinical manifestations are typically apparent at birth due to structural abnormalities.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
150 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 | 61 | 0 | 61 |
Likely Pathogenic | 0 | 0 | 3 | 1 | 4 |
VUS | 4 | 42 | 15 | 0 | 61 |
Likely Benign | 0 | 3 | 2 | 10 | 15 |
Benign | 0 | 1 | 1 | 4 | 6 |
Conflicting | — | 1 | |||
| Total | 4 | 46 | 82 | 15 | 148 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HAND2 · 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