HARS1
Chr 5ADARhistidyl-tRNA synthetase 1
Also known as: CMT2W, HARS, HRS, USH3B
The protein encoded by HARS1 is a cytoplasmic aminoacyl-tRNA synthetase that synthesizes histidyl-transfer RNA, essential for incorporating histidine into proteins during translation. Mutations cause Charcot-Marie-Tooth disease axonal type 2W (autosomal dominant) and Usher syndrome type 3B (autosomal recessive). The pathogenic mechanism appears to involve dominant-negative effects for the dominant form, while the recessive form likely results from loss of enzymatic function.
Refuted — evidence has disproved this relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
HARS1 · 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