HUWE1
Chr XX-linkedHECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1
Also known as: ARF-BP1, HECTH9, HSPC272, Ib772, LASU1, MRXST, MULE, URE-B1
The protein functions as an E3 ubiquitin ligase that targets multiple proteins for degradation, including MCL1, p53, core histones, and MYCN, playing critical roles in apoptosis regulation, DNA repair, and neural development. Mutations cause X-linked syndromic intellectual developmental disorder, Turner type, with X-linked inheritance affecting primarily males. The gene is highly constrained against loss-of-function variants (pLI=1, LOEUF=0.06), indicating that functional copies are essential for normal development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
HUWE1 · 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