HELLS
Chr 10ARhelicase, lymphoid specific
Also known as: ICF4, LSH, Nbla10143, PASG, SALNR, SMARCA6
This gene encodes an ATP-dependent chromatin remodeler that regulates chromatin accessibility, DNA methylation, and histone modifications, and is involved in DNA repair and genomic stability. Mutations cause immunodeficiency-centromeric instability-facial anomalies syndrome 4, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (pLI = 1.00, LOEUF = 0.24), indicating that complete loss of protein function is poorly tolerated.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
ClinVar Variant Classifications
499 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 | 10 | 0 | 16 | 0 | 26 |
Likely Pathogenic | 4 | 0 | 1 | 0 | 5 |
VUS | 1 | 150 | 17 | 1 | 169 |
Likely Benign | 0 | 7 | 131 | 123 | 261 |
Benign | 0 | 0 | 15 | 6 | 21 |
Conflicting | — | 4 | |||
| Total | 15 | 157 | 180 | 130 | 486 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HELLS · 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