HELLS

Chr 10

helicase, lymphoid specific

Also known as: ICF4, LSH, Nbla10143, PASG, SALNR, SMARCA6

NCBI Gene: 3070 ENSG00000119969 UniProt: Q9NRZ9

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a lymphoid-specific helicase. Other helicases function in processes involving DNA strand separation, including replication, repair, recombination, and transcription. This protein is thought to be involved with cellular proliferation and may play a role in leukemogenesis. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2014]

ResearchGenerating clinical summary…

LOEUF 0.24

Clinical Summary— HELLS

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Gene-Disease Validity (ClinGen)

immunodeficiency-centromeric instability-facial anomalies syndrome 4 · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

20 unique Pathogenic / Likely Pathogenic· 161 VUS of 480 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.24LOEUF

pLI 1.000

Z-score 6.01

OE 0.13 (0.07–0.24)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.99Z-score

OE missense 0.60 (0.54–0.66)

258 obs / 433.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.24)

0≤0.351.4

Missense OE?0.60 (0.54–0.66)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 7 / 55.1Missense obs/exp: 258 / 433.3Syn Z: -0.15

ClinVar Variant Classifications

480 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic5

VUS161

Likely Benign261

Benign21

Conflicting4

Pathogenic

Likely Pathogenic

161

VUS

261

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	1	0	0	15
Likely Pathogenic	4	1	0	0	5
VUS	1	150	9	1	161
Likely Benign	0	7	131	123	261
Benign	0	0	15	6	21
Conflicting	—				4
Total	19	159	155	130	467

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

21 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap HELLS — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →