HELB

protein-coding

DNA helicase B

Gene summary

This gene encodes a DNA-dependent ATPase which catalyzes the unwinding of DNA necessary for DNA replication, repair, recombination, and transcription. This gene is thought to function specifically during the S phase entry of the cell cycle. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

MANE transcript

NM_001370285.1

Inheritance

ClinVar variants

U:162B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr12:66,302,493-66,343,643

External References & Databases

Ensembl (ENSG00000127311)

Transcript & Mutation Effects

hg38 • Region Span ~41.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial ovarian carcinomaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100514

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HELB variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 167

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001370285.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			160 clinvar	10 clinvar	4 clinvar	174
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	162	10	5	177

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001370285.1	RefSeq	NP_001357214.1	13	MANE Select
ENST00000247815.9	Ensembl	ENSP00000247815.5	13	MANE Select
NM_033647.5	RefSeq	NP_387467.2	13	Standard
ENST00000440906.6	Ensembl	ENSP00000396955.2	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

DNA replication
DNA replication, synthesis of RNA primer
DNA repair
cellular response to DNA damage stimulus
DNA duplex unwinding

Molecular Function

RNA binding
ATP binding
single-stranded DNA-dependent ATP-dependent DNA helicase activity
ATP-dependent 5'-3' DNA helicase activity
protein-containing complex binding

Cellular Component

nucleus
DNA replication factor A complex
cytoplasm
site of double-strand break

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000247815
Coding exons: 13
Length: 41099
Individuals with no LoFs: 120992
Homozygous LoFs: 46
Heterozygous LoFs: 4710
Defined: 125748
p: 0.0191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.393	545	571	0.954	0.0000289	7180
Missense (PolyPhen)		167	175.07	0.95391		2253
Synonymous	0.650	199	211	0.943	0.0000114	2024
Loss of Function	0.602	41	45.4	0.904	0.00000231	581

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0048	0.0047	notable
Latino/Admixed American	0.013	0.013	notable
Ashkenazi Jewish	0.021	0.021	notable
East Asian	0.0021	0.0020	notable
Finnish	0.021	0.021	notable
European (Non-Finnish)	0.027	0.027	notable
South Asian	0.013	0.013	notable
Other	0.023	0.023	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: 5'-3' DNA helicase involved in DNA damage response by acting as an inhibitor of DNA end resection (PubMed:25617833, PubMed:26774285). Recruitment to single-stranded DNA (ssDNA) following DNA damage leads to inhibit the nucleases catalyzing resection, such as EXO1, BLM and DNA2, possibly via the 5'-3' ssDNA translocase activity of HELB (PubMed:26774285). As cells approach S phase, DNA end resection is promoted by the nuclear export of HELB following phosphorylation (PubMed:26774285). Acts independently of TP53BP1 (PubMed:26774285). Unwinds duplex DNA with 5'-3' polarity. Has single-strand DNA-dependent ATPase and DNA helicase activities. Prefers ATP and dATP as substrates (PubMed:12181327). During S phase, may facilitate cellular recovery from replication stress (PubMed:22194613). {ECO:0000269|PubMed:12181327, ECO:0000269|PubMed:22194613, ECO:0000269|PubMed:25617833, ECO:0000269|PubMed:26774285}.;

Recessive Scores

pRec: 0.0986

Intolerance Scores

LoFtool: 0.969
RVIS EVS: 1.08
RVIS percentile EVS: 91.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.845

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	High	High