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HELB

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Summary

HELB (DNA helicase B, HGNC:17196) is a protein-coding gene on chromosome 12q14.3, encoding DNA helicase B (Q8NG08). 5’-3’ DNA helicase involved in DNA damage response by acting as an inhibitor of DNA end resection.

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.

Source: NCBI Gene 92797 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): familial ovarian carcinoma (Limited, GenCC)
  • GWAS associations: 6
  • Clinical variants (ClinVar): 184 total
  • MANE Select transcript: NM_001370285

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:17196
Approved symbolHELB
NameDNA helicase B
Location12q14.3
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000127311
Ensembl biotypeprotein_coding
OMIM614539
Entrez92797

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000247815, ENST00000440906, ENST00000536862, ENST00000542394, ENST00000545134, ENST00000545455, ENST00000897248, ENST00000921242

RefSeq mRNA: 2 — MANE Select: NM_001370285 NM_001370285, NM_033647

CCDS: CCDS8976

Canonical transcript exons

ENST00000247815 — 13 exons

ExonStartEnd
ENSE000007516166630634566306514
ENSE000007516206630473166305150
ENSE000008718376630970666310608
ENSE000012265656631398666314163
ENSE000022385666633800166338199
ENSE000023124196630249366302790
ENSE000035003626632398366324211
ENSE000035335816632272466322783
ENSE000035511426633115466331645
ENSE000036211276631863866318792
ENSE000036317566632194866322029
ENSE000036389876632498366325126
ENSE000036571986631524266315383

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 81.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.9660 / max 177.0152, expressed in 1372 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
1265553.14271085
1265562.8233938

Top tissues by expression

236 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047381.38gold quality
bone marrow cellCL:000209280.96gold quality
colonic epitheliumUBERON:000039775.05gold quality
leukocyteCL:000073875.04gold quality
monocyteCL:000057674.91gold quality
adrenal tissueUBERON:001830372.19gold quality
granulocyteCL:000009471.54gold quality
calcaneal tendonUBERON:000370170.87gold quality
vermiform appendixUBERON:000115470.49gold quality
bloodUBERON:000017870.48gold quality
lymph nodeUBERON:000002969.38gold quality
stromal cell of endometriumCL:000225568.07gold quality
ventricular zoneUBERON:000305366.86gold quality
ganglionic eminenceUBERON:000402366.47gold quality
tonsilUBERON:000237265.34gold quality
caecumUBERON:000115364.89gold quality
tendonUBERON:000004364.55gold quality
rectumUBERON:000105263.50gold quality
cortical plateUBERON:000534363.18gold quality
cardia of stomachUBERON:000116262.66silver quality
gall bladderUBERON:000211062.43gold quality
secondary oocyteCL:000065562.32silver quality
smooth muscle tissueUBERON:000113562.29gold quality
bone marrowUBERON:000237162.24gold quality
omental fat padUBERON:001041462.20gold quality
peritoneumUBERON:000235862.14gold quality
adipose tissue of abdominal regionUBERON:000780861.02gold quality
thymusUBERON:000237060.86gold quality
spleenUBERON:000210660.80gold quality
upper lobe of left lungUBERON:000895260.49gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

ExperimentMarker?Max mean expression
E-GEOD-100618yes119.38
E-ANND-3yes5.33

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 8)

  • role of dominant-negative mutant in blocking onset of chromosomal DNA replication (PMID:12181327)
  • Replication stress-induced recruitment of HDHB to chromatin is independent of checkpoint signaling but correlates with the level of replication protein A (RPA) recruited to chromatin. (PMID:22194613)
  • HDHB promotes homologous recombination in vivo and stimulates 5’-3’ heteroduplex extension during Rad51-mediated strand exchange in vitro (PMID:25617833)
  • The depletion of HDHB from human cells diminishes Cdc45 association with chromatin, suggesting that HDHB may facilitate Cdc45 recruitment at G1/S in human cells. (PMID:25933514)
  • Conclude that mammalian DNA end resection triggers its own inhibition via the recruitment of HELB. (PMID:26774285)
  • Genome Maintenance by DNA Helicase B. (PMID:32455610)
  • The Expression of Human DNA Helicase B Is Affected by G-Quadruplexes in the Promoter. (PMID:32478505)
  • Human HELB is a processive motor protein that catalyzes RPA clearance from single-stranded DNA. (PMID:35385349)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriohelbENSDARG00000053127
mus_musculusHelbENSMUSG00000020228
rattus_norvegicusHelbENSRNOG00000004189

Paralogs (18): DHX33 (ENSG00000005100), YTHDC2 (ENSG00000047188), DHX29 (ENSG00000067248), DHX8 (ENSG00000067596), DHX32 (ENSG00000089876), DHX35 (ENSG00000101452), DHX40 (ENSG00000108406), DHX15 (ENSG00000109606), DHX30 (ENSG00000132153), DHX34 (ENSG00000134815), DHX9 (ENSG00000135829), DHX38 (ENSG00000140829), DQX1 (ENSG00000144045), DHX37 (ENSG00000150990), TDRD9 (ENSG00000156414), DHX57 (ENSG00000163214), DHX36 (ENSG00000174953), DHX16 (ENSG00000204560)

Protein

Protein identifiers

DNA helicase B — Q8NG08 (reviewed: Q8NG08)

All UniProt accessions (2): Q8NG08, F5H1I4

UniProt curated annotations — full annotation on UniProt →

Function. 5’-3’ DNA helicase involved in DNA damage response by acting as an inhibitor of DNA end resection. 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. As cells approach S phase, DNA end resection is promoted by the nuclear export of HELB following phosphorylation. Acts independently of TP53BP1. Unwinds duplex DNA with 5’-3’ polarity. Has single-strand DNA-dependent ATPase and DNA helicase activities. Prefers ATP and dATP as substrates. During S phase, may facilitate cellular recovery from replication stress.

Subunit / interactions. Binds to RPA1; this interaction promotes HELB recruitment to chromatin following DNA damage. Interacts with at least two subunits of the DNA polymerase alpha complex: Interacts with CDC45. Interacts with TOPB1.

Subcellular location. Nucleus. Cytoplasm. Chromosome.

Tissue specificity. Highly expressed in testis and thymus and weakly in liver, spleen, kidney and brain.

Post-translational modifications. Phosphorylated at Ser-967 by CDK2 during the G1/S transition, resulting in its nuclear export into the cytoplasm. As S phase progresses, its exclusion from the nucleus promotes the activation of long-range resection.

Activity regulation. Inhibited by salt concentration greater than 100 mM. Uses either magnesium or manganese ions to support helicase activity. Binds strongly to single-stranded DNA in the absence of ATP but dissociates readily in the presence of 1 mM ATP.

Similarity. Belongs to the RecD family. HELB subfamily.

Isoforms (2)

UniProt IDNamesCanonical?
Q8NG08-11yes
Q8NG08-22

RefSeq proteins (2): NP_001357214, NP_387467 (=MANE)

Domains & families (InterPro)

IDNameType
IPR027417P-loop_NTPaseHomologous_superfamily
IPR050534Coronavir_polyprotein_1abFamily
IPR058839WHD_HELBDomain

Pfam: PF13604, PF25894

Enzyme classification (BRENDA):

  • EC 3.6.4.12 — DNA helicase (BRENDA: 0 organisms, 0 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

  • ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (33 total): mutagenesis site 12, sequence variant 6, modified residue 5, region of interest 2, splice variant 2, sequence conflict 2, helix 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
7XV1X-RAY DIFFRACTION1.8

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q8NG08-F170.850.30

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 967, 971, 1027, 1048, 1058

Mutagenesis-validated functional residues (12):

PositionPhenotype
481no atpase activity.
499loss of rpa1-binding, leading to impaired recruitment to sites of double-strand breaks; when associated with a-506 and a
506loss of rpa1-binding, leading to impaired recruitment to sites of double-strand breaks; when associated with a-499 and a
510loss of rpa1-binding, leading to impaired recruitment to sites of double-strand breaks; when associated with a-499 and a
591no atpase activity.
967impaired phosphorylation, inducing accumulation in the nucleus.
967phosphomimetic mutant; leads to higher localization to the cytoplasm.
984does not affect subcellular location.
1005does not affect subcellular location.
1021does not affect subcellular location.
1061–1065accumulation in the nucleus due to defects in nuclear export.
1068–1070accumulation in the nucleus due to defects in nuclear export.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 134 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_DNA_REPAIR, GOCC_NUCLEAR_REPLICATION_FORK, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, DOUGLAS_BMI1_TARGETS_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, GOBP_RECOMBINATIONAL_REPAIR, MARKEY_RB1_ACUTE_LOF_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_DNA_DOUBLE_STRAND_BREAK_PROCESSING

GO Biological Process (7): DNA replication (GO:0006260), DNA replication, synthesis of primer (GO:0006269), DNA repair (GO:0006281), DNA damage response (GO:0006974), regulation of DNA double-strand break processing (GO:1903775), negative regulation of double-strand break repair via homologous recombination (GO:2000042), DNA-templated DNA replication (GO:0006261)

GO Molecular Function (9): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), single-stranded DNA helicase activity (GO:0017116), 5’-3’ DNA helicase activity (GO:0043139), protein-containing complex binding (GO:0044877), nucleotide binding (GO:0000166), DNA helicase activity (GO:0003678), helicase activity (GO:0004386), hydrolase activity (GO:0016787)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), nuclear body (GO:0016604), site of double-strand break (GO:0035861), DNA replication factor A complex (GO:0005662), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
DNA metabolic process2
ATP-dependent activity2
DNA helicase activity2
intracellular membrane-bounded organelle2
cytoplasm2
intracellular membraneless organelle2
DNA biosynthetic process1
DNA-templated DNA replication1
RNA biosynthetic process1
DNA damage response1
cellular response to stress1
DNA double-strand break processing1
regulation of DNA metabolic process1
double-strand break repair via homologous recombination1
regulation of double-strand break repair via homologous recombination1
negative regulation of DNA recombination1
negative regulation of double-strand break repair1
DNA replication1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
ribonucleoside triphosphate phosphatase activity1
binding1
nucleoside phosphate binding1
heterocyclic compound binding1
helicase activity1
ATP-dependent activity, acting on DNA1
nucleic acid conformation isomerase activity1
catalytic activity, acting on a nucleic acid1
catalytic activity1
nuclear lumen1
intracellular anatomical structure1
nucleoplasm1
site of DNA damage1
nuclear replisome1
nuclear protein-containing complex1

Protein interactions and networks

STRING

1600 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
HELBDNA2P51530625
HELBEXO1Q9UQ84490
HELBRAD52P43351464
HELBWRNQ14191460
HELBCDC45O75419456
HELBLLPHQ9BRT6430
HELBF5H6H0F5H6H0422
HELBTP53BP1Q12888414
HELBTOP3AQ13472411
HELBMCM10Q7L590405
HELBDDX31Q9H8H2404
HELBRPA1P27694393
HELBSSBP1Q04837379
HELBFANCMQ8IYD8372
HELBPIF1Q9H611371

IntAct

14 interactions, top by confidence:

ABTypeScore
RPA2RPA1psi-mi:“MI:0914”(association)0.960
RPA1RPA2psi-mi:“MI:0914”(association)0.960
RPA3RPA2psi-mi:“MI:0914”(association)0.930
POLR2EPOLR3Apsi-mi:“MI:0914”(association)0.870
WDR5MEN1psi-mi:“MI:0914”(association)0.710
Septin9SEPTIN8psi-mi:“MI:0914”(association)0.350
NEK4E2F8psi-mi:“MI:0914”(association)0.350
CCNA2TBC1D4psi-mi:“MI:0914”(association)0.350
SLC46A2SNAP23psi-mi:“MI:0914”(association)0.350
HELBpsi-mi:“MI:0915”(physical association)0.000

BioGRID (32): HELB (Affinity Capture-MS), HELB (Affinity Capture-MS), HELB (Affinity Capture-MS), HELB (Affinity Capture-MS), HELB (Affinity Capture-MS), HELB (Affinity Capture-MS), HELB (Affinity Capture-MS), HELB (Affinity Capture-RNA), HELB (Affinity Capture-MS), HELB (Proximity Label-MS), HELB (Co-fractionation), HINT2 (Co-fractionation), HELB (Affinity Capture-MS), HELB (Affinity Capture-MS), HELB (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2TTB3, A0JMR6, A4IIA7, F4JNY0, F6RRD7, I3XHK1, O60934, O88622, P14629, P28715, P79457, Q08DZ8, Q12789, Q17RS7, Q1LWH4, Q28I29, Q32PL8, Q3B7T1, Q4R7Q1, Q5FWP4, Q5M954, Q5QJC2, Q5RA37, Q5RCV3, Q5ZIN2, Q66J91, Q6GQV7, Q6NVF4, Q6P1E7, Q6P1H6, Q6P256, Q6P7W5, Q76CY8, Q7TP65, Q86W56, Q8BMI4, Q8C0W1, Q8C5W4, Q8GT06, Q8IXW5

Diamond homologs: A0QS28, P04993, P45158, P9WHJ0, P9WHJ1, Q44349, Q8NG08, Q9RT63, Q6NVF4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

184 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance157
Likely benign10
Benign5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2094 predictions. Top by Δscore:

VariantEffectΔscore
12:66302754:G:GTdonor_gain1.0000
12:66302754:G:Tdonor_gain1.0000
12:66302788:GCG:Gdonor_gain1.0000
12:66302791:G:GGdonor_gain1.0000
12:66302796:G:GTdonor_gain1.0000
12:66302797:A:Tdonor_gain1.0000
12:66306343:A:AGacceptor_gain1.0000
12:66306344:G:GGacceptor_gain1.0000
12:66315238:TTAG:Tacceptor_loss1.0000
12:66315239:TA:Tacceptor_loss1.0000
12:66315240:A:AGacceptor_gain1.0000
12:66315241:G:GAacceptor_loss1.0000
12:66315241:G:GGacceptor_gain1.0000
12:66315379:ACAAG:Adonor_loss1.0000
12:66315380:CAAGG:Cdonor_loss1.0000
12:66315381:AAGG:Adonor_loss1.0000
12:66315382:AGGT:Adonor_loss1.0000
12:66315383:GG:Gdonor_loss1.0000
12:66315384:G:GAdonor_loss1.0000
12:66315385:T:Adonor_loss1.0000
12:66318635:A:AGacceptor_gain1.0000
12:66318636:A:AGacceptor_gain1.0000
12:66318637:G:GGacceptor_gain1.0000
12:66318788:CTCTT:Cdonor_gain1.0000
12:66318789:TCTT:Tdonor_gain1.0000
12:66318791:TT:Tdonor_gain1.0000
12:66318791:TTGT:Tdonor_loss1.0000
12:66318792:TGTAA:Tdonor_loss1.0000
12:66318793:G:Cdonor_loss1.0000
12:66318793:G:GGdonor_gain1.0000

AlphaMissense

7223 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
12:66314082:A:CS593R0.997
12:66314084:T:AS593R0.997
12:66314084:T:GS593R0.997
12:66325100:T:AW882R0.997
12:66325100:T:CW882R0.997
12:66331227:C:AA915D0.997
12:66315262:A:CS627R0.995
12:66315264:T:AS627R0.995
12:66315264:T:GS627R0.995
12:66322022:T:CF744L0.995
12:66322024:T:AF744L0.995
12:66322024:T:GF744L0.995
12:66310348:A:CS474R0.994
12:66310350:T:AS474R0.994
12:66310350:T:GS474R0.994
12:66314079:G:AG592R0.994
12:66314079:G:CG592R0.994
12:66315245:A:TD621V0.994
12:66315257:T:CL625S0.994
12:66331312:A:CR943S0.994
12:66331312:A:TR943S0.994
12:66315245:A:CD621A0.993
12:66322014:T:CF741S0.993
12:66325121:T:CF889L0.993
12:66325123:T:AF889L0.993
12:66325123:T:GF889L0.993
12:66314065:T:CL587P0.992
12:66325115:C:GH887D0.992
12:66304802:T:AW87R0.991
12:66304802:T:CW87R0.991

dbSNP variants (sampled 300 via entrez): RS1000099779 (12:66338925 G>C), RS1000170727 (12:66320982 C>T), RS1000199284 (12:66303892 C>A), RS1000241561 (12:66318938 TAGTA>T), RS1000302631 (12:66326252 T>A,C), RS1000381502 (12:66314330 G>A), RS1000449860 (12:66305611 G>C), RS1000454001 (12:66332434 C>T), RS1000460136 (12:66307015 G>A), RS1000503481 (12:66305284 G>C), RS1000562752 (12:66319035 G>A), RS1000658496 (12:66311705 G>C), RS1000713887 (12:66312325 C>T), RS1000798067 (12:66305287 T>C), RS1000941947 (12:66337773 G>A,C)

Disease associations

OMIM: gene MIM:614539 | disease phenotypes:

GenCC curated gene-disease

DiseaseClassificationInheritance
familial ovarian carcinomaLimitedAutosomal dominant

Mondo (1): familial ovarian carcinoma (MONDO:0100514)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

StudyTraitp-value
GCST004618_36White blood cell count (basophil)1.000000e-14
GCST005312_28Menopause (age at onset)7.000000e-06
GCST005560_1Menopause (age at onset)1.000000e-31
GCST005976_21White blood cell count (basophil)2.000000e-10
GCST90002379_52Basophil count7.000000e-11
GCST90002380_107Basophil percentage of white cells4.000000e-12

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0005090basophil count
EFO:0004704age at menopause
EFO:0007992basophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs1168312HELB0.000

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

ChemicalActions (top 5)PubMed papers
FR900359decreases phosphorylation1
bisphenol Aincreases methylation1
beta-lapachonedecreases expression, increases expression1
arseniteaffects binding, decreases reaction1
di-n-butylphosphoric acidaffects expression1
abrineincreases expression1
jinfukangdecreases expression1
(+)-JQ1 compounddecreases expression1
Decitabineincreases expression1
Sunitinibincreases expression1
Amiodaroneincreases expression1
Benzo(a)pyrenedecreases expression1
Caffeineincreases phosphorylation1
Cannabidiolincreases expression1
Naledaffects expression1
Nickelincreases expression1
Valproic Acidaffects expression1
Cyclosporineincreases expression1
Antirheumatic Agentsdecreases expression1
Cadmium Chloridedecreases expression1
Okadaic Acidincreases expression1
Copper Sulfateincreases expression1
Particulate Matterdecreases expression, increases expression1

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

TrialPhaseStatusTitle
NCT01230346Not specifiedACTIVE_NOT_RECRUITINGCulturally-Informed Counseling in Latinas at High Risk for Hereditary Breast or Ovarian Cancer
NCT04125914Not specifiedACTIVE_NOT_RECRUITINGWeight Management and Health Behavior Intervention in Lowering Cancer Risk for BRCA Positive and Lynch Syndrome Families

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot