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Atlas / Gene / HELT

HELT

gene
On this page

Also known as HESLHCM1228MgnbHLHb44MEGANE

Summary

HELT (helt bHLH transcription factor, HGNC:33783) is a protein-coding gene on chromosome 4q35.1, encoding Hairy and enhancer of split-related protein HELT (A6NFD8). Transcriptional repressor which binds preferentially to the canonical E box sequence 5’-CACGCG-3'.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of neurogenesis. Predicted to act upstream of or within several processes, including nervous system development; regulation of transcription by RNA polymerase II; and suckling behavior. Predicted to be located in chromatin. Predicted to be part of transcription regulator complex. Predicted to be active in nucleus.

Source: NCBI Gene 391723 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 70 total
  • MANE Select transcript: NM_001300781

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:33783
Approved symbolHELT
Namehelt bHLH transcription factor
Location4q35.1
Locus typegene with protein product
StatusApproved
AliasesHESL, HCM1228, Mgn, bHLHb44, MEGANE
Ensembl geneENSG00000187821
Ensembl biotypeprotein_coding
OMIM617546
Entrez391723

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000338875, ENST00000505610, ENST00000513599, ENST00000515777

RefSeq mRNA: 2 — MANE Select: NM_001300781 NM_001300781, NM_001300782

CCDS: CCDS75214, CCDS75215

Canonical transcript exons

ENST00000515777 — 4 exons

ExonStartEnd
ENSE00001384651185019387185019491
ENSE00002050326185019747185019843
ENSE00003928994185020273185020953
ENSE00003932612185018490185018955

Expression profiles

Bgee: expression breadth broad, 24 present calls, max score 60.28.

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
skin of legUBERON:000151160.28gold quality
zone of skinUBERON:000001459.08gold quality
skin of abdomenUBERON:000141658.11gold quality
right lungUBERON:000216756.73gold quality
metanephros cortexUBERON:001053354.41gold quality
adult mammalian kidneyUBERON:000008252.81gold quality
kidneyUBERON:000211348.33gold quality
sural nerveUBERON:001548844.10gold quality
cortex of kidneyUBERON:000122543.94gold quality
upper lobe of left lungUBERON:000895243.29gold quality
lungUBERON:000204840.32gold quality
spleenUBERON:000210639.74gold quality
bone marrow cellCL:000209238.23gold quality
ganglionic eminenceUBERON:000402338.18gold quality
colonic epitheliumUBERON:000039737.20gold quality
body of stomachUBERON:000116136.89gold quality
ventricular zoneUBERON:000305336.48gold quality
cortical plateUBERON:000534336.47gold quality
stomachUBERON:000094535.78gold quality
skeletal muscle tissueUBERON:000113434.85gold quality
fundus of stomachUBERON:000116034.38gold quality
bone marrowUBERON:000237132.80gold quality
hindlimb stylopod muscleUBERON:000425232.15gold quality
muscle tissueUBERON:000238532.14gold quality
prefrontal cortexUBERON:000045130.88gold quality
stromal cell of endometriumCL:000225529.87gold quality
liverUBERON:000210729.67gold quality
monocyteCL:000057628.24gold quality
leukocyteCL:000073828.18gold quality
duodenumUBERON:000211428.14gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-ANND-3no0.20

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

TargetRegulation
HELT

JASPAR motifs

MotifNameFamily
MA2628.1HELTHairy-related factors

JASPAR matrix evidence (PMIDs): PMID:14764602

Upstream regulators (CollecTRI, top): DACH2, FOXA1, FOXA2, HELT

Literature-anchored findings (GeneRIF, showing 2)

  • identified and characterized human HES-like (HESL), rat hesl, and rainbow trout hesl genes by using bioinformatics (PMID:15375612)
  • Activation of DPF3a upon hypertrophic stimuli in cardiac hypertrophy switches cardiac fetal gene expression from being silenced by HEY to being activated by BRG1. (PMID:26582913)

Cross-species orthologs

12 orthologs

OrganismSymbolGene ID
danio_rerioheltENSDARG00000056400
mus_musculusHeltENSMUSG00000047171
rattus_norvegicusHeltENSRNOG00000010785
drosophila_melanogasterE(spl)m8-HLHFBGN0000591
drosophila_melanogasterE(spl)m3-HLHFBGN0002609
drosophila_melanogasterE(spl)m5-HLHFBGN0002631
drosophila_melanogasterE(spl)m7-HLHFBGN0002633
drosophila_melanogasterE(spl)mbeta-HLHFBGN0002733
drosophila_melanogasterE(spl)mdelta-HLHFBGN0002734
drosophila_melanogasterE(spl)mgamma-HLHFBGN0002735
drosophila_melanogasterHesrFBGN0030899
drosophila_melanogastercwoFBGN0259938

Paralogs (12): HES2 (ENSG00000069812), HES1 (ENSG00000114315), BHLHE41 (ENSG00000123095), BHLHE40 (ENSG00000134107), HEY2 (ENSG00000135547), HES6 (ENSG00000144485), HEYL (ENSG00000163909), HEY1 (ENSG00000164683), HES3 (ENSG00000173673), HES7 (ENSG00000179111), HES4 (ENSG00000188290), HES5 (ENSG00000197921)

Protein

Protein identifiers

Hairy and enhancer of split-related protein HELT — A6NFD8 (reviewed: A6NFD8)

Alternative names: HES/HEY-like transcription factor

All UniProt accessions (2): A0A087WSW0, A6NFD8

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor which binds preferentially to the canonical E box sequence 5’-CACGCG-3'.

Subunit / interactions. Self-associates. Interacts with HES5 and HEY2.

Subcellular location. Nucleus.

Similarity. Belongs to the HEY family.

Isoforms (2)

UniProt IDNamesCanonical?
A6NFD8-31yes
A6NFD8-42

RefSeq proteins (2): NP_001287710, NP_001287711 (=MANE)

Domains & families (InterPro)

IDNameType
IPR003650Orange_domDomain
IPR011598bHLH_domDomain
IPR036638HLH_DNA-bd_sfHomologous_superfamily
IPR050370HES_HEYFamily

Pfam: PF00010, PF07527

UniProt features (6 total): domain 2, chain 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-A6NFD8-F166.940.31

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 (1): 48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 44 (showing top): GOBP_BEHAVIOR, GOBP_SUCKLING_BEHAVIOR, GOBP_GROWTH, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_GABAERGIC_NEURON_DIFFERENTIATION, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GROSS_ELK3_TARGETS_DN, GROSS_HIF1A_TARGETS_DN, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_UP, GOBP_MULTICELLULAR_ORGANISM_GROWTH, chr4q35, GOBP_REGULATION_OF_CELL_DEVELOPMENT, GOBP_POST_EMBRYONIC_DEVELOPMENT, KONDO_PROSTATE_CANCER_HCP_WITH_H3K27ME3

GO Biological Process (14): suckling behavior (GO:0001967), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), central nervous system development (GO:0007417), post-embryonic development (GO:0009791), anterior/posterior pattern specification (GO:0009952), GABAergic neuron differentiation in basal ganglia (GO:0021858), multicellular organism growth (GO:0035264), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of neurogenesis (GO:0050767), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), gene expression (GO:0010467), GABAergic neuron differentiation (GO:0097154)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), identical protein binding (GO:0042802), protein dimerization activity (GO:0046983), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
transcription by RNA polymerase II3
regulation of transcription by RNA polymerase II3
RNA polymerase II transcription regulatory region sequence-specific DNA binding3
regulation of DNA-templated transcription2
DNA-templated transcription2
multicellular organismal process2
protein binding2
feeding behavior1
nervous system development1
system development1
multicellular organism development1
regionalization1
GABAergic neuron differentiation1
developmental growth1
positive regulation of DNA-templated transcription1
neurogenesis1
regulation of nervous system development1
regulation of cell development1
negative regulation of DNA-templated transcription1
regulation of gene expression1
regulation of RNA biosynthetic process1
macromolecule biosynthetic process1
neuron differentiation1
cis-regulatory region sequence-specific DNA binding1
chromatin1
DNA-binding transcription factor activity1
negative regulation of transcription by RNA polymerase II1
DNA-binding transcription factor activity, RNA polymerase II-specific1
DNA-binding transcription repressor activity1
nucleic acid binding1
transcription cis-regulatory region binding1
transcription regulator activity1
binding1
chromosome1
cellular anatomical structure1
intracellular membrane-bounded organelle1
protein-containing complex1

Protein interactions and networks

STRING

478 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
HELTSLC6A7Q99884801
HELTASCL1P50553624
HELTTAL2Q16559504
HELTWDR83OSQ9Y284473
HELTING2Q9H160427
HELTHES3Q5TGS1396
HELTSNX25Q9H3E2391
HELTSLC25A4P12235371
HELTSOX14O95416354
HELTOVOL1O14753353
HELTGATMP50440353
HELTSORBS2O94875344
HELTMLXQ9UH92342
HELTPDLIM3Q53GG5328
HELTMNTQ99583321

IntAct

2 interactions, top by confidence:

ABTypeScore
HELTSORT1psi-mi:“MI:0915”(physical association)0.400

BioGRID (12): HELT (Two-hybrid), HELT (Two-hybrid), HELT (Two-hybrid), HELT (Two-hybrid), HELT (Two-hybrid), HELT (Two-hybrid), HELT (Two-hybrid), MAGEA12 (Two-hybrid), GPSM3 (Two-hybrid), HELT (Affinity Capture-MS), SORT1 (Affinity Capture-MS), HELT (Affinity Capture-MS)

ESM2 similar proteins: A4D2P6, A5PJV8, A6NFD8, D4AE48, O00268, O00287, O35274, O35779, O43566, P04198, P12755, P55199, Q08DA0, Q0D2I5, Q2KJ58, Q504T8, Q5XKK7, Q60698, Q61976, Q6NZ67, Q6P582, Q6R891, Q6T4P5, Q7Z6J2, Q80YR4, Q86UD0, Q86UK7, Q8BXL9, Q8CEG5, Q8R4T5, Q8TF61, Q8VCG9, Q969F2, Q969G9, Q96HZ4, Q96SB3, Q99PV5, Q9BQ61, Q9BUN5, Q9BZE9

Diamond homologs: A0MLS5, A6NFD8, O00327, O02219, O02748, O08785, O15516, O15945, O61734, O88529, P27540, P41739, P53762, P79832, P90953, P97460, Q2NL18, Q2VPD4, Q5R4T2, Q5RAK8, Q5ZQU2, Q61324, Q6YGZ4, Q6YGZ5, Q78E60, Q7TS99, Q8BGD7, Q8IUM7, Q8QGQ6, Q8QGQ7, Q8WYA1, Q91YA8, Q91YA9, Q91YB0, Q91YB2, Q99743, Q9BE97, Q9DBX7, Q9DG12, Q9EPW1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance66
Likely benign2
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

433 predictions. Top by Δscore:

VariantEffectΔscore
4:185018951:GCAAA:Gdonor_gain1.0000
4:185018956:G:GGdonor_gain1.0000
4:185019045:G:GTdonor_gain1.0000
4:185019386:GA:Gacceptor_gain1.0000
4:185019386:GAGA:Gacceptor_gain1.0000
4:185019832:G:Tdonor_gain1.0000
4:185020271:A:AGacceptor_gain1.0000
4:185020272:G:GTacceptor_gain1.0000
4:185020272:GC:Gacceptor_gain1.0000
4:185020272:GCA:Gacceptor_gain1.0000
4:185020272:GCAGA:Gacceptor_gain1.0000
4:185018948:A:Tdonor_gain0.9900
4:185018952:CAAAG:Cdonor_loss0.9900
4:185018953:AAAG:Adonor_loss0.9900
4:185018954:AA:Adonor_gain0.9900
4:185018954:AAGTG:Adonor_loss0.9900
4:185018955:AG:Adonor_loss0.9900
4:185018956:G:Cdonor_loss0.9900
4:185018957:TGA:Tdonor_loss0.9900
4:185018958:GAG:Gdonor_loss0.9900
4:185018994:G:GAdonor_gain0.9900
4:185019060:GACTT:Gdonor_gain0.9900
4:185019381:TCGCA:Tacceptor_loss0.9900
4:185019382:CGCA:Cacceptor_loss0.9900
4:185019384:CA:Cacceptor_loss0.9900
4:185019385:A:AGacceptor_gain0.9900
4:185019385:A:Gacceptor_loss0.9900
4:185019386:G:GGacceptor_gain0.9900
4:185019386:G:GTacceptor_loss0.9900
4:185019386:GAGAA:Gacceptor_gain0.9900

AlphaMissense

1570 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
4:185019414:G:AE19K1.000
4:185019415:A:TE19V1.000
4:185019416:A:CE19D1.000
4:185019416:A:TE19D1.000
4:185019417:A:GK20E1.000
4:185019419:G:CK20N1.000
4:185019419:G:TK20N1.000
4:185019421:G:CR21P1.000
4:185019423:A:GR22G1.000
4:185019423:A:TR22W1.000
4:185019424:G:CR22T1.000
4:185019424:G:TR22M1.000
4:185019425:G:CR22S1.000
4:185019425:G:TR22S1.000
4:185019426:A:TR23W1.000
4:185019427:G:CR23T1.000
4:185019427:G:TR23M1.000
4:185019428:G:CR23S1.000
4:185019428:G:TR23S1.000
4:185019433:G:TR25M1.000
4:185019434:G:CR25S1.000
4:185019434:G:TR25S1.000
4:185019436:T:AI26N1.000
4:185019436:T:CI26T1.000
4:185019436:T:GI26S1.000
4:185019438:A:GN27D1.000
4:185019440:C:AN27K1.000
4:185019440:C:GN27K1.000
4:185019444:T:CC29R1.000
4:185019448:T:CL30S1.000

dbSNP variants (sampled 300 via entrez): RS1000423070 (4:185017863 A>C), RS1002412120 (4:185018225 A>C), RS1002729140 (4:185018198 C>T), RS1002784837 (4:185018466 C>A,T), RS1003515852 (4:185021174 G>A), RS1003610902 (4:185021352 G>C), RS1004191025 (4:185019639 G>A,T), RS1004467678 (4:185019882 G>A,C,T), RS1004668764 (4:185017022 G>A), RS1005506590 (4:185020244 C>G), RS1006140277 (4:185018483 G>T), RS1007042533 (4:185021431 A>C), RS1007479824 (4:185019290 C>T), RS1008478037 (4:185017838 C>G,T), RS1008805170 (4:185017336 A>G)

Disease associations

OMIM: gene MIM:617546 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST003542_35Night sleep phenotypes6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

ChemicalActions (top 5)PubMed papers
Cadmiumincreases abundance, increases expression, decreases expression2
bisphenol Aaffects cotreatment, increases methylation1
arseniteincreases methylation1
CGP 52608increases reaction, affects binding1
Resveratrolaffects cotreatment, decreases expression1
Fulvestrantaffects cotreatment, increases methylation1
Benzo(a)pyreneaffects methylation, increases methylation1
Plant Extractsaffects cotreatment, decreases expression1
Cadmium Chloridedecreases expression, increases abundance1

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

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