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NHLH2 nescient helix-loop-helix 2 [ Homo sapiens (human) ]

Gene ID: 4808, updated on 3-Apr-2024

Summary

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Official Symbol
NHLH2provided by HGNC
Official Full Name
nescient helix-loop-helix 2provided by HGNC
Primary source
HGNC:HGNC:7818
See related
Ensembl:ENSG00000177551 MIM:162361; AllianceGenome:HGNC:7818
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HEN2; HH27; NSCL2; bHLHa34
Summary
Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within with a positive effect on apoptotic process; hypothalamus gonadotrophin-releasing hormone neuron development; and peripheral nervous system development. Predicted to act upstream of or within several processes, including cell migration in hindbrain; male gonad development; and male mating behavior. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Low expression observed in reference dataset See more
Orthologs
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Genomic context

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Location:
1p13.1
Exon count:
5
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (115831344..115841126, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (115837717..115849134, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (116378998..116383747, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:116184448-116185206 Neighboring gene Sharpr-MPRA regulatory region 4355 Neighboring gene VANGL planar cell polarity protein 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:116214007-116214561 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:116238833-116239332 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:116253505-116254147 Neighboring gene calsequestrin 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1555 Neighboring gene heterogeneous nuclear ribonucleoprotein A1 pseudogene 43 Neighboring gene NANOG hESC enhancer GRCh37_chr1:116422522-116423061 Neighboring gene serine palmitoyltransferase small subunit A-like

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. In Silico Examination of Single Nucleotide Missense Mutations in NHLH2, a Gene Linked to Infertility and Obesity. Madsen AT, et al. Int J Mol Sci, 2023 Feb 6. PMID 36834605, Free PMC Article
  2. Inactivating NHLH2 variants cause idiopathic hypogonadotropic hypogonadism and obesity in humans. Topaloglu AK, et al. Hum Genet, 2022 Feb. PMID 35066646
  3. Natural Selection at the NHLH2 Core Promoter Exceptionally Long CA-Repeat in Human and Disease-Only Genotypes in Late-Onset Neurocognitive Disorder. Afshar H, et al. Gerontology, 2020. PMID 32877896
  4. Two single nucleotide polymorphisms in the human nescient helix-loop-helix 2 (NHLH2) gene reduce mRNA stability and DNA binding. Al Rayyan N, et al. Gene, 2013 Jan 1. PMID 23026212, Free PMC Article
  5. A Genetic Basis for Motivated Exercise. Good DJ, et al. Exerc Sport Sci Rev, 2015 Oct. PMID 26196864

See all (26) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. In Silico Examination of Single Nucleotide Missense Mutations in NHLH2, a Gene Linked to Infertility and Obesity.
    Title: In Silico Examination of Single Nucleotide Missense Mutations in NHLH2, a Gene Linked to Infertility and Obesity.
  2. Inactivating NHLH2 variants cause idiopathic hypogonadotropic hypogonadism and obesity in humans.
    Title: Inactivating NHLH2 variants cause idiopathic hypogonadotropic hypogonadism and obesity in humans.
  3. Natural Selection at the NHLH2 Core Promoter Exceptionally Long CA-Repeat in Human and Disease-Only Genotypes in Late-Onset Neurocognitive Disorder.
    Title: Natural Selection at the NHLH2 Core Promoter Exceptionally Long CA-Repeat in Human and Disease-Only Genotypes in Late-Onset Neurocognitive Disorder.
  4. These data support part of our hypothesis that NHLH2 or MAO-A polymorphism is associated with sedentary behavior.
    Title: A Genetic Basis for Motivated Exercise.
  5. Leptin signaling regulates hypothalamic expression of Nhlh2 through Stat3.
    Title: Leptin signaling regulates hypothalamic expression of nescient helix-loop-helix 2 (Nhlh2) through signal transducer and activator 3 (Stat3).
  6. Two single nucleotide polymorphisms in the human nescient helix-loop-helix 2 (NHLH2) gene reduce mRNA stability or reduce helical structure in the DNA binding domain of the protein.
    Title: Two single nucleotide polymorphisms in the human nescient helix-loop-helix 2 (NHLH2) gene reduce mRNA stability and DNA binding.
  7. The present results suggest that a transcriptional complex of LMO3 and HEN2 may contribute to the genesis and malignant phenotype of neuroblastoma by inhibiting HES1 which suppresses the transactivation of Mash1.
    Title: Oncogenic LMO3 collaborates with HEN2 to enhance neuroblastoma cell growth through transactivation of Mash1.
  8. Observational study of gene-disease association. (HuGE Navigator)
    Title: Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk.
  9. proposes the novel hypothesis that transcriptional activity by Nhlh2 (NHLH2 in humans) controls either the ability or the motivation for exercise [review]
    Title: Nhlh2: a basic helix-loop-helix transcription factor controlling physical activity.
  10. The deregulated expression of neuronal-specific LMO3 and HEN2 contributes to the genesis and progression of human neuroblastoma in a lineage-specific manner.
    Title: LMO3 interacts with neuronal transcription factor, HEN2, and acts as an oncogene in neuroblastoma.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Hypogonadotropic hypogonadism 27 without anosmia
MedGen: C5676921 OMIM: 619755 GeneReviews: Not available
not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA0490

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific IEA
Inferred from Electronic Annotation
more info
  
enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
Inferred from Biological aspect of Ancestor
more info
  
enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
  
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables RNA polymerase II-specific DNA-binding transcription factor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein dimerization activity IEA
Inferred from Electronic Annotation
more info
  
enables sequence-specific double-stranded DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in cell migration in hindbrain IEA
Inferred from Electronic Annotation
more info
  
involved_in central nervous system development TAS
Traceable Author Statement
more info
 PubMed 
involved_in hypothalamus gonadotrophin-releasing hormone neuron development IEA
Inferred from Electronic Annotation
more info
  
involved_in male gonad development IEA
Inferred from Electronic Annotation
more info
  
involved_in male mating behavior IEA
Inferred from Electronic Annotation
more info
  
involved_in ovulation cycle IEA
Inferred from Electronic Annotation
more info
  
involved_in peripheral nervous system development IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of DNA-binding transcription factor activity TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of transcription by RNA polymerase II TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
part_of chromatin ISA
Inferred from Sequence Alignment
more info
  
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  
part_of transcription regulator complex TAS
Traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
helix-loop-helix protein 2
Names
HEN-2
NSCL-2
class A basic helix-loop-helix protein 34

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001111061.2 → NP_001104531.1  helix-loop-helix protein 2

    See identical proteins and their annotated locations for NP_001104531.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1.
    Source sequence(s)
    AL449264, BC096360
    Consensus CDS
    CCDS885.1
    UniProtKB/Swiss-Prot
    Q02577, Q5T1P6
    UniProtKB/TrEMBL
    B2R755
    Conserved Domains (1) summary
    cd19702
    Location:63 → 135
    bHLH_TS_HEN2; basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein 2 (HEN-2) and similar proteins

  2. NM_005599.3 → NP_005590.1  helix-loop-helix protein 2

    See identical proteins and their annotated locations for NP_005590.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript.
    Source sequence(s)
    AL449264, BC096360, DA608185
    Consensus CDS
    CCDS885.1
    UniProtKB/Swiss-Prot
    Q02577, Q5T1P6
    UniProtKB/TrEMBL
    B2R755
    Related
    ENSP00000322087.3, ENST00000320238.3
    Conserved Domains (1) summary
    cd19702
    Location:63 → 135
    bHLH_TS_HEN2; basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein 2 (HEN-2) and similar proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    115831344..115841126 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047421407.1 → XP_047277363.1  helix-loop-helix protein 2 isoform X1

    UniProtKB/Swiss-Prot
    Q02577, Q5T1P6

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    115837717..115849134 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

RNA

  1. XR_008486059.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q02577.1 GenPept UniProtKB/Swiss-Prot:Q02577

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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