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

    Gene ID: 4808, updated on 2-Nov-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. Implicated in hypogonadotropic hypogonadism. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
    mouse all
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    Genomic context

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    See NHLH2 in Genome Data Viewer
    Location:
    1p13.1
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (115831344..115841126, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (115837717..115849134, complement)
    RS_2024_09 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 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. Inactivating NHLH2 variants cause idiopathic hypogonadotropic hypogonadism and obesity in humans. Topaloglu AK, et al. Hum Genet, 2022 Feb. PMID 35066646
    2. 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
    3. 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
    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. LMO3 interacts with neuronal transcription factor, HEN2, and acts as an oncogene in neuroblastoma. Aoyama M, et al. Cancer Res, 2005 Jun 1. PMID 15930276

    See all (27) 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
    located_in 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_2024_08

    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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