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

Summary

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, Dec 2024]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

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_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Inactivating NHLH2 variants cause idiopathic hypogonadotropic hypogonadism and obesity in humans.
Title: Inactivating NHLH2 variants cause idiopathic hypogonadotropic hypogonadism and obesity in humans.
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.
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.
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).
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.
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.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk.
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.
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.

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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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-146153 (e-PCR)
- UniSTS:172554

NoName (e-PCR)
- UniSTS:482763

NoName (e-PCR)
- UniSTS:481764

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)

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
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