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HAND2 heart and neural crest derivatives expressed 2 [ Homo sapiens (human) ]

Gene ID: 9464, updated on 4-Feb-2026
Official Symbol
HAND2provided by HGNC
Official Full Name
heart and neural crest derivatives expressed 2provided by HGNC
Primary source
HGNC:HGNC:4808
See related
Ensembl:ENSG00000164107 MIM:602407; AllianceGenome:HGNC:4808
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
Hed; dHand; DHAND2; Thing2; bHLHa26
Summary
The protein encoded by this gene belongs to the basic helix-loop-helix family of transcription factors. This gene product is one of two closely related family members, the HAND proteins, which are asymmetrically expressed in the developing ventricular chambers and play an essential role in cardiac morphogenesis. Working in a complementary fashion, they function in the formation of the right ventricle and aortic arch arteries, implicating them as mediators of congenital heart disease. In addition, this transcription factor plays an important role in limb and branchial arch development. [provided by RefSeq, Jul 2008]
Expression
Biased expression in endometrium (RPKM 25.0), adrenal (RPKM 21.4) and 12 other tissues See more
Orthologs
all
Try the new Gene page
Try the new Transcripts and proteins table
See HAND2 in Genome Data Viewer
Location:
4q34.1
Exon count:
2
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (173526091..173530229, complement)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (176865882..176870021, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (174447242..174451380, complement)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene stimulator of chondrogenesis 1 Neighboring gene uncharacterized LOC101928409 Neighboring gene uncharacterized LOC124900815 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:174439311-174440510 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:174445895-174446436 Neighboring gene uncharacterized LOC124900816 Neighboring gene NANOG hESC enhancer GRCh37_chr4:174457885-174458386 Neighboring gene HAND2 antisense RNA 1 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:174529467-174530044 Neighboring gene mortality factor 4 (pseudogene)

Go to nucleotide: Graphics FASTA GenBank

  • 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

Related articles in PubMed

  1. Upregulation of Fibroblast Growth Factors Caused by Heart and Neural Crest Derivatives Expressed 2 Suppression in Endometriotic Cells: A Possible Therapeutic Target in Endometriosis. Kato N, et al. Reprod Sci, 2019 Jul. PMID 30270745
  2. No evidence of HAND2 involvement in nonsyndromic cleft lip with or without cleft palate. Martinelli M, et al. Clin Oral Investig, 2012 Apr. PMID 21431856
  3. Transcription factor HAND2 mutations in sporadic Chinese patients with congenital heart disease. Shen L, et al. Chin Med J (Engl), 2010 Jul. PMID 20819618
  4. The research on screening differentially expressed genes in Hirschsprung's disease by using Microarray. Qin KW, et al. J Pediatr Surg, 2013 Nov. PMID 24210200
  5. Requirement of heart and neural crest derivatives-expressed transcript 2 during decidualization of human endometrial stromal cells in vitro. Shindoh H, et al. Fertil Steril, 2014 Jun. PMID 24745730

See all (68) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. HAND2 suppresses favipiravir efficacy in treatment of Borna disease virus infection.
    Title: HAND2 suppresses favipiravir efficacy in treatment of Borna disease virus infection.
  2. Molecular Genetic Study on HAND2 Gene Promoter in Ventricular Septal Defect.
    Title: Molecular Genetic Study on HAND2 Gene Promoter in Ventricular Septal Defect.
  3. [Association of ventricular septal defect with rare variations of the HAND2 gene].
    Title: [Association of ventricular septal defect with rare variations of the HAND2 gene].
  4. HAND2 Assists MYCN Enhancer Invasion to Regulate a Noradrenergic Neuroblastoma Phenotype.
    Title: HAND2 Assists MYCN Enhancer Invasion to Regulate a Noradrenergic Neuroblastoma Phenotype.
  5. NONO enhances mRNA processing of super-enhancer-associated GATA2 and HAND2 genes in neuroblastoma.
    Title: NONO enhances mRNA processing of super-enhancer-associated GATA2 and HAND2 genes in neuroblastoma.
  6. Genetic evaluation of HAND2 gene and its effects on thalidomide embryopathy.
    Title: Genetic evaluation of HAND2 gene and its effects on thalidomide embryopathy.
  7. Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma.
    Title: Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma.
  8. HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signalling.
    Title: HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signalling.
  9. Expression dynamics of HAND1/2 in in vitro human cardiomyocyte differentiation.
    Title: Expression dynamics of HAND1/2 in in vitro human cardiomyocyte differentiation.
  10. Haploinsufficiency of the basic helix-loop-helix transcription factor HAND2 causes congenital heart defects.
    Title: Haploinsufficiency of the basic helix-loop-helix transcription factor HAND2 causes congenital heart defects.
Submit: New GeneRIF Correction See all GeneRIFs (38)

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

Review eQTL and phenotype association data in this region using PheGenI

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ16260, MGC125303, MGC125304

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables DNA-binding transcription activator activity, RNA polymerase II-specific IDA
Inferred from Direct Assay
more info
 PubMed 
enables DNA-binding transcription activator activity, RNA polymerase II-specific IEA
Inferred from Electronic Annotation
more info
  
enables DNA-binding transcription activator activity, RNA polymerase II-specific ISS
Inferred from Sequence or Structural Similarity
more info
  
enables DNA-binding transcription factor activity 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 IEA
Inferred from Electronic Annotation
more info
  
enables DNA-binding transcription factor activity, RNA polymerase II-specific ISS
Inferred from Sequence or Structural Similarity
more info
  
enables E-box binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables E-box binding IEA
Inferred from Electronic Annotation
more info
  
contributes_to E-box binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables RNA polymerase II-specific DNA-binding transcription factor binding IEA
Inferred from Electronic Annotation
more info
  
enables RNA polymerase II-specific DNA-binding transcription factor binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables minor groove of adenine-thymine-rich DNA binding IDA
Inferred from Direct Assay
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 protein homodimerization activity IEA
Inferred from Electronic Annotation
more info
  
enables sequence-specific DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables sequence-specific double-stranded DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
contributes_to transcription cis-regulatory region binding IEA
Inferred from Electronic Annotation
more info
  
contributes_to transcription cis-regulatory region binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables transcription coactivator binding IEA
Inferred from Electronic Annotation
more info
  
enables transcription coactivator binding ISS
Inferred from Sequence or Structural Similarity
more info
  
Process Evidence Code Pubs
involved_in adult heart development IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in angiogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in cardiac neural crest cell development involved in outflow tract morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in cardiac neural crest cell development involved in outflow tract morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cardiac right ventricle formation IEA
Inferred from Electronic Annotation
more info
  
involved_in cell differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to retinoic acid IEA
Inferred from Electronic Annotation
more info
  
involved_in embryonic skeletal system development IEA
Inferred from Electronic Annotation
more info
  
involved_in heart development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in heart development IEA
Inferred from Electronic Annotation
more info
  
involved_in heart development NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in negative regulation of cardiac muscle cell apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of cardiac muscle cell apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in noradrenergic neuron differentiation NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in outflow tract morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in outflow tract morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of ERK1 and ERK2 cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of cardiac muscle hypertrophy IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of cardiac muscle hypertrophy IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in positive regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of p38MAPK cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of semaphorin-plexin signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of semaphorin-plexin signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of secondary heart field cardioblast proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of secondary heart field cardioblast proliferation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of tissue remodeling IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in thymus development IEA
Inferred from Electronic Annotation
more info
  
involved_in thymus development ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
located_in chromatin IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of transcription regulator complex IEA
Inferred from Electronic Annotation
more info
  
part_of transcription regulator complex ISS
Inferred from Sequence or Structural Similarity
more info
  
Preferred Names
heart- and neural crest derivatives-expressed protein 2
Names
basic helix-loop-helix transcription factor HAND2
class A basic helix-loop-helix protein 26
deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2

NEW Try the new Transcript table

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.

Genomic

  1. NG_046954.1 RefSeqGene

    Range
    4999..9137
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_021973.3 → NP_068808.1  heart- and neural crest derivatives-expressed protein 2

    See identical proteins and their annotated locations for NP_068808.1

    Status: REVIEWED

    Source sequence(s)
    AC093849
    Consensus CDS
    CCDS3819.1
    UniProtKB/Swiss-Prot
    B6ECG9, O95300, O95301, P61296, P97833, Q494T1
    Related
    ENSP00000352565.4, ENST00000359562.4
    Conserved Domains (1) summary
    cd11471
    Location:100 → 161
    bHLH_TS_HAND2; basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 2 (HAND2) and similar proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    173526091..173530229 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    176865882..176870021 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P61296.1 GenPept UniProtKB/Swiss-Prot:P61296

Gene LinkOut

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

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