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... See more...

Aliases for HAND1 Gene

Aliases for HAND1 Gene

  • Heart And Neural Crest Derivatives Expressed 1 2 3 5
  • Extraembryonic Tissues, Heart, Autonomic Nervous System And Neural Crest Derivatives-Expressed Protein 1 3 4
  • Heart- And Neural Crest Derivatives-Expressed Protein 1 3 4
  • Class A Basic Helix-Loop-Helix Protein 27 3 4
  • BHLHa27 3 4
  • EHAND 4 4
  • BHLHA27 4
  • Thing1 3
  • EHand 3
  • Hxt 3

External Ids for HAND1 Gene

Previous GeneCards Identifiers for HAND1 Gene

  • GC05M153925
  • GC05M153883
  • GC05M153834
  • GC05M148995

Summaries for HAND1 Gene

Entrez Gene Summary for HAND1 Gene

  • 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, it has been suggested that this transcription factor may be required for early trophoblast differentiation. [provided by RefSeq, Jul 2008]

GeneCards Summary for HAND1 Gene

HAND1 (Heart And Neural Crest Derivatives Expressed 1) is a Protein Coding gene. Diseases associated with HAND1 include Hypoplastic Left Heart Syndrome and Hypoplastic Left Heart Syndrome 1. Among its related pathways are Heart Development and Signaling pathways regulating pluripotency of stem cells. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and identical protein binding. An important paralog of this gene is HAND2.

UniProtKB/Swiss-Prot Summary for HAND1 Gene

  • Transcription factor that plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis. In the adult, could be required for ongoing expression of cardiac-specific genes. Binds the DNA sequence 5'-NRTCTG-3' (non-canonical E-box) (By similarity).

Gene Wiki entry for HAND1 Gene

Additional gene information for HAND1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HAND1 Gene

Genomics for HAND1 Gene

GeneHancer (GH) Regulatory Elements for HAND1 Gene

Promoters and enhancers for HAND1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH05J154476 Promoter/Enhancer 1.6 EPDnew FANTOM5 Ensembl ENCODE 515.2 +1.0 963 3.8 ZIC2 SAP30 EZH2 HDAC2 MXI1 KLF9 SP2 YY1 TCF12 ZFHX2 HAND1 SAP30L NONHSAG042005.2 RF00017-5020
GH05J154583 Enhancer 1 FANTOM5 ENCODE 17.6 -106.4 -106378 2 ZNF217 TCF12 ZIC2 EP300 GATAD2B CTBP1 DEK MYC SMARCC1 MBD2 HAND1 MRPL22 SAP30L MIR3141 CIR1P1 RF00017-5020
GH05J154522 Enhancer 1.1 FANTOM5 Ensembl ENCODE 14.3 -45.8 -45806 2.9 JUND ZIC2 ZNF423 TRIM28 REST ATF2 MXI1 RBM25 ZBTB17 GATA3 HAND1 LOC100271907 lnc-HAND1-4 RF00017-5020
GH05J154520 Enhancer 1.1 Ensembl ENCODE CraniofacialAtlas 11.6 -43.1 -43141 1.7 CTCF TEAD4 ZNF423 EP300 TRIM22 TEAD1 HDAC2 DEK RAD21 YY1 HAND1 LOC100271907 lnc-HAND1-4 RF00017-5020
GH05J154405 Promoter/Enhancer 1.2 ENCODE CraniofacialAtlas 10.3 +72.9 72904 0.6 RXRA CTCF MYC ZNF10 ZIC2 ZNF423 GABPA ZBTB26 TARDBP REST GALNT10 HAND1 RF00017-5022 lnc-HAND1-5 SAP30L-AS1 lnc-SAP30L-3 RF00017-5021 RN7SL655P RF00017-5020
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HAND1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HAND1

Top Transcription factor binding sites by QIAGEN in the HAND1 gene promoter:
  • AREB6
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • RelA

Genomic Locations for HAND1 Gene

Genomic Locations for HAND1 Gene
chr5:154,474,972-154,478,264
(GRCh38/hg38)
Size:
3,293 bases
Orientation:
Minus strand
chr5:153,854,532-153,857,824
(GRCh37/hg19)
Size:
3,293 bases
Orientation:
Minus strand

Genomic View for HAND1 Gene

Genes around HAND1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HAND1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HAND1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HAND1 Gene

Proteins for HAND1 Gene

  • Protein details for HAND1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O96004-HAND1_HUMAN
    Recommended name:
    Heart- and neural crest derivatives-expressed protein 1
    Protein Accession:
    O96004

    Protein attributes for HAND1 Gene

    Size:
    215 amino acids
    Molecular mass:
    23627 Da
    Quaternary structure:
    • Efficient DNA binding requires dimerization with another bHLH protein. Forms homodimers and heterodimers with TCF3 gene products E12 and E47, HAND2 and HEY1, HEY2 and HEYL (hairy-related transcription factors). Interacts with MDFIC (By similarity).

neXtProt entry for HAND1 Gene

Post-translational modifications for HAND1 Gene

  • Phosphorylation by PLK4 disrupts the interaction with MDFIC and leads to translocation into the nucleoplasm, allowing dimerization and transcription factor activity.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for HAND1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for HAND1 Gene

Domains & Families for HAND1 Gene

Gene Families for HAND1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for HAND1 Gene

Blocks:
  • Basic helix-loop-helix dimerization domain bHLH
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for HAND1 Gene

GenScript: Design optimal peptide antigens:
  • Extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (HAND1_HUMAN)
genes like me logo Genes that share domains with HAND1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for HAND1 Gene

Function for HAND1 Gene

Molecular function for HAND1 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor that plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis. In the adult, could be required for ongoing expression of cardiac-specific genes. Binds the DNA sequence 5'-NRTCTG-3' (non-canonical E-box) (By similarity).
GENATLAS Biochemistry:
heart and neural crest derivatives expressed 1,murine eHAND gene homolog,expressed in cytotrophoblastic cells,in prenatal and adult heart,required for trophoblast giant cell differentiation,involved in cardiac looping,ventricular maturation and conotruncal development

Phenotypes From GWAS Catalog for HAND1 Gene

Gene Ontology (GO) - Molecular Function for HAND1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 11802795
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific IDA,NAS 19274049
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific IDA 11802795
GO:0003677 DNA binding IEA --
GO:0003713 transcription coactivator activity IEA --
genes like me logo Genes that share ontologies with HAND1: view
genes like me logo Genes that share phenotypes with HAND1: view

Animal Models for HAND1 Gene

MGI Knock Outs for HAND1:

Animal Model Products

CRISPR Products

Transcription Factor Targets for HAND1 Gene

Selected GeneGlobe predicted Target genes for HAND1

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology and HOMER Transcription for HAND1 Gene

Localization for HAND1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HAND1 Gene

Nucleus, nucleoplasm. Nucleus, nucleolus. Note=Interaction with MDFIC sequesters it into the nucleolus, preventing the transcription factor activity. Phosphorylation by PLK4 disrupts the interaction with MDFIC and releases it from the nucleolus, leading to transcription factor activity (By similarity). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HAND1 gene
Compartment Confidence
nucleus 5
plasma membrane 2
extracellular 2
mitochondrion 2
cytosol 2
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear membrane (1)
  • Nucleoplasm (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for HAND1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IEA,IDA 11802795
GO:0005654 nucleoplasm IEA --
GO:0005730 nucleolus IEA --
GO:0005737 cytoplasm IDA 11802795
genes like me logo Genes that share ontologies with HAND1: view

Pathways & Interactions for HAND1 Gene

PathCards logo

SuperPathways for HAND1 Gene

SuperPathway Contained pathways
1 NFAT and Cardiac Hypertrophy
.42
.42
2 Signaling pathways regulating pluripotency of stem cells
3 Transcriptional Regulatory Network in Embryonic Stem Cell
-
4 Heart Development
5 Mesodermal Commitment Pathway
genes like me logo Genes that share pathways with HAND1: view

Pathways by source for HAND1 Gene

3 Qiagen pathways for HAND1 Gene
  • NFAT and Cardiac Hypertrophy
  • Signaling Involved in Cardiac Hypertrophy
  • Transcriptional Regulatory Network in Embryonic Stem Cell

SIGNOR curated interactions for HAND1 Gene

Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for HAND1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 11802795
GO:0001525 angiogenesis ISS,IEA --
GO:0001701 in utero embryonic development IEA --
GO:0001707 mesoderm formation IEA --
GO:0001824 blastocyst development IEP 11802795
genes like me logo Genes that share ontologies with HAND1: view

Drugs & Compounds for HAND1 Gene

No Compound Related Data Available

Transcripts for HAND1 Gene

mRNA/cDNA for HAND1 Gene

1 REFSEQ mRNAs :
2 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for HAND1 Gene

ExUns: 1a · 1b ^ 2
SP1:
SP2:

Relevant External Links for HAND1 Gene

GeneLoc Exon Structure for
HAND1

Expression for HAND1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HAND1 Gene

mRNA differential expression in normal tissues according to GTEx for HAND1 Gene

This gene is overexpressed in Colon - Sigmoid (x22.6), Heart - Left Ventricle (x10.2), Small Intestine - Terminal Ileum (x8.3), and Colon - Transverse (x5.7).

Protein differential expression in normal tissues from HIPED for HAND1 Gene

This gene is overexpressed in Ovary (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for HAND1 Gene



Protein tissue co-expression partners for HAND1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HAND1

SOURCE GeneReport for Unigene cluster for HAND1 Gene:

Hs.152531

mRNA Expression by UniProt/SwissProt for HAND1 Gene:

O96004-HAND1_HUMAN
Tissue specificity: Heart.

Evidence on tissue expression from TISSUES for HAND1 Gene

  • Heart(4.4)
  • Nervous system(4.2)
genes like me logo Genes that share expression patterns with HAND1: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for HAND1 Gene

Orthologs for HAND1 Gene

This gene was present in the common ancestor of animals.

Orthologs for HAND1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia HAND1 31 30
  • 99.22 (n)
OneToOne
dog
(Canis familiaris)
Mammalia HAND1 31
  • 96 (a)
OneToOne
cow
(Bos Taurus)
Mammalia HAND1 31 30
  • 93.33 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hand1 30
  • 87.91 (n)
mouse
(Mus musculus)
Mammalia Hand1 17 31 30
  • 86.98 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia HAND1 31
  • 84 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia HAND1 31
  • 84 (a)
OneToOne
chicken
(Gallus gallus)
Aves HAND1 31 30
  • 77.66 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 27 (a)
ManyToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia hand1 30
  • 68.05 (n)
Str.11172 30
African clawed frog
(Xenopus laevis)
Amphibia hand1-A 30
zebrafish
(Danio rerio)
Actinopterygii twist3 31
  • 21 (a)
ManyToMany
fruit fly
(Drosophila melanogaster)
Insecta Hand 31 30
  • 48.63 (n)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.4380 31
  • 18 (a)
OneToMany
Species where no ortholog for HAND1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for HAND1 Gene

ENSEMBL:
Gene Tree for HAND1 (if available)
TreeFam:
Gene Tree for HAND1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HAND1: view image

Paralogs for HAND1 Gene

(2) SIMAP similar genes for HAND1 Gene using alignment to 1 proteins:

  • HAND1_HUMAN
genes like me logo Genes that share paralogs with HAND1: view

Variants for HAND1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HAND1 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
656575 Uncertain Significance: Hypoplastic left heart syndrome 154,477,822(-) G/A MISSENSE_VARIANT
695808 Benign: not provided 154,477,847(-) C/T SYNONYMOUS_VARIANT
698415 Likely Benign: not provided 154,477,835(-) C/G SYNONYMOUS_VARIANT
rs1177737621 Uncertain Significance: Hypoplastic left heart syndrome 154,477,752(-) T/A MISSENSE_VARIANT
rs201302313 Benign/Likely Benign: not specified; not provided 154,477,762(-) C/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for HAND1 Gene

Structural Variations from Database of Genomic Variants (DGV) for HAND1 Gene

Variant ID Type Subtype PubMed ID
esv275523 CNV loss 21479260
nsv830520 CNV loss 17160897

Variation tolerance for HAND1 Gene

Residual Variation Intolerance Score: 53.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.05; 21.47% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HAND1 Gene

Human Gene Mutation Database (HGMD)
HAND1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HAND1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HAND1 Gene

Disorders for HAND1 Gene

MalaCards: The human disease database

(8) MalaCards diseases for HAND1 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
hypoplastic left heart syndrome
  • hlhs
hypoplastic left heart syndrome 1
  • hlhs1
double outlet right ventricle
  • dextrotransposition of aorta
heart disease
  • congenital heart disease
tetralogy of fallot
  • tof
- elite association - COSMIC cancer census association via MalaCards
Search HAND1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HAND1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with HAND1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HAND1 Gene

Publications for HAND1 Gene

  1. Molecular cloning of the human Hand1 gene/cDNA and its tissue-restricted expression in cytotrophoblastic cells and heart. (PMID: 9931445) Knöfler M … Egarter C (Gene 1998) 2 3 4 23 54
  2. A functional genetic study identifies HAND1 mutations in septation defects of the human heart. (PMID: 19586923) Reamon-Buettner SM … Borlak J (Human molecular genetics 2009) 3 41 54
  3. A loss-of-function mutation in the binding domain of HAND1 predicts hypoplasia of the human hearts. (PMID: 18276607) Reamon-Buettner SM … Borlak J (Human molecular genetics 2008) 3 23 54
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 54
  5. Differential regulation of Hand1 homodimer and Hand1-E12 heterodimer activity by the cofactor FHL2. (PMID: 15509787) Hill AA … Riley PR (Molecular and cellular biology 2004) 3 23 54

Products for HAND1 Gene

Sources for HAND1 Gene