U.S. flag

An official website of the United States government

ERBB4 erb-b2 receptor tyrosine kinase 4 [ Homo sapiens (human) ]

Gene ID: 2066, updated on 4-Jan-2025

Summary

Official Symbol
ERBB4provided by HGNC
Official Full Name
erb-b2 receptor tyrosine kinase 4provided by HGNC
Primary source
HGNC:HGNC:3432
See related
Ensembl:ENSG00000178568 MIM:600543; AllianceGenome:HGNC:3432
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
HER4; ALS19; p180erbB4
Summary
This gene is a member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. It encodes a single-pass type I membrane protein with multiple cysteine rich domains, a transmembrane domain, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins and other factors and induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]
Expression
Biased expression in kidney (RPKM 3.0), brain (RPKM 2.7) and 8 other tissues See more
Orthologs
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

See ERBB4 in Genome Data Viewer
Location:
2q34
Exon count:
31
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (211375717..212538802, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (211856201..213019445, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (212240442..213403526, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene 5'-nucleotidase domain containing 2 pseudogene Neighboring gene NANOG hESC enhancer GRCh37_chr2:211994958-211995459 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:212092893-212093684 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:212093685-212094476 Neighboring gene VISTA enhancer hs1578 Neighboring gene ribosomal protein S27 pseudogene 10 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:212278303-212278804 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:212278805-212279304 Neighboring gene NANOG hESC enhancer GRCh37_chr2:212363277-212363781 Neighboring gene RNA, 5S ribosomal pseudogene 119 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:212631258-212631794 Neighboring gene MT-ND2 pseudogene 23 Neighboring gene MT-CO1 pseudogene 46 Neighboring gene uncharacterized LOC124906116 Neighboring gene NANOG hESC enhancer GRCh37_chr2:213291716-213292249 Neighboring gene microRNA 548f-2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:213402057-213402557 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17056 Neighboring gene long intergenic non-protein coding RNA 1878 Neighboring gene PC-esterase domain containing 1C, pseudogene

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2024-10-23)

ClinGen Genome Curation Page
Haploinsufficency

Little evidence for dosage pathogenicity (Last evaluated 2024-10-23)

ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study.
EBI GWAS Catalog
Genetics of coronary artery calcification among African Americans, a meta-analysis.
EBI GWAS Catalog
Genome-wide association studies and heritability estimates of body mass index related phenotypes in bangladeshi adults.
EBI GWAS Catalog
Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.
EBI GWAS Catalog
Genome-wide association study of the five-factor model of personality in young Korean women.
EBI GWAS Catalog
Genome-wide association study on dimethylarginines reveals novel AGXT2 variants associated with heart rate variability but not with overall mortality.
EBI GWAS Catalog
Genome-wide interaction studies reveal sex-specific asthma risk alleles.
EBI GWAS Catalog
New susceptibility loci associated with kidney disease in type 1 diabetes.
EBI GWAS Catalog

Pathways from PubChem

Interactions

General gene information

Clone Names

  • MGC138404

Gene Ontology Provided by GOA

Items 1 - 25 of 29
Function Evidence Code Pubs
enables ATP binding  
enables GABA receptor binding  
enables GPI-linked ephrin receptor activity  
enables boss receptor activity  
enables brain-derived neurotrophic factor receptor activity  
enables epidermal growth factor receptor activity  
enables epidermal growth factor receptor binding  
enables epidermal growth factor receptor binding PubMed 
enables fibroblast growth factor receptor activity  
enables hepatocyte growth factor receptor activity  
enables histone H2AXY142 kinase activity  
enables histone H3Y41 kinase activity  
enables insulin receptor activity  
enables insulin-like growth factor receptor activity  
enables macrophage colony-stimulating factor receptor activity  
enables neuregulin receptor activity PubMed 
enables placental growth factor receptor activity  
enables platelet-derived growth factor alpha-receptor activity  
enables platelet-derived growth factor beta-receptor activity  
enables protein binding PubMed 
enables protein homodimerization activity PubMed 
enables protein tyrosine kinase activity PubMed 
enables protein tyrosine kinase collagen receptor activity  
enables stem cell factor receptor activity  
enables transcription cis-regulatory region binding PubMed 
enables transmembrane receptor protein tyrosine kinase activity  
enables transmembrane receptor protein tyrosine kinase activity PubMed 
enables transmembrane-ephrin receptor activity  
enables vascular endothelial growth factor receptor activity  
Items 1 - 25 of 29
Items 1 - 25 of 58
Process Evidence Code Pubs
involved_in ERBB2-ERBB4 signaling pathway  
involved_in ERBB4 signaling pathway PubMed 
involved_in ERBB4-ERBB4 signaling pathway PubMed 
involved_in Kit signaling pathway  
involved_in brain-derived neurotrophic factor receptor signaling pathway  
involved_in cardiac muscle tissue regeneration  
involved_in cell fate commitment  
involved_in cell migration PubMed 
involved_in cell surface receptor protein tyrosine kinase signaling pathway  
involved_in cell surface receptor protein tyrosine kinase signaling pathway PubMed 
involved_in cell surface receptor signaling pathway via JAK-STAT  
involved_in cellular response to epidermal growth factor stimulus  
involved_in central nervous system morphogenesis  
involved_in chromatin remodeling  
involved_in collagen-activated tyrosine kinase receptor signaling pathway  
involved_in embryonic pattern specification  
involved_in ephrin receptor signaling pathway  
involved_in epidermal growth factor receptor signaling pathway  
involved_in establishment of planar polarity involved in nephron morphogenesis  
involved_in fibroblast growth factor receptor signaling pathway  
involved_in heart development  
involved_in hepatocyte growth factor receptor signaling pathway  
involved_in insulin receptor signaling pathway  
involved_in insulin-like growth factor receptor signaling pathway  
involved_in lactation PubMed 
involved_in macrophage colony-stimulating factor signaling pathway  
involved_in mammary gland alveolus development  
involved_in mammary gland epithelial cell differentiation  
involved_in mitochondrial fragmentation involved in apoptotic process PubMed 
involved_in multicellular organism development  
involved_in negative regulation of apoptotic process  
involved_in negative regulation of apoptotic process PubMed 
involved_in negative regulation of cell population proliferation PubMed 
involved_in negative regulation of neuron migration  
involved_in nervous system development  
involved_in neural crest cell migration  
involved_in neurogenesis  
involved_in neurotransmitter receptor localization to postsynaptic specialization membrane  
involved_in olfactory bulb interneuron differentiation  
involved_in peptidyl-tyrosine phosphorylation PubMed 
involved_in platelet-derived growth factor receptor-alpha signaling pathway  
involved_in platelet-derived growth factor receptor-beta signaling pathway  
involved_in positive regulation of DNA-templated transcription PubMed 
involved_in positive regulation of ERK1 and ERK2 cascade PubMed 
involved_in positive regulation of cardiac muscle cell proliferation  
involved_in positive regulation of cell population proliferation  
involved_in positive regulation of cell population proliferation PubMed 
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction  
involved_in positive regulation of protein localization to cell surface  
involved_in positive regulation of protein phosphorylation PubMed 
involved_in positive regulation of receptor signaling pathway via JAK-STAT PubMed 
involved_in positive regulation of tyrosine phosphorylation of STAT protein PubMed 
involved_in protein autophosphorylation PubMed 
involved_in regulation of cell migration  
involved_in signal transduction PubMed 
involved_in synapse assembly  
involved_in vascular endothelial growth factor receptor-1 signaling pathway  
involved_in vascular endothelial growth factor signaling pathway  
Items 1 - 25 of 58
Component Evidence Code Pubs
located_in GABA-ergic synapse  
is_active_in basal plasma membrane  
located_in basolateral plasma membrane PubMed 
located_in cytosol  
located_in extracellular region  
located_in glutamatergic synapse  
located_in mitochondrial matrix  
located_in mitochondrion PubMed 
located_in neuromuscular junction  
located_in nucleoplasm  
located_in nucleus PubMed 
is_active_in plasma membrane  
is_active_in plasma membrane PubMed 
located_in plasma membrane  
located_in postsynaptic density membrane  
located_in postsynaptic membrane  
located_in presynaptic membrane  
part_of receptor complex  
part_of receptor complex PubMed 

General protein information

Preferred Names
receptor tyrosine-protein kinase erbB-4
Names
avian erythroblastic leukemia viral (v-erb-b2) oncogene homolog 4
human epidermal growth factor receptor 4
proto-oncogene-like protein c-ErbB-4
tyrosine kinase-type cell surface receptor HER4
v-erb-a erythroblastic leukemia viral oncogene homolog 4
v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4
NP_001036064.1
NP_005226.1
XP_005246433.1
XP_005246434.1
XP_006712427.1
XP_016859066.1
XP_016859067.1
XP_016859068.1
XP_016859069.1
XP_016859070.1
XP_016859071.1
XP_054196992.1
XP_054196993.1
XP_054196994.1
XP_054196995.1
XP_054196996.1
XP_054196997.1
XP_054196998.1
XP_054196999.1
XP_054197000.1

NCBI Reference Sequences (RefSeq)

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_011805.2 RefSeqGene

    Range
    4827..1167912
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001042599.1NP_001036064.1  receptor tyrosine-protein kinase erbB-4 isoform JM-a/CVT-2 precursor

    See identical proteins and their annotated locations for NP_001036064.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (JM-a/CYT-2) lacks an alternate in-frame exon, compared to variant JM-a/CYT-1, resulting in a shorter protein (isoform JM-a/CYT-2) that lacks the phosphotidylinositol-3 kinase binding site, compared to isoform JM-a/CYT-1.
    Source sequence(s)
    AB209697, AC012069, AI793060, BC112199, BQ015804, L07868
    Consensus CDS
    CCDS42811.1
    Related
    ENSP00000403204.1, ENST00000436443.5
    Conserved Domains (5) summary
    cd05110
    Location:7101012
    PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4
    cd12092
    Location:642685
    TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase
    pfam00757
    Location:186332
    Furin-like; Furin-like cysteine rich region
    pfam01030
    Location:55167
    Recep_L_domain; Receptor L domain
    pfam14843
    Location:502634
    GF_recep_IV; Growth factor receptor domain IV
  2. NM_005235.3NP_005226.1  receptor tyrosine-protein kinase erbB-4 isoform JM-a/CVT-1 precursor

    See identical proteins and their annotated locations for NP_005226.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (JM-a/CYT-1) represents the longer transcript and encodes the longer isoform (JM-a/CYT-1).
    Source sequence(s)
    AC012069, AC096765, AI793060, BQ015804, CR627023, L07868
    Consensus CDS
    CCDS2394.1
    UniProtKB/Swiss-Prot
    B7ZLD7, B7ZLE2, B7ZLE3, Q15303, Q2M1W1, Q59EW4
    Related
    ENSP00000342235.4, ENST00000342788.9
    Conserved Domains (5) summary
    cd05110
    Location:7101012
    PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4
    cd12092
    Location:642685
    TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase
    pfam00757
    Location:186332
    Furin-like; Furin-like cysteine rich region
    pfam01030
    Location:55167
    Recep_L_domain; Receptor L domain
    pfam14843
    Location:502634
    GF_recep_IV; Growth factor receptor domain IV

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_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    211375717..212538802 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005246377.4XP_005246434.1  receptor tyrosine-protein kinase erbB-4 isoform X8

    See identical proteins and their annotated locations for XP_005246434.1

    Related
    ENSP00000260943.7, ENST00000260943.11
    Conserved Domains (5) summary
    cd05110
    Location:7001002
    PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4
    cd12092
    Location:632675
    TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase
    pfam00757
    Location:186332
    Furin-like; Furin-like cysteine rich region
    pfam01030
    Location:55167
    Recep_L_domain; Receptor L domain
    pfam14843
    Location:502634
    GF_recep_IV; Growth factor receptor domain IV
  2. XM_005246376.4XP_005246433.1  receptor tyrosine-protein kinase erbB-4 isoform X7

    See identical proteins and their annotated locations for XP_005246433.1

    Conserved Domains (5) summary
    cd05110
    Location:7001002
    PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4
    cd12092
    Location:632675
    TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase
    pfam00757
    Location:186332
    Furin-like; Furin-like cysteine rich region
    pfam01030
    Location:55167
    Recep_L_domain; Receptor L domain
    pfam14843
    Location:502634
    GF_recep_IV; Growth factor receptor domain IV
  3. XM_006712364.4XP_006712427.1  receptor tyrosine-protein kinase erbB-4 isoform X5

    Conserved Domains (8) summary
    cd05110
    Location:7251027
    PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4
    cd12092
    Location:657700
    TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase
    smart00261
    Location:549596
    FU; Furin-like repeats
    cd00064
    Location:229274
    FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.
    pfam00757
    Location:186332
    Furin-like; Furin-like cysteine rich region
    pfam01030
    Location:55167
    Recep_L_domain; Receptor L domain
    pfam07714
    Location:733989
    Pkinase_Tyr; Protein tyrosine kinase
    pfam14843
    Location:502634
    GF_recep_IV; Growth factor receptor domain IV
  4. XM_017003581.3XP_016859070.1  receptor tyrosine-protein kinase erbB-4 isoform X6

  5. XM_017003578.3XP_016859067.1  receptor tyrosine-protein kinase erbB-4 isoform X2

  6. XM_017003580.3XP_016859069.1  receptor tyrosine-protein kinase erbB-4 isoform X4

  7. XM_017003579.3XP_016859068.1  receptor tyrosine-protein kinase erbB-4 isoform X3

  8. XM_017003577.3XP_016859066.1  receptor tyrosine-protein kinase erbB-4 isoform X1

  9. XM_017003582.2XP_016859071.1  receptor tyrosine-protein kinase erbB-4 isoform X9

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    211856201..213019445 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054341024.1XP_054196999.1  receptor tyrosine-protein kinase erbB-4 isoform X8

  2. XM_054341023.1XP_054196998.1  receptor tyrosine-protein kinase erbB-4 isoform X7

  3. XM_054341021.1XP_054196996.1  receptor tyrosine-protein kinase erbB-4 isoform X5

  4. XM_054341022.1XP_054196997.1  receptor tyrosine-protein kinase erbB-4 isoform X6

  5. XM_054341018.1XP_054196993.1  receptor tyrosine-protein kinase erbB-4 isoform X2

  6. XM_054341020.1XP_054196995.1  receptor tyrosine-protein kinase erbB-4 isoform X4

  7. XM_054341019.1XP_054196994.1  receptor tyrosine-protein kinase erbB-4 isoform X3

  8. XM_054341017.1XP_054196992.1  receptor tyrosine-protein kinase erbB-4 isoform X1

  9. XM_054341025.1XP_054197000.1  receptor tyrosine-protein kinase erbB-4 isoform X9

External link. Please review our privacy policy.