ERBB4
erb-b2 receptor tyrosine kinase 4 | ALS19, HER4

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]

Member of: DE-4 DE-4.9 Developmental clusters: GC6
Biological processes 104 terms
ATP binding (GO:0005524)ERBB2-ERBB4 signaling pathway (GO:0038135)ERBB4 signaling pathway (GO:0038130)ERBB4 signaling pathway (GO:0038130)ERBB4 signaling pathway (GO:0038130)ERBB4-ERBB4 signaling pathway (GO:0038138)ERBB4-ERBB4 signaling pathway (GO:0038138)ERBB4-ERBB4 signaling pathway (GO:0038138)GABA receptor binding (GO:0050811)GABA-ergic synapse (GO:0098982)basal plasma membrane (GO:0009925)basolateral plasma membrane (GO:0016323)basolateral plasma membrane (GO:0016323)cardiac muscle tissue regeneration (GO:0061026)cardiac muscle tissue regeneration (GO:0061026)cell migration (GO:0016477)cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169)cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169)cell surface receptor signaling pathway (GO:0007166)cell surface receptor signaling pathway via JAK-STAT (GO:0007259)central nervous system morphogenesis (GO:0021551)central nervous system morphogenesis (GO:0021551)cytosol (GO:0005829)embryonic pattern specification (GO:0009880)embryonic pattern specification (GO:0009880)epidermal growth factor receptor activity (GO:0005006)epidermal growth factor receptor binding (GO:0005154)epidermal growth factor receptor binding (GO:0005154)epidermal growth factor receptor signaling pathway (GO:0007173)extracellular region (GO:0005576)glutamatergic synapse (GO:0098978)heart development (GO:0007507)lactation (GO:0007595)lactation (GO:0007595)mammary gland alveolus development (GO:0060749)mammary gland alveolus development (GO:0060749)mammary gland development (GO:0030879)mammary gland epithelial cell differentiation (GO:0060644)mammary gland epithelial cell differentiation (GO:0060644)membrane (GO:0016020)mitochondrial fragmentation involved in apoptotic process (GO:0043653)mitochondrial matrix (GO:0005759)mitochondrion (GO:0005739)mitochondrion (GO:0005739)negative regulation of apoptotic process (GO:0043066)negative regulation of apoptotic process (GO:0043066)negative regulation of apoptotic process (GO:0043066)negative regulation of cell population proliferation (GO:0008285)nervous system development (GO:0007399)neural crest cell migration (GO:0001755)neural crest cell migration (GO:0001755)neuregulin receptor activity (GO:0038131)neuregulin receptor activity (GO:0038131)neuromuscular junction (GO:0031594)neuron differentiation (GO:0030182)neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0099645)nucleoplasm (GO:0005654)nucleus (GO:0005634)nucleus (GO:0005634)olfactory bulb interneuron differentiation (GO:0021889)olfactory bulb interneuron differentiation (GO:0021889)organelle (GO:0043226)peptidyl-tyrosine phosphorylation (GO:0018108)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)positive regulation of DNA-templated transcription (GO:0045893)positive regulation of DNA-templated transcription (GO:0045893)positive regulation of ERK1 and ERK2 cascade (GO:0070374)positive regulation of ERK1 and ERK2 cascade (GO:0070374)positive regulation of MAPK cascade (GO:0043410)positive regulation of cardiac muscle cell proliferation (GO:0060045)positive regulation of cardiac muscle cell proliferation (GO:0060045)positive regulation of cell population proliferation (GO:0008284)positive regulation of cell population proliferation (GO:0008284)positive regulation of epithelial cell proliferation (GO:0050679)positive regulation of phosphate metabolic process (GO:0045937)positive regulation of protein phosphorylation (GO:0001934)positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427)positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427)positive regulation of tyrosine phosphorylation of STAT protein (GO:0042531)postsynaptic density membrane (GO:0098839)postsynaptic membrane (GO:0045211)presynaptic membrane (GO:0042734)protein autophosphorylation (GO:0046777)protein binding (GO:0005515)protein homodimerization activity (GO:0042803)protein kinase activity (GO:0004672)protein tyrosine kinase activity (GO:0004713)protein tyrosine kinase activity (GO:0004713)regulation of cell migration (GO:0030334)regulation of cell migration (GO:0030334)signal transduction (GO:0007165)signaling receptor complex (GO:0043235)signaling receptor complex (GO:0043235)synapse assembly (GO:0007416)transcription cis-regulatory region binding (GO:0000976)transmembrane receptor protein tyrosine kinase activity (GO:0004714)transmembrane receptor protein tyrosine kinase activity (GO:0004714)transmembrane receptor protein tyrosine kinase activity (GO:0004714)transmembrane receptor protein tyrosine kinase activity (GO:0004714)
Expression (TPM)
ERBB4 — as a Regulated Gene

TFs regulating ERBB4 0 TFs

Transcription factors with Perturb-seq knockdown data for ERBB4. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = ERBB4 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to ERBB4

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of ERBB4, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility Element Dist. to TSS Link type TFs
chr2:211,331,626–211,332,499 1097.4 kb Distal (>10kb) Multiome HiCAR 183
chr2:211,591,405–211,592,804 837.1 kb Distal (>10kb) Multiome HiCAR 109
chr2:211,742,926–211,744,057 685.7 kb Distal (>10kb) Multiome HiCAR 147
chr2:211,766,641–211,767,274 662.4 kb Distal (>10kb) Multiome HiCAR 187
chr2:212,426,722–212,427,290 2.0 kb Proximal (<10kb) 23
chr2:212,428,776–212,429,503 at TSS At TSS 176
chr2:212,536,027–212,539,802 110.0 kb Distal (>10kb) Multiome 723
chr2:212,548,566–212,548,816 9.7 kb Proximal (<10kb) 41

Genome Browser

Genomic view of the ERBB4 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.

chr2:211,321,626 – 212,558,816
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq