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General Comment |
Kraus et al. (1989) detected a DNA fragment related to but distinct from epidermal growth factor receptor (EGFR) and ERBB2. cDNA cloning showed a predicted 148-kD transmembrane polypeptide with structural
features identifying it as a member of the ERBB gene family, prompting the designation ERBB3. Markedly elevated
ERBB3 mRNA levels were demonstrated in certain human mammary tumor cell lines, suggesting that it may play a role
in some human malignancies just as does EGFR (which is identical to what was previously called ERBB1).
Carraway et al. (1994) demonstrated that ERBB3 is a receptor for heregulin (142445) and is capable of mediating
HGL-stimulated tyrosine phosphorylation of itself.
NCBI Summary:
This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized. [provided by RefSeq, Jul 2008]
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Comment |
Neilson L, et al 200 reported molecular phenotyping of the human oocyte by PCR-SAGE.
Consecutive application of PCR and serial analysis of gene expression (SAGE) was used to generate a
catalog of approximately 50,000 SAGEtags from nine human oocytes. Matches for known genes were
identified using the National Institutes of Health SAGEtag database. Matches in the oocyte SAGE catalog
were found for surface receptors, second-messenger systems, and cytoskeletal, apoptotic, and secreted
proteins, including the soluble form of ERBB3 gene decribed here.
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Mutations |
1 mutations
Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Day FR et al. (2016) Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, yet there is little consensus regarding its aetiology. Here we perform a genome-wide association study of PCOS in up to 5,184 self-reported cases of White European ancestry and 82,759 controls, with follow-up in a further ∼2,000 clinically validated cases and ∼100,000 controls. We identify six signals for PCOS at genome-wide statistical significance (P<5 × 10(-8)), in/near genes ERBB4/HER4, YAP1, THADA, FSHB, RAD50 and KRR1. Variants in/near three of the four epidermal growth factor receptor genes (ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are associated with PCOS at or near genome-wide significance. Mendelian randomization analyses indicate causal roles in PCOS aetiology for higher BMI (P=2.5 × 10(-9)), higher insulin resistance (P=6 × 10(-4)) and lower serum sex hormone binding globulin concentrations (P=5 × 10(-4)). Furthermore, genetic susceptibility to later menopause is associated with higher PCOS risk (P=1.6 × 10(-8)) and PCOS-susceptibility alleles are associated with higher serum anti-Müllerian hormone concentrations in girls (P=8.9 × 10(-5)). This large-scale study implicates an aetiological role of the epidermal growth factor receptors, infers causal mechanisms relevant to clinical management and prevention, and suggests balancing selection mechanisms involved in PCOS risk. //////////////////
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