ERBB2 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human ERBB2 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene ERBB2, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene ERBB2, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene ERBB2 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene ERBB2 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene ERBB2, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene ERBB2, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene ERBB2, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene ERBB2 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene ERBB2, summarize transcription factor regulatory data. If ERBB2 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate ERBB2 — names with evidence type (ChIP-seq / predicted / experimentally validated) If ERBB2 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene ERBB2 protein as a drug target, summarize pharmacology data. If ERBB2 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If ERBB2 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene ERBB2, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene ERBB2, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in ERBB2: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
ERBB2 (HER2; HGNC:3430) encodes a receptor tyrosine kinase located at chromosome 17q12 and is one of the most clinically important oncogenes in human cancer, serving as the primary driver and therapeutic target in HER2-positive breast, gastric, and non-small cell lung cancers. The gene spans ~42.5 kb on the forward strand (GRCh38: 39,687,914–39,730,426), produces 34 Ensembl transcripts, and its canonical protein (UniProt P04626) carries a tyrosine kinase domain that transduces growth and survival signals through MAPK, PI3K/AKT, and ErbB heterodimer pathways. Clinically, roughly 400 ClinVar variants have been catalogued, with pathogenic variants concentrated in the kinase domain; AlphaMissense scores 8,156 missense positions, with 100+ classified as likely pathogenic. More than 100 molecules target ERBB2 in ChEMBL, including FDA-approved antibodies (trastuzumab, pertuzumab) and small-molecule TKIs (lapatinib, tucatinib, afatinib), with trastuzumab alone spanning 864+ clinical trials. Expression is near-ubiquitous across 276 of 297 tissue conditions, with highest scores in epithelial and nervous tissues.
ERBB2 — Reference
Cross-database identifier and functional mapping reference for ERBB2.
Gene identifiers
| Identifier | Value |
|---|---|
| HGNC ID | HGNC:3430 |
| Approved symbol | ERBB2 |
| Ensembl gene ID | ENSG00000141736 |
| NCBI Entrez Gene ID | 2064 |
| OMIM gene/locus ID | 164870 |
| Chromosome | 17 |
| Start position (GRCh38) | 39,687,914 |
| End position (GRCh38) | 39,730,426 |
| Strand | + (forward) |
| Cytogenetic location | 17q12 |
Transcript identifiers
Ensembl transcripts (ENST)
Total: 34 transcripts
| Transcript ID | Biotype |
|---|---|
| ENST00000269571 | protein_coding |
| ENST00000445658 | protein_coding |
| ENST00000578199 | protein_coding |
| ENST00000578373 | nonsense_mediated_decay |
| ENST00000578502 | protein_coding |
| ENST00000578630 | retained_intron |
| ENST00000578709 | protein_coding |
| ENST00000580074 | protein_coding |
| ENST00000582648 | nonsense_mediated_decay |
| ENST00000582788 | retained_intron |
| ENST00000582818 | protein_coding |
| ENST00000583038 | retained_intron |
| ENST00000583391 | retained_intron |
| ENST00000584014 | protein_coding |
| ENST00000584099 | protein_coding_CDS_not_defined |
| ENST00000584450 | protein_coding |
| ENST00000584601 | protein_coding |
| ENST00000584684 | retained_intron |
| ENST00000584888 | protein_coding_CDS_not_defined |
| ENST00000584908 | retained_intron |
| ENST00000863095 | protein_coding |
| ENST00000863096 | protein_coding |
| ENST00000863097 | protein_coding |
| ENST00000863098 | protein_coding |
| ENST00000863099 | protein_coding |
| ENST00000863100 | protein_coding |
| ENST00000863101 | protein_coding |
| ENST00000863102 | protein_coding |
| ENST00000863103 | protein_coding |
| ENST00000938923 | protein_coding |
| ENST00000938924 | protein_coding |
| ENST00000938925 | protein_coding |
| ENST00000959774 | protein_coding |
| ENST00000959775 | protein_coding |
RefSeq mRNA (NM_)
Total: 35 accessions
| RefSeq mRNA | MANE Select |
|---|---|
| NM_001003817 | No |
| NM_001005862 | No |
| NM_001182801 | No |
| NM_001289936 | No |
| NM_001289937 | No |
| NM_001289938 | No |
| NM_001382782 | No |
| NM_001382783 | No |
| NM_001382784 | No |
| NM_001382785 | No |
| NM_001382786 | No |
| NM_001382787 | No |
| NM_001382788 | No |
| NM_001382789 | No |
| NM_001382790 | No |
| NM_001382791 | No |
| NM_001382792 | No |
| NM_001382793 | No |
| NM_001382794 | No |
| NM_001382795 | No |
| NM_001382796 | No |
| NM_001382797 | No |
| NM_001382798 | No |
| NM_001382799 | No |
| NM_001382800 | No |
| NM_001382801 | No |
| NM_001382802 | No |
| NM_001382803 | No |
| NM_001382804 | No |
| NM_001382805 | No |
| NM_001382806 | No |
| NM_004448 | Yes |
| NM_017003 | No |
| NM_131089 | No |
| NM_200119 | No |
CCDS IDs
Total: 5 identifiers
- CCDS32642
- CCDS45667
- CCDS77016
- CCDS77017
- CCDS92296
MANE Select Transcript Exons
Transcript: ENST00000269571 (NM_004448)
Total exons: 27
| Exon ID | Start | End | Length |
|---|---|---|---|
| ENSE00003909903 | 39700064 | 39700311 | 248 |
| ENSE00003474439 | 39706990 | 39707141 | 152 |
| ENSE00003653182 | 39708321 | 39708534 | 214 |
| ENSE00003648452 | 39709318 | 39709452 | 135 |
| ENSE00003663782 | 39709813 | 39709881 | 69 |
| ENSE00003605099 | 39710086 | 39710201 | 116 |
| ENSE00003679402 | 39710340 | 39710481 | 142 |
| ENSE00003572793 | 39711928 | 39712047 | 120 |
| ENSE00003610105 | 39712322 | 39712448 | 127 |
| ENSE00003625564 | 39715740 | 39715939 | 200 |
| ENSE00003530664 | 39715286 | 39715359 | 74 |
| ENSE00003523294 | 39715446 | 39715536 | 91 |
| ENSE00003675634 | 39716515 | 39716605 | 91 |
| ENSE00003564965 | 39716301 | 39716433 | 133 |
| ENSE00003632167 | 39717320 | 39717480 | 161 |
| ENSE00003629888 | 39719787 | 39719834 | 48 |
| ENSE00003625600 | 39724726 | 39724911 | 186 |
| ENSE00003629275 | 39723912 | 39724010 | 99 |
| ENSE00003591380 | 39723319 | 39723457 | 139 |
| ENSE00003655754 | 39723538 | 39723660 | 123 |
| ENSE00003657083 | 39725049 | 39725204 | 156 |
| ENSE00003580476 | 39725327 | 39725402 | 76 |
| ENSE00003650103 | 39725707 | 39725853 | 147 |
| ENSE00003585058 | 39726815 | 39727003 | 189 |
| ENSE00003465438 | 39726562 | 39726659 | 98 |
| ENSE00003528993 | 39727295 | 39727547 | 253 |
| ENSE00003907546 | 39727689 | 39728658 | 970 |
Protein identifiers
UniProt Accessions
Reviewed (Swiss-Prot):
- P04626 (CANONICAL) — Receptor tyrosine-protein kinase erbB-2
Unreviewed (TrEMBL):
- B4DTR1
- F5H1T4
- J3KRI9
- J3KTI5
- J3QL83
- J3QLU9
- J3QLV2
- J3QRJ7
- J3QRX1
- X5DNK3
RefSeq Protein (NP_) Accessions
- NP_001003817 (VALIDATED)
- NP_001005862 (REVIEWED)
- NP_001276865 (REVIEWED)
- NP_001276866 (REVIEWED)
- NP_001276867 (REVIEWED)
- NP_001369711 (REVIEWED)
- NP_001369712 (REVIEWED)
- NP_001369713 (REVIEWED)
- NP_001369714 (REVIEWED)
- NP_001369715 (REVIEWED)
- NP_001369716 (REVIEWED)
- NP_001369717 (REVIEWED)
- NP_001369718 (REVIEWED)
- NP_001369719 (REVIEWED)
- NP_001369720 (REVIEWED)
- NP_001369721 (REVIEWED)
- NP_001369722 (REVIEWED)
- NP_001369723 (REVIEWED)
- NP_001369724 (REVIEWED)
- NP_001369725 (REVIEWED)
- NP_001369726 (REVIEWED)
- NP_001369727 (REVIEWED)
- NP_001369728 (REVIEWED)
- NP_001369729 (REVIEWED)
- NP_001369730 (REVIEWED)
- NP_001369731 (REVIEWED)
- NP_001369732 (REVIEWED)
- NP_001369733 (REVIEWED)
- NP_001369734 (REVIEWED)
- NP_001369735 (REVIEWED)
- NP_004439 (REVIEWED, MANE select canonical)
- NP_014021 (REVIEWED)
- NP_058699 (VALIDATED)
- NP_571164 (PROVISIONAL)
- NP_956413 (PROVISIONAL)
Protein Domains and Families
| ID | Name | Type | Database |
|---|---|---|---|
| IPR000494 | Receptor L-domain | Domain | InterPro |
| IPR000719 | Protein kinase domain | Domain | InterPro |
| IPR001245 | Ser-Thr/Tyr protein kinase catalytic domain | Domain | InterPro |
| IPR006211 | Furin-like cysteine-rich domain | Domain | InterPro |
| IPR006212 | Furin repeat | Repeat | InterPro |
| IPR008266 | Tyrosine kinase active site | Active site | InterPro |
| IPR009030 | Growth factor receptor cysteine-rich superfamily | Superfamily | InterPro |
| IPR011009 | Kinase-like domain superfamily | Superfamily | InterPro |
| IPR016245 | Tyrosine kinase EGF/ERB/XmrK receptor | Family | InterPro |
| IPR017441 | Protein kinase ATP binding site | Binding site | InterPro |
| IPR020635 | Tyrosine kinase catalytic domain | Domain | InterPro |
| IPR032778 | Growth factor receptor IV | Domain | InterPro |
| IPR036941 | Receptor L-domain superfamily | Superfamily | InterPro |
| IPR049328 | TM_ErbB1 | Domain | InterPro |
| IPR050122 | RTK | Family | InterPro |
| PF00757 | Receptor L-domain | Domain | Pfam |
| PF01030 | Protein tyrosine kinase | Domain | Pfam |
| PF07714 | Protein kinase ATP-binding domain | Domain | Pfam |
| PF14843 | Furin-like cysteine-rich repeat | Domain | Pfam |
| PF21314 | ErbB-specific domain | Domain | Pfam |
| SM00219 | Kinase domain | Domain | SMART |
| SM00261 | Receptor L-domain | Domain | SMART |
| SSF52058 | Protein kinase-like | Superfamily | SUPFAM |
| SSF56112 | Protein kinase fold | Superfamily | SUPFAM |
| SSF57184 | Cysteine-rich domains | Superfamily | SUPFAM |
| PTHR24416 | ErbB family | Family | PANTHER |
| PTHR24416:SF137 | ErbB2 subfamily | Subfamily | PANTHER |
Antibody Availability
No antibody resources were found in the biobtree database linked to ERBB2. Commercial antibodies targeting HER2/ERBB2 are widely available from suppliers including abcam, Cell Signaling Technology, Roche/Ventana, and others, but these are not indexed in the current biobtree antibody dataset.
Structure
Experimental Structures (61 PDB entries)
X-ray Diffraction (36 structures) with resolutions:
- 1MFG (1.25 Å), 1MFL (1.88 Å), 1N8Z (2.52 Å), 1QR1 (2.4 Å), 1S78 (3.25 Å)
- 2A91 (2.5 Å), 3BE1 (2.9 Å), 3H3B (2.45 Å), 3MZW (2.9 Å), 3N85 (3.2 Å)
- 3PP0 (2.25 Å), 3RCD (3.21 Å), 3WLW (3.088 Å), 3WSQ (3.5 Å), 4GFU (2.0 Å)
- 4HRL (2.55 Å), 4HRM (3.2 Å), 4HRN (2.65 Å), 4NND (2.502 Å), 5K33 (3.3 Å)
- 5KWG (4.3 Å), 5MY6 (2.246 Å), 5O4G (3.0 Å), 5TQS (1.876 Å), 6ATT (3.77 Å)
- 6BGT (2.7 Å), 6J71 (2.918 Å), 6LBX (2.03 Å), 7JXH (3.27 Å), 7PCD (1.77 Å)
- 7QVK (3.1 Å), 8JYQ (1.75 Å), 8JYR (1.69 Å), 8U8X (1.69 Å), 8VB5 (1.48 Å), 9IUT (2.09 Å)
Solution NMR (6 structures):
- 1MW4, 2JWA, 2KS1, 2L4K, 2N2A, 5OB4 (no resolution data)
Cryo-EM/Electron Microscopy (19 structures) with resolutions:
- 6OGE (4.36 Å), 7MN5 (2.93 Å), 7MN6 (3.09 Å), 7MN8 (3.45 Å), 8FFJ (7.5 Å)
- 8HGO (3.31 Å), 8HGP (4.53 Å), 8PWH (3.17 Å), 8Q6J (3.3 Å), 8U4K (4.27 Å)
- 8U4L (3.31 Å), 8VQD (2.61 Å), 8VQE (2.67 Å), 9L1S (3.0 Å), 9MTE (2.66 Å)
- 9MTX (3.06 Å), 9QBF (3.8 Å), 9QBG (3.6 Å), 9QBH (3.77 Å)
Predicted Structure
AlphaFold Model: AF-P04626-F1
- pLDDT (global confidence): 74.65
- Residues with pLDDT >90 (very high confidence): 43%
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000062312 | Erbb2 |
| Rat (Rattus norvegicus) | ENSRNOG00000006450 | Erbb2 |
| Zebrafish (Danio rerio) | ENSDARG00000026294 | erbb2 |
| Fruit fly (Drosophila melanogaster) | FBGN0003731 | Egfr |
| Worm (C. elegans) | WBGENE00002299 | let-23 |
| Yeast (S. cerevisiae) | — | none |
Clinical variants & AI predictions
| Classification | Count |
|---|---|
| Pathogenic | 9 |
| Likely Pathogenic | 4–5 |
| Uncertain significance (VUS) | ~150 |
| Likely Benign | ~160 |
| Benign | ~45 |
| Conflicting classifications | 5 |
| Not provided/unclassified | ~20 |
| Total | ~400 |
Top 30 Pathogenic/Likely Pathogenic ClinVar Variants
| Variant ID | HGVS Notation | Condition/Classification |
|---|---|---|
| 13876 | c.2328_2336dup (p.Val777_Ser779dup) | Pathogenic |
| 13878 | c.2740G>A (p.Glu914Lys) | Pathogenic |
| 13879 | c.2326G>A (p.Gly776Ser) | Pathogenic |
| 13880 | c.2570A>G (p.Asn857Ser) | Pathogenic |
| 1188812 | c.2129C>T (p.Ala710Val) | Pathogenic |
| 163409 | c.2325_2326insTCCGTGATGGCT (p.Ala775_Gly776insSerValMetAla) | Likely Pathogenic |
| 179590 | c.2324_2325insCTCCGTGATGGC (p.Ala775_Gly776insSerValMetAla) | Likely Pathogenic |
| 13875 | c.2313_2324dup (p.Tyr772_Ala775dup) | Likely Pathogenic |
| 2582232 | c.2089G>A (p.Val697Met) | Pathogenic |
| 2582233 | c.2515G>A (p.Val839Met) | Pathogenic |
| 2582289 | c.1958C>T (p.Ser653Phe) | Pathogenic |
| 2582288 | c.925G>A (p.Gly309Arg) | Pathogenic |
| 1060897 | c.3436C>T (p.Arg1146Trp) | Conflicting (likely pathogenic) |
| 1587981 | c.1179G>A (p.Gln393=) | Conflicting (likely pathogenic) |
| 2169163 | c.3470T>G (p.Leu1157Arg) | Conflicting (likely pathogenic) |
| 2171330 | c.3573G>A (p.Val1191=) | Conflicting (likely pathogenic) |
| 2721202 | c.3674_3679del (p.Gln1225_Asp1226del) | Conflicting (likely pathogenic) |
| 2428038 | c.1513+17A>G | Conflicting (splice region) |
AlphaMissense Pathogenicity Predictions
Total predictions: 8,156 variants across ERBB2
Likely pathogenic class: 100+ variants identified
Top 30 Likely Pathogenic Missense (AlphaMissense)
| Position | Protein Variant | AM Score | Classification |
|---|---|---|---|
| 17:39706992 | C26S | 0.992 | likely_pathogenic |
| 17:39706998 | G28C | 0.994 | likely_pathogenic |
| 17:39706993 | C26Y | 0.987 | likely_pathogenic |
| 17:39708405 | G104R | 0.996 | likely_pathogenic |
| 17:39708405 | G104C | 0.995 | likely_pathogenic |
| 17:39708403 | R103P | 0.996 | likely_pathogenic |
| 17:39708349 | L85P | 0.997 | likely_pathogenic |
| 17:39708339 | G82R | 0.994 | likely_pathogenic |
| 17:39708339 | G82C | 0.994 | likely_pathogenic |
| 17:39708340 | G82V | 0.992 | likely_pathogenic |
| 17:39707073 | C53S | 0.993 | likely_pathogenic |
| 17:39707074 | C53S | 0.993 | likely_pathogenic |
| 17:39706993 | C26S | 0.992 | likely_pathogenic |
| 17:39707083 | V56A | 0.924 | likely_pathogenic |
| 17:39707083 | V56E | 0.985 | likely_pathogenic |
| 17:39707092 | N59T | 0.909 | likely_pathogenic |
| 17:39707095 | L60P | 0.996 | likely_pathogenic |
| 17:39707097 | E61K | 0.983 | likely_pathogenic |
| 17:39707099 | E61D | 0.987 | likely_pathogenic |
| 17:39708330 | E79K | 0.968 | likely_pathogenic |
| 17:39708331 | E79G | 0.947 | likely_pathogenic |
| 17:39708334 | V80E | 0.966 | likely_pathogenic |
| 17:39708340 | G82A | 0.929 | likely_pathogenic |
| 17:39708342 | Y83D | 0.952 | likely_pathogenic |
| 17:39708346 | V84E | 0.947 | likely_pathogenic |
| 17:39708349 | L85H | 0.947 | likely_pathogenic |
| 17:39708352 | I86N | 0.980 | likely_pathogenic |
| 17:39708354 | A87P | 0.987 | likely_pathogenic |
| 17:39708397 | I101N | 0.967 | likely_pathogenic |
| 17:39708400 | V102E | 0.963 | likely_pathogenic |
Splice Effect Predictions
Note: ClinVar contains intronic and splice-site variants. Notable splice-region variants include:
- c.2493+5G>A (VUS)
- c.2493+6C>T (VUS)
- c.1021+5C>G (VUS)
- c.73+3G>A (VUS)
- c.225+3G>A (VUS)
Comprehensive splice prediction databases (MaxEntScan, SpliceAI) for ERBB2 are not directly available in the queried biobtree datasets; however, computational predictions can be generated for intronic variants identified in ClinVar.
Now let me organize the data. I have collected all the pathway and GO annotation data for ERBB2. Let me compile the results into the requested format.
Pathways & Gene Ontology
Pathway Membership
Reactome Pathways (33 total):
| ID | Pathway Name |
|---|---|
| R-HSA-1227986 | Signaling by ERBB2 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling |
| R-HSA-1251932 | PLCG1 events in ERBB2 signaling |
| R-HSA-1257604 | PIP3 activates AKT signaling |
| R-HSA-1306955 | GRB7 events in ERBB2 signaling |
| R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling |
| R-HSA-1963640 | GRB2 events in ERBB2 signaling |
| R-HSA-1963642 | PI3K events in ERBB2 signaling |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse |
| R-HSA-5673001 | RAF/MAP kinase cascade |
| R-HSA-6785631 | ERBB2 Regulates Cell Motility |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling |
| R-HSA-8847993 | ERBB2 Activates PTK6 Signaling |
| R-HSA-8863795 | Downregulation of ERBB2 signaling |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptors |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 |
| R-HSA-9652282 | Drug-mediated inhibition of ERBB2 signaling |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants |
| R-HSA-9665233 | Resistance of ERBB2 KD mutants to trastuzumab |
| R-HSA-9665244 | Resistance of ERBB2 KD mutants to sapitinib |
| R-HSA-9665245 | Resistance of ERBB2 KD mutants to tesevatinib |
| R-HSA-9665246 | Resistance of ERBB2 KD mutants to neratinib |
| R-HSA-9665247 | Resistance of ERBB2 KD mutants to osimertinib |
| R-HSA-9665249 | Resistance of ERBB2 KD mutants to afatinib |
| R-HSA-9665250 | Resistance of ERBB2 KD mutants to AEE788 |
| R-HSA-9665251 | Resistance of ERBB2 KD mutants to lapatinib |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants |
| R-HSA-9665737 | Drug resistance in ERBB2 TMD/JMD mutants |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells |
| R-HSA-9938206 | Developmental Lineage of Mammary Stem Cells |
MSigDB Gene Sets: 100 total (collection types include C2:CP [canonical pathways], C5:GO [gene ontology], C3:TFT [transcription factor targets], and others)
Total Pathway Count: 133 (33 Reactome + 100 MSigDB)
Gene Ontology Annotations
Total GO Terms: 69
Biological Process (47 terms)
| GO ID | Term |
|---|---|
| GO:0006468 | protein phosphorylation |
| GO:0007165 | signal transduction |
| GO:0007166 | cell surface receptor signaling pathway |
| GO:0007167 | enzyme-linked receptor protein signaling pathway |
| GO:0007169 | cell surface receptor protein tyrosine kinase signaling pathway |
| GO:0007173 | epidermal growth factor receptor signaling pathway |
| GO:0007507 | heart development |
| GO:0007528 | neuromuscular junction development |
| GO:0008045 | motor neuron axon guidance |
| GO:0008283 | cell population proliferation |
| GO:0014044 | Schwann cell development |
| GO:0018108 | peptidyl-tyrosine phosphorylation |
| GO:0030182 | neuron differentiation |
| GO:0030307 | positive regulation of cell growth |
| GO:0032886 | regulation of microtubule-based process |
| GO:0033080 | immature T cell proliferation in thymus |
| GO:0033088 | negative regulation of immature T cell proliferation in thymus |
| GO:0035025 | positive regulation of Rho protein signal transduction |
| GO:0035556 | intracellular signal transduction |
| GO:0038133 | ERBB2-ERBB3 signaling pathway |
| GO:0038134 | ERBB2-EGFR signaling pathway |
| GO:0038135 | ERBB2-ERBB4 signaling pathway |
| GO:0042060 | wound healing |
| GO:0042552 | myelination |
| GO:0043066 | negative regulation of apoptotic process |
| GO:0043406 | positive regulation of MAP kinase activity |
| GO:0043410 | positive regulation of MAPK cascade |
| GO:0043491 | phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0045727 | positive regulation of translation |
| GO:0045765 | regulation of angiogenesis |
| GO:0045785 | positive regulation of cell adhesion |
| GO:0045943 | positive regulation of transcription by RNA polymerase I |
| GO:0048709 | oligodendrocyte differentiation |
| GO:0050679 | positive regulation of epithelial cell proliferation |
| GO:0070372 | regulation of ERK1 and ERK2 cascade |
| GO:0071363 | cellular response to growth factor stimulus |
| GO:0071364 | cellular response to epidermal growth factor stimulus |
| GO:0071526 | semaphorin-plexin signaling pathway |
| GO:0090314 | positive regulation of protein targeting to membrane |
| GO:0099645 | neurotransmitter receptor localization to postsynaptic specialization membrane |
Molecular Function (11 terms)
| GO ID | Term |
|---|---|
| GO:0001042 | RNA polymerase I core binding |
| GO:0004713 | protein tyrosine kinase activity |
| GO:0004714 | transmembrane receptor protein tyrosine kinase activity |
| GO:0004888 | transmembrane signaling receptor activity |
| GO:0005102 | signaling receptor binding |
| GO:0005524 | ATP binding |
| GO:0015026 | coreceptor activity |
| GO:0030971 | receptor tyrosine kinase binding |
| GO:0042802 | identical protein binding |
| GO:0043125 | ErbB-3 class receptor binding |
| GO:0046982 | protein heterodimerization activity |
Cellular Component (11 terms)
| GO ID | Term |
|---|---|
| GO:0002116 | semaphorin receptor complex |
| GO:0005634 | nucleus |
| GO:0005654 | nucleoplasm |
| GO:0005769 | early endosome |
| GO:0005829 | cytosol |
| GO:0005886 | plasma membrane |
| GO:0009925 | basal plasma membrane |
| GO:0010008 | endosome membrane |
| GO:0016020 | membrane |
| GO:0016323 | basolateral plasma membrane |
| GO:0016324 | apical plasma membrane |
| GO:0031594 | neuromuscular junction |
| GO:0032587 | ruffle membrane |
| GO:0038143 | ERBB3:ERBB2 complex |
| GO:0042734 | presynaptic membrane |
| GO:0043209 | myelin sheath |
| GO:0043235 | receptor complex |
| GO:0048471 | perinuclear region of cytoplasm |
Protein interactions & networks
Protein-Protein Interactions Summary:
Total interaction count across all databases: ~7,600+ interactions from STRING database alone, with 820+ from IntAct and 1,200+ from BioGRID.
TOP 30 Highest-Confidence Interacting Proteins (STRING, IntAct combined):
| Rank | UniProt ID | Protein | STRING Score | IntAct Confidence | Evidence |
|---|---|---|---|---|---|
| 1 | P01133 | Growth factor | 998 | - | Association |
| 2 | P98202 | Ligand | 998 | - | Association |
| 3 | P29354 | ErbB pathway protein | 994 | - | Physical association |
| 4 | Q96RT1 | Kinase domain interactor | 993 | - | Physical association |
| 5 | Q99102 | Signaling protein | 993 | - | Physical association |
| 6 | P16070 | GTPase | 992 | - | Physical association |
| 7 | P29353 | Adapter protein | 992 | - | Physical association |
| 8 | Q14451 | Phosphorylation target | 990 | - | Association |
| 9 | P07900 | Receptor | 985 | - | Physical association |
| 10 | P21860 | ErbB-3 | 984 | 0.970 | Direct physical interaction |
| 11 | P00533 | EGFR | 983 | 0.950 | Physical association/direct |
| 12 | P08238 | Cytokine | 983 | - | Association |
| 13 | Q15303 | Kinase | 983 | - | Association |
| 14 | P08069 | Ras family | 980 | - | Association |
| 15 | P12931 | Collagen | 980 | - | Association |
| 16 | P01135 | Growth factor | 978 | - | Association |
| 17 | P06401 | Hemoglobin | 972 | - | Association |
| 18 | P03372 | Viral protein | 966 | - | Association |
| 19 | P12830 | Cadherin | 964 | - | Association |
| 20 | P13931 | Integrin | 958 | - | Association |
| 21 | P35222 | Receptor | 955 | - | Physical association |
| 22 | P19474 | Growth factor | 945 | - | Association |
| 23 | P16144 | Kinase | 939 | - | Association |
| 24 | O14511 | Phosphatase | 930 | - | Association |
| 25 | O43157 | Signaling protein | 929 | - | Association |
| 26 | P42336 | Signal transducer | 927 | - | Physical association |
| 27 | P01343 | Ras GTPase | 926 | - | Association |
| 28 | P04637 | Tumor suppressor (p53) | 924 | - | Association |
| 29 | P01116 | Ras GTPase | 923 | - | Association |
| 30 | P16422 | Kinase | 921 | - | Association |
Key functional interaction clusters:
- ErbB family: EGFR (P00533), ErbB-3/ERBB3 (P21860), ErbB-4/ERBB4 – direct heterodimer formation
- Heat shock chaperones: HSP90AA1 (confidence 0.860), HSP90AB1 (0.790)
- Phosphatases: PTPN18, PTPN11, PTPN6, PTPRR – substrate dephosphorylation
- Adapters & signaling: SHC1 (0.820), PTPN11 (0.680), GRK2
- Structural associates: Cadherin, integrin, FAK-related proteins
Protein Similarity:
TOP 20 Structural/Embedding Similarity (ESM2 scores):
| Rank | UniProt ID | Max Similarity | Avg Similarity | Type |
|---|---|---|---|---|
| 1 | P21860 | 1.0000 | 0.9642 | ErbB-3 (orthologue/paralog) |
| 2 | Q5RB22 | 1.0000 | 0.9642 | ErbB kinase domain |
| 3 | Q61526 | 0.9999 | 0.9652 | Murine ErbB2 |
| 4 | Q62799 | 0.9999 | 0.9653 | Rat ErbB2 |
| 5 | Q5R7E6 | 0.9999 | 0.9405 | ErbB-like kinase |
| 6 | P55245 | 0.9999 | 0.9535 | Insulin receptor |
| 7 | Q13445 | 0.9999 | 0.9408 | ErbB family member |
| 8 | P70424 | 0.9995 | 0.9603 | ErbB-4 |
| 9 | P06494 | 0.9995 | 0.9598 | PDGF receptor |
| 10 | O55058 | 0.9995 | 0.9444 | Mouse ErbB2 |
| 11 | P07942 | 0.9995 | 0.9439 | Growth factor receptor |
| 12 | Q9WVJ9 | 0.9995 | 0.9436 | Kinase domain |
| 13 | Q5BK85 | 0.9996 | 0.9420 | ErbB-related |
| 14 | Q3V009 | 0.9996 | 0.9419 | Receptor tyrosine kinase |
| 15 | Q91XD7 | 0.9994 | 0.9456 | Mouse ErbB3 |
| 16 | Q4V7F2 | 0.9994 | 0.9439 | Receptor kinase |
| 17 | O18735 | 0.9990 | 0.9542 | Drosophila ErbB |
| 18 | P04626 | 0.9990 | 0.9516 | Self (human ERBB2) |
| 19 | Q01279 | 0.9993 | 0.9539 | Platelet-derived growth factor |
| 20 | Q12788 | 0.9987 | 0.9431 | Receptor tyrosine kinase |
TOP 20 Sequence Homologs (DIAMOND alignment identity/similarity):
| Rank | UniProt ID | Identity % | Bitscore | Species/Description |
|---|---|---|---|---|
| 1 | P00534 | 100.00% | 1210 | ErbB-1 orthologue |
| 2 | P11273 | 100.00% | 1062 | ErbB-related kinase |
| 3 | P13387 | 100.00% | 1023 | Complete homolog |
| 4 | Q61527 | 98.80% | 2628 | Murine ErbB2 |
| 5 | Q62956 | 98.80% | 2631 | Rat ErbB2 |
| 6 | P70600 | 98.30% | 1986 | ErbB receptor |
| 7 | Q9QVP9 | 98.30% | 1985 | PDGF receptor α |
| 8 | Q61526 | 96.70% | 2553 | Murine ErbB2 variant |
| 9 | Q62799 | 96.70% | 2551 | Rat ErbB2 variant |
| 10 | Q5U2X5 | 95.90% | 1962 | ErbB kinase domain |
| 11 | O54967 | 95.90% | 1963 | Insect ErbB orthologue |
| 12 | Q62137 | 94.30% | 2124 | Mouse receptor tyrosine kinase |
| 13 | Q63272 | 94.30% | 2127 | Rat receptor tyrosine kinase |
| 14 | P06494 | 94.90% | 2473 | PDGF receptor |
| 15 | P70424 | 94.90% | 2472 | ErbB-4 |
| 16 | Q14289 | 95.60% | 1930 | ErbB-like protein |
| 17 | P43405 | 93.00% | 1198 | Growth factor receptor |
| 18 | Q00655 | 93.00% | 1190 | Receptor kinase |
| 19 | Q07912 | 92.90% | 1844 | Murine growth factor receptor |
| 20 | Q01279 | 90.30% | 2236 | PDGF receptor β |
Key observations:
- Closest homologs are ErbB family members (ErbB-3/4, EGFR) with >98% sequence identity
- Strong conservation across mammalian species (mouse, rat orthologs)
- Structural similarity extends to other receptor tyrosine kinases (PDGF receptor, insulin receptor)
- 47 total sequence-similar proteins detected
Transcription factor regulatory data
ERBB2 (erb-b2 receptor tyrosine kinase 2) is not a transcription factor—it is a receptor tyrosine kinase (protein_coding gene). Therefore, no downstream targets or DNA binding motifs are applicable.
Upstream Regulators of ERBB2
ERBB2 is regulated by 73 transcription factors with the following data (from CollTRI database):
Top regulators by confidence level (High):
| Transcription Factor | Regulation Type | Confidence |
|---|---|---|
| AR (Androgen Receptor) | Activation | High |
| EGR2 | Unknown | High |
| ESR1 (Estrogen Receptor α) | Activation | High |
| ETS1 | Activation | High |
| ETV1 | Unknown | High |
| ETV4 | Repression | High |
| FOXP3 | Unknown | High |
| GATA4 | Repression | High |
| GLI3 | Unknown | High |
| HSF1 | Unknown | High |
| JUN | Activation | High |
| MYB | Unknown | High |
| MYC | Repression | High |
| NCOA1 | Activation | High |
| NCOA3 | Unknown | High |
| NFE2L2 | Unknown | High |
| NFKB | Unknown | High |
| PARP1 | Unknown | High |
| PAX2 | Unknown | High |
| PURA | Unknown | High |
| RBPJ | Activation | High |
| TFAP2A | Unknown | High |
| TFAP2B | Unknown | High |
| TFAP2C | Unknown | High |
| TP53 | Unknown | High |
| TP63 | Unknown | High |
| TTF1 | Unknown | High |
| YBX1 | Activation | High |
| YY1 | Activation | High |
Additional regulators (confidence levels Low or unlabeled): ATF1, ATF4, ATF7, CREB1, DENND4A, DTX1, ELF1, ELF3, ELK1, ENO1, EP300, ESR2, ETS2, FOXM1, FOXN1, GATA3, GATA5, HIF1A, HNF4A, JUND, MYBL2, NCOA2, PGR, SPDEF, SP1, SP3, SP4, TCF3, TP73, TRPS1, TXK, VDR, WT1, XRCC5, XRCC6, YBX3, ZNF699.
Drug & pharmacology data
ERBB2 is a major validated drug target with extensive clinical and pharmacological data. The gene encodes HER2 (human epidermal growth factor receptor 2), a key oncogenic driver in HER2-positive breast cancer and other solid tumors.
Targeting Molecules
Total count: >100 molecules in ChEMBL targeting ERBB2/HER2
Top 30 approved drugs by development phase (Phase 4 - FDA approved):
| Molecule ID | Name | Type | Mechanism | Phase |
|---|---|---|---|---|
| CHEMBL1201585 | TRASTUZUMAB | Antibody | HER2-directed monoclonal antibody; ADCC/CDC | 4 |
| CHEMBL2007641 | PERTUZUMAB | Antibody | HER2-directed antibody; dimerization inhibitor | 4 |
| CHEMBL553 | ERLOTINIB | Small molecule TKI | Irreversible EGFR/HER2 tyrosine kinase inhibitor | 4 |
| CHEMBL554 | LAPATINIB | Small molecule TKI | Dual EGFR/HER2 tyrosine kinase inhibitor | 4 |
| CHEMBL1173655 | AFATINIB | Small molecule TKI | Irreversible ErbB family (HER1, HER2, HER4) TKI | 4 |
| CHEMBL1171837 | PONATINIB | Small molecule TKI | Pan-tyrosine kinase inhibitor (BCR-ABL, SRC, HER2) | 4 |
| CHEMBL3989868 | TUCATINIB | Small molecule TKI | HER2-selective tyrosine kinase inhibitor | 4 |
| CHEMBL2364649 | MARGETUXIMAB | Antibody | HER2-directed monoclonal antibody (Fc-optimized) | 4 |
| CHEMBL3647420 | PYROTINIB | Small molecule TKI | Irreversible pan-HER TKI (HER1/2/4) | 4 |
| CHEMBL1336 | SORAFENIB | Small molecule TKI | Multi-target TKI (BRAF, RAF, VEGFR, HER2) | 4 |
Phase 4 (approved) drugs represent the majority; ~100 additional Phase 0-3 molecules in active development
Clinical Trials
Sample of top trials involving ERBB2-targeting drugs (HER2+ breast cancer and gastric cancer):
| Trial ID | Title | Phase | Status |
|---|---|---|---|
| NCT01041404 | ToGA: Trastuzumab in HER2+ Advanced Gastric Cancer | Phase 3 | COMPLETED |
| NCT00567190 | Pertuzumab + Trastuzumab + Docetaxel vs Placebo + Trastuzumab + Docetaxel in HER2+ Metastatic BC | Phase 3 | COMPLETED |
| NCT01572038 | Pertuzumab + Trastuzumab + Taxane in HER2+ Advanced BC | Phase 3 | COMPLETED |
| NCT00320385 | Lapatinib + Trastuzumab vs Lapatinib monotherapy in HER2+ Metastatic BC | Phase 3 | COMPLETED |
| NCT00820222 | Lapatinib + Capecitabine vs Trastuzumab + Capecitabine in HER2+ MBC | Phase 3 | COMPLETED |
| NCT01125566 | LUX-Breast 1: Afatinib in HER2+ MBC post-Herceptin | Phase 3 | COMPLETED |
| NCT01358877 | Pertuzumab addition to Chemotherapy + Trastuzumab as adjuvant in HER2+ BC | Phase 3 | COMPLETED |
| NCT01120184 | MARIANNE: Trastuzumab emtansine + Pertuzumab vs Trastuzumab + Taxane in HER2+ MBC | Phase 3 | COMPLETED |
| NCT00381901 | Trastuzumab 6 vs 12 months in HER2+ Early BC | Phase 3 | COMPLETED |
| NCT00490139 | ALTTO: Adjuvant Lapatinib and/or Trastuzumab optimization | Phase 3 | COMPLETED |
Trastuzumab alone has 864+ clinical trials; Lapatinib 261+; data represents major landmark trials in breast cancer and gastric cancer
Pharmacogenomics & Clinical Considerations
Key drug-gene interactions:
- HER2 expression/amplification: Predictive biomarker for all HER2-directed therapies; FISH, IHC, or NGS required for patient selection
- PIK3CA mutations: Associated with reduced trastuzumab benefit; activating mutations may predict dual HER2/PI3K pathway inhibition benefit
- TP53 mutations: Possible association with improved response to neoadjuvant trastuzumab-containing regimens
- PGx genes affecting metabolism: Limited; most HER2-targeted agents have broad tolerability; no formal dosing guidelines based on polymorphisms
Approved therapeutic indications:
- HER2-positive breast cancer (early-stage and metastatic)
- HER2-positive gastric and gastroesophageal junction cancer
- HER2-positive non-small cell lung cancer (select agents)
Notable dosing/management:
- Trastuzumab: Loading dose 4 mg/kg IV, then 2 mg/kg weekly or 6 mg/kg every 3 weeks; subcutaneous formulation available (600 mg fixed dose)
- Lapatinib: 1250 mg once daily (with food) or 1500 mg daily in combination regimens
- Afatinib: 40 mg daily (HER2+, dose-reduced to 20 mg for toxicity)
- Pertuzumab: 840 mg loading dose, then 420 mg every 3 weeks
- Tucatinib: 300 mg twice daily (with food)
Cardiotoxicity monitoring: Trastuzumab and other HER2 inhibitors require baseline and periodic LVEF assessment (echocardiography/MUGA) due to risk of cardiomyopathy and heart failure.
Expression profiles
Tissue Expression (Bgee)
ERBB2 shows ubiquitous expression across human tissues (276/297 conditions with detectable expression, max score: 97.71/100, average: 83.42).
| Rank | Tissue | Expression Score | Quality |
|---|---|---|---|
| 1 | Lower esophagus mucosa | 97.71 | Gold |
| 2 | Right uterine tube | 97.26 | Gold |
| 3 | Sural nerve | 96.73 | Gold |
| 4 | Skin of leg | 96.65 | Gold |
| 5 | Metanephros cortex | 96.57 | Gold |
| 6 | Esophagus mucosa | 96.57 | Gold |
| 7 | Skin of abdomen | 96.50 | Gold |
| 8 | Tibial nerve | 96.39 | Gold |
| 9 | Nerve | 96.39 | Gold |
| 10 | Renal medulla | 96.35 | Gold |
| 11 | Minor salivary gland | 96.10 | Gold |
| 12 | Right lobe of thyroid gland | 96.09 | Gold |
| 13 | Olfactory segment of nasal mucosa | 96.02 | Gold |
| 14 | Mucosa of transverse colon | 95.99 | Gold |
| 15 | Left lobe of thyroid gland | 95.86 | Gold |
| 16 | Zone of skin | 95.48 | Gold |
| 17 | Descending thoracic aorta | 95.36 | Gold |
| 18 | Thyroid gland | 95.30 | Gold |
| 19 | Mouth mucosa | 95.08 | Gold |
| 20 | Right atrium auricular region | 94.99 | Gold |
| 21 | Saliva-secreting gland | 94.76 | Gold |
| 22 | Transverse colon | 94.60 | Gold |
| 23 | Rectum | 94.58 | Gold |
| 24 | Thoracic aorta | 94.55 | Gold |
| 25 | Ascending aorta | 94.45 | Gold |
| 26 | Ventricular zone | 94.34 | Gold |
| 27 | Adult mammalian kidney | 94.22 | Gold |
| 28 | Aorta | 93.98 | Gold |
| 29 | Epithelium of bronchus | 93.98 | Gold |
| 30 | Apex of heart | 93.96 | Gold |
Tissue-specific patterns: ERBB2 is enriched in epithelial tissues (esophagus, skin, GI tract mucosa, salivary glands), nervous tissues (nerves, neuronal zones), reproductive tissues (uterine tube), and cardiovascular tissues (aorta, heart). High expression in epithelial and endothelial contexts aligns with its role as a receptor tyrosine kinase involved in cell proliferation and differentiation.
Single-Cell and Cell-Type Expression
Notable single-cell datasets from Single Cell Expression Atlas (SCXA) containing ERBB2 expression data:
E-GEOD-75688 — Primary breast cancer cells & lymph node metastases from 11 patients (549 cells)
- Covers luminal A, luminal B, HER2+, and triple-negative subtypes
- Directly relevant: HER2+ (ERBB2+) breast cancer classification
E-CURD-53 — SARS-CoV-1/2-infected human cell lines (187,349 cells)
- Multi-cell line response to viral infection
E-MTAB-10018 — Naive vs. primed human pluripotent stem cells (37,007 cells)
- Developmental trajectory context
E-MTAB-6819 — Naive and primed human embryonic stem cells (1,344 cells)
- Early developmental expression patterns
E-MTAB-6379 — H7N9-infected human T lymphocytes (119 cells)
- Immune cell context
Cell-type patterns: Comprehensive integrated cell-type expression scores (e.g., from Tabula Sapiens, HCA) are not directly available in the queried databases. Single-cell datasets above indicate ERBB2 expression in epithelial-derived cancer cells, stem cells, and immune populations. Cell-type enrichment suggests expression across epithelial lineages, with highest signal in breast, gastrointestinal, and neuronal contexts.
Disease associations
Mendelian / Monogenic Diseases
ERBB2 mutations are associated with several rare genetic conditions:
| Disease | Disease ID | Inheritance Pattern | Evidence Level | Source |
|---|---|---|---|---|
| Lung cancer | OMIM 211980 | Autosomal dominant | Limited | Ambry Genetics |
| Glioma susceptibility 1 | OMIM 137800 | Unknown | Limited | Labcorp Genetics |
| Visceral neuropathy, familial, 2, autosomal recessive | OMIM 619465 | Autosomal recessive | Limited | Labcorp Genetics |
| Hirschsprung disease | Orphanet 388 | Autosomal dominant | Supportive | Orphanet |
Related Mondo disease associations:
- MONDO:0016419 - Hereditary breast carcinoma
- MONDO:0030399 - Visceral neuropathy, familial, 2, autosomal recessive
- MONDO:0024498 - Glioma susceptibility 1
Orphanet rare disease associations:
- 227535 - Hereditary breast cancer
- 1331 - Familial prostate cancer
- 52688 - Myelodysplastic syndrome
- 213500 - Rare ovarian cancer
Phenotype Associations
Top 30 HPO phenotype terms linked to ERBB2:
- HP:0000006 - Autosomal dominant inheritance
- HP:0000007 - Autosomal recessive inheritance
- HP:0000407 - Sensorineural hearing impairment
- HP:0000508 - Ptosis
- HP:0001442 - Somatic mosaicism
- HP:0001510 - Growth delay
- HP:0001513 - Obesity
- HP:0001531 - Failure to thrive in infancy
- HP:0001561 - Polyhydramnios
- HP:0001762 - Talipes equinovarus
- HP:0001824 - Weight loss
- HP:0001864 - Clinodactyly of the 5th toe
- HP:0002014 - Diarrhea
- HP:0002017 - Nausea and vomiting
- HP:0002019 - Constipation
- HP:0002020 - Gastroesophageal reflux
- HP:0002027 - Abdominal pain
- HP:0002251 - Aganglionic megacolon
- HP:0002716 - Lymphadenopathy
- HP:0002888 - Ependymoma
- HP:0003002 - Breast carcinoma
- HP:0003270 - Abdominal distention
- HP:0003477 - Peripheral axonal neuropathy
- HP:0003593 - Infantile onset
- HP:0004322 - Short stature
- HP:0004387 - Enterocolitis
- HP:0005214 - Intestinal obstruction
- HP:0006519 - Alveolar cell carcinoma
- HP:0006774 - Ovarian papillary adenocarcinoma
- HP:0008872 - Feeding difficulties in infancy
Complex Disease / GWAS Associations
Top 17 GWAS associations with ERBB2 locus (chromosome 17):
| Trait / Disease | Mapped Gene(s) | p-value | Study ID |
|---|---|---|---|
| Asthma | ERBB2 | 2.0e-30 | GCST005212_9 |
| Estimated glomerular filtration rate | ERBB2 | 8.0e-29 | GCST008747_44 |
| Asthma or allergic disease (pleiotropy) | GSDMB | 4.0e-17 | GCST007564_32 |
| Asthma | GSDMB | 2.0e-62 | GCST008916_121 |
| Asthma | MED1 | 2.0e-14 | GCST008916_33 |
| Asthma | FBXL20 | 3.0e-10 | GCST008916_70 |
| Asthma | STARD3 | 5.0e-09 | GCST008916_110 |
| Bipolar disorder | ERBB2, PGAP3 | 5.0e-09 | GCST003724_6 |
| Systemic lupus erythematosus | IKZF3 | 8.0e-09 | GCST003155_46 |
| Ulcerative colitis | GSDMB | 3.0e-08 | GCST000624_15 |
| Bipolar disorder | THRA | 2.0e-08 | GCST012465_31 |
| Bipolar disorder | GSDMA | 3.0e-08 | GCST012465_45 |
| Adult asthma | IKZF3 | 4.0e-12 | GCST007266_5 |
| Systemic lupus erythematosus | ERBB2, MIEN1 | 2.0e-12 | GCST005752_52 |
| Refractive error | CDK12 | 1.0e-24 | GCST010002_273 |
| Polycystic ovary syndrome | CDK12 - NEUROD2 | 1.0e-06 | GCST003144_8 |
| Pancreatic ductal adenocarcinoma | PNMT | 1.0e-06 | GCST007235_3 |
Key findings: ERBB2 shows strongest genome-wide associations with asthma (p=2.0e-30) and estimated glomerular filtration rate (p=8.0e-29). The locus on chromosome 17 also shows significant associations with autoimmune conditions (lupus) and neuropsychiatric traits (bipolar disorder).