Erythroleukemia, familial, susceptibility to

Summary

Erythroleukemia, familial, susceptibility to (MONDO:0007573) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	erythroleukemia, familial, susceptibility to
Mondo ID	MONDO:0007573
MeSH	C565039
OMIM	133180
UMLS	C5552985
MedGen	1790819
GARD	0027777
Is cancer (heuristic)	no

Also known as: erythroleukemia, familial, susceptibility to · hereditary acute erythroid leukaemia · hereditary acute erythroid leukemia

Data availability: 6 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › erythroleukemia, familial, susceptibility to

Related subtypes (116): mosaic variegated aneuploidy syndrome, tuberous sclerosis, hereditary breast ovarian cancer syndrome, hereditary multiple osteochondromas, nevoid basal cell carcinoma syndrome, leukemia, chronic lymphocytic, susceptibility to, 2, blue rubber bleb nevus, cherubism, Beckwith-Wiedemann syndrome, multiple self-healing squamous epithelioma, goiter, multinodular 1, with or without Sertoli-Leydig cell tumors, hyperparathyroidism 2 with jaw tumors, Kaposi sarcoma, susceptibility to, hereditary leiomyomatosis and renal cell cancer, susceptibility to uveal melanoma, melanoma and neural system tumor syndrome, nasopharyngeal carcinoma, susceptibility to, 2, WAGR syndrome, neuroblastoma, susceptibility to, 1, Rothmund-Thomson syndrome, mismatch repair cancer syndrome 1, Wiskott-Aldrich syndrome, N syndrome, hereditary thrombocytopenia and hematologic cancer predisposition syndrome, prostate cancer/brain cancer susceptibility, Brooke-Spiegler syndrome, pancreatic cancer, susceptibility to, 1, Carney-Stratakis syndrome, nasopharyngeal carcinoma, susceptibility to, 1, ovarian cancer, susceptibility to, 1, colorectal cancer, susceptibility to, 1, lung cancer susceptibility 1, leukemia, chronic lymphocytic, susceptibility to, 1, Kostmann syndrome, colorectal cancer, susceptibility to, 2, colorectal cancer, susceptibility to, 3, colorectal cancer, susceptibility to, 5, colorectal cancer, susceptibility to, 6, colorectal cancer, susceptibility to, 7, leukemia, chronic lymphocytic, susceptibility to, 3, leukemia, chronic lymphocytic, susceptibility to, 4, leukemia, chronic lymphocytic, susceptibility to, 5, lung cancer susceptibility 3, colorectal cancer, susceptibility to, 8, colorectal cancer, susceptibility to, 9, colorectal cancer, susceptibility to, 10, colorectal cancer, susceptibility to, 11, lung cancer susceptibility 4, neuroblastoma, susceptibility to, 3, neuroblastoma, susceptibility to, 4, neuroblastoma, susceptibility to, 5, neuroblastoma, susceptibility to, 6, leukemia, acute lymphocytic, susceptibility to, 1, leukemia, acute lymphocytic, susceptibility to, 2, lung cancer susceptibility 5, BAP1-related tumor predisposition syndrome, familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome, Maffucci syndrome, basal cell carcinoma, susceptibility to, 7, colorectal cancer, susceptibility to, 12, leukemia, acute lymphoblastic, susceptibility to, 3, cholangiocarcinoma, susceptibility to, progeroid features-hepatocellular carcinoma predisposition syndrome, neuroblastoma, susceptibility to, 7, DDX41-related hematologic malignancy predisposition syndrome, nasopharyngeal carcinoma, susceptibility to, 3, familial isolated hyperparathyroidism, intestinal polyposis syndrome, dyskeratosis congenita, familial rhabdoid tumor, multiple endocrine neoplasia, hereditary pheochromocytoma-paraganglioma, PTEN hamartoma tumor syndrome, familial multiple fibrofolliculoma, hereditary retinoblastoma, familial atypical multiple mole melanoma syndrome, hereditary nonpolyposis colon cancer, Li-Fraumeni syndrome, Cobb syndrome, neurofibromatosis, susceptibility to familial cutaneous melanoma, pancreatic cancer, susceptibility to, 5, leukemia, acute myeloid, susceptibility to, diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, glioma susceptibility, hemangioma, capillary infantile, susceptibility to, CDH1-related diffuse gastric and lobular breast cancer syndrome, NTHL1-deficiency tumor predisposition syndrome, SAMD9-related spectrum and myeloid neoplasm risk, neuroblastoma, susceptibility to, 2, BARD1-related cancer predisposition, BRCA1-related cancer predisposition, BRCA2-related cancer predisposition, ATM-related cancer predisposition, CHEK2-related cancer predisposition, PALB2-related cancer predisposition, RAD51C-related cancer predisposition, RAD51D-related cancer predisposition, Li-fraumeni-like syndrome, breast cancer, familial, susceptibility to, 1, breast cancer, familial, susceptibility to, 2, breast cancer, familial, susceptibility to, 3, colorectal cancer, susceptibility to, 4, colorectal cancer, susceptibility to, on chromosome 15, ovarian cancer, familial, susceptibility to, 1, ovarian cancer, familial, susceptibility to, 2, ovarian cancer, familial, susceptibility to, 3, inherited hematologic cancer-predisposing syndrome, mosaic neurofibromatosis/schwannomatosis, tumor predisposition syndrome 2, prostate cancer, hereditary, X-linked 3, follicular lymphoma, susceptibility to, GPR161-related medulloblastoma predisposition, SAMD9L-related spectrum and myeloid neoplasm risk, HAVCR2-related cancer predisposition, EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

6 retrieved; paginated sample, class counts are floors:

3 conflicting classifications of pathogenicity, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3574998	NM_001982.4(ERBB3):c.83-2A>G	ERBB3	Likely pathogenic	criteria provided, single submitter
3574999	NM_001982.4(ERBB3):c.237G>A (p.Trp79Ter)	ERBB3	Likely pathogenic	criteria provided, single submitter
3575000	NM_001982.4(ERBB3):c.3223del (p.Ser1075fs)	ERBB3	Likely pathogenic	criteria provided, single submitter
1163537	NM_001982.4(ERBB3):c.2993A>G (p.Lys998Arg)	ERBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
253223	NM_001982.4(ERBB3):c.4009G>A (p.Ala1337Thr)	ERBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
806898	NM_001982.4(ERBB3):c.89C>T (p.Pro30Leu)	ERBB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ERBB3	Orphanet:137776	Lethal congenital contracture syndrome type 2
ERBB3	Orphanet:388	Hirschsprung disease

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ERBB3	HGNC:3431	ENSG00000065361	P21860	Receptor tyrosine-protein kinase erbB-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ERBB3	Receptor tyrosine-protein kinase erbB-3	Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ERBB3	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal root ganglion	1
jejunal mucosa	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ERBB3	274	broad	marker	trigeminal ganglion, jejunal mucosa, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ERBB3	4,511

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ERBB3	P21860	23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
GRB7 events in ERBB2 signaling	1	1903.3×	0.004	ERBB3
Downregulation of ERBB2:ERBB3 signaling	1	815.7×	0.004	ERBB3
ERBB2 Activates PTK6 Signaling	1	815.7×	0.004	ERBB3
ERBB2 Regulates Cell Motility	1	713.8×	0.004	ERBB3
PI3K events in ERBB2 signaling	1	671.8×	0.004	ERBB3
SHC1 events in ERBB2 signaling	1	475.8×	0.004	ERBB3
Signaling by ERBB2 TMD/JMD mutants	1	475.8×	0.004	ERBB3
Signaling by ERBB2 KD Mutants	1	423.0×	0.004	ERBB3
Downregulation of ERBB2 signaling	1	380.7×	0.004	ERBB3
Signaling by ERBB2	1	346.1×	0.004	ERBB3
Signaling by ERBB4	1	271.9×	0.005	ERBB3
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.010	ERBB3
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.012	ERBB3
PIP3 activates AKT signaling	1	66.8×	0.016	ERBB3
RAF/MAP kinase cascade	1	61.1×	0.016	ERBB3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of cardiac muscle tissue development	1	8426.0×	0.003	ERBB3
cranial nerve development	1	5617.3×	0.003	ERBB3
negative regulation of secretion	1	3370.4×	0.003	ERBB3
Schwann cell differentiation	1	2407.4×	0.003	ERBB3
ERBB2-ERBB3 signaling pathway	1	1685.2×	0.003	ERBB3
negative regulation of motor neuron apoptotic process	1	1532.0×	0.003	ERBB3
endocardial cushion development	1	1404.3×	0.003	ERBB3
motor neuron apoptotic process	1	1123.5×	0.003	ERBB3
Schwann cell development	1	1053.2×	0.003	ERBB3
positive regulation of calcineurin-NFAT signaling cascade	1	802.5×	0.004	ERBB3
peripheral nervous system development	1	581.1×	0.005	ERBB3
extrinsic apoptotic signaling pathway in absence of ligand	1	468.1×	0.005	ERBB3
negative regulation of cell adhesion	1	383.0×	0.006	ERBB3
negative regulation of signal transduction	1	374.5×	0.006	ERBB3
myelination	1	251.5×	0.007	ERBB3
epidermal growth factor receptor signaling pathway	1	247.8×	0.007	ERBB3
positive regulation of epithelial cell proliferation	1	244.2×	0.007	ERBB3
wound healing	1	227.7×	0.007	ERBB3
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	210.7×	0.007	ERBB3
neuron apoptotic process	1	185.2×	0.008	ERBB3
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.008	ERBB3
regulation of cell population proliferation	1	115.4×	0.012	ERBB3
negative regulation of neuron apoptotic process	1	110.9×	0.012	ERBB3
neuron differentiation	1	100.3×	0.012	ERBB3
positive regulation of MAPK cascade	1	80.6×	0.014	ERBB3
heart development	1	78.8×	0.014	ERBB3
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.014	ERBB3
positive regulation of gene expression	1	38.7×	0.028	ERBB3
negative regulation of apoptotic process	1	34.8×	0.030	ERBB3
signal transduction	1	16.1×	0.062	ERBB3

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ERBB3	MOBOCERTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ERBB3	23	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOBOCERTINIB	4	ERBB3
AFATINIB	4	ERBB3
NERATINIB	4	ERBB3
VANDETANIB	4	ERBB3
BOSUTINIB	4	ERBB3
OSIMERTINIB	4	ERBB3
DASATINIB	4	ERBB3
ERLOTINIB	4	ERBB3
LAPATINIB	4	ERBB3
GEFITINIB	4	ERBB3
CANERTINIB	3	ERBB3
ROCILETINIB	3	ERBB3
ALVOCIDIB	3	ERBB3
CEDIRANIB	3	ERBB3
CANERTINIB DIHYDROCHLORIDE	3	ERBB3
LESTAURTINIB	3	ERBB3
AEE-788	2	ERBB3
FORETINIB	2	ERBB3
SAPITINIB	2	ERBB3
PF-06459988	2	ERBB3
MAVELERTINIB	2	ERBB3
TOZASERTIB	2	ERBB3
TAK-285	1	ERBB3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ERBB3	169	Binding:169

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERBB3	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ERBB3	169

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

23 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MOBOCERTINIB	4	ERBB3
AFATINIB	4	ERBB3
NERATINIB	4	ERBB3
VANDETANIB	4	ERBB3
BOSUTINIB	4	ERBB3
OSIMERTINIB	4	ERBB3
DASATINIB	4	ERBB3
ERLOTINIB	4	ERBB3
LAPATINIB	4	ERBB3
GEFITINIB	4	ERBB3
CANERTINIB	3	ERBB3
ROCILETINIB	3	ERBB3
ALVOCIDIB	3	ERBB3
CEDIRANIB	3	ERBB3
CANERTINIB DIHYDROCHLORIDE	3	ERBB3
LESTAURTINIB	3	ERBB3
AEE-788	2	ERBB3
FORETINIB	2	ERBB3
SAPITINIB	2	ERBB3
PF-06459988	2	ERBB3
MAVELERTINIB	2	ERBB3
TOZASERTIB	2	ERBB3
TAK-285	1	ERBB3

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ERBB3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.