Visceral neuropathy, familial, 2, autosomal recessive

Summary

Visceral neuropathy, familial, 2, autosomal recessive (MONDO:0030399) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 42

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	visceral neuropathy, familial, 2, autosomal recessive
Mondo ID	MONDO:0030399
OMIM	619465
UMLS	C5561950
MedGen	1794160
Is cancer (heuristic)	no

Also known as: VSCN2

Data availability: 42 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › visceral neuropathy, familial › visceral neuropathy, familial, 2, autosomal recessive

Related subtypes (1): visceral neuropathy, familial, 1, autosomal recessive

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

42 retrieved; paginated sample, class counts are floors:

35 uncertain significance, 6 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1188812	NM_004448.4(ERBB2):c.2129C>T (p.Ala710Val)	ERBB2	Pathogenic	no assertion criteria provided
1060897	NM_004448.4(ERBB2):c.3436C>T (p.Arg1146Trp)	ERBB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1587981	NM_004448.4(ERBB2):c.1179G>A (p.Gln393=)	ERBB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2171330	NM_004448.4(ERBB2):c.3573G>A (p.Val1191=)	ERBB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2428038	NM_004448.4(ERBB2):c.1513+17A>G	ERBB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2721202	NM_004448.4(ERBB2):c.3674_3679del (p.Gln1225_Asp1226del)	ERBB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
964033	NM_004448.4(ERBB2):c.1294C>T (p.Arg432Trp)	ERBB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
134071	NM_004448.4(ERBB2):c.1466C>T (p.Pro489Leu)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
134073	NM_004448.4(ERBB2):c.1793C>A (p.Ala598Asp)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
134079	NM_004448.4(ERBB2):c.3182T>C (p.Leu1061Pro)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
134091	NM_004448.4(ERBB2):c.734C>T (p.Thr245Met)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1370308	NM_004448.4(ERBB2):c.455G>C (p.Gly152Ala)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1380837	NM_004448.4(ERBB2):c.3142C>T (p.Arg1048Cys)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1424946	NM_004448.4(ERBB2):c.3166G>A (p.Gly1056Ser)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1432121	NM_004448.4(ERBB2):c.1409A>G (p.His470Arg)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1438528	NM_004448.4(ERBB2):c.608G>A (p.Arg203His)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1446943	NM_004448.4(ERBB2):c.649C>T (p.Arg217Cys)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1496387	NM_004448.4(ERBB2):c.199A>G (p.Thr67Ala)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1497000	NM_004448.4(ERBB2):c.74T>C (p.Val25Ala)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2074936	NM_004448.4(ERBB2):c.3110C>T (p.Pro1037Leu)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2097466	NM_004448.4(ERBB2):c.1556A>G (p.His519Arg)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2169611	NM_004448.4(ERBB2):c.569G>A (p.Arg190Gln)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2169773	NM_004448.4(ERBB2):c.562C>T (p.Arg188Cys)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2170431	NM_004448.4(ERBB2):c.1270G>A (p.Val424Ile)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2173210	NM_004448.4(ERBB2):c.3288G>C (p.Lys1096Asn)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2885022	NM_004448.4(ERBB2):c.1550G>A (p.Arg517Gln)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2966293	NM_004448.4(ERBB2):c.3463G>T (p.Gly1155Cys)	ERBB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3581926	NM_004448.4(ERBB2):c.647C>T (p.Thr216Met)	ERBB2	Uncertain significance	criteria provided, single submitter
3581927	NM_004448.4(ERBB2):c.655G>C (p.Val219Leu)	ERBB2	Uncertain significance	criteria provided, single submitter
3581929	NM_004448.4(ERBB2):c.818C>T (p.Thr273Ile)	ERBB2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ERBB2	Limited	Unknown	visceral neuropathy, familial, 2, autosomal recessive	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ERBB2	Orphanet:213726	Serous carcinoma of the corpus uteri
ERBB2	Orphanet:2800	Extramammary Paget disease
ERBB2	Orphanet:388	Hirschsprung disease
ERBB2	Orphanet:99976	Adenocarcinoma of the oesophagus and oesophagogastric junction

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
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ERBB2	Receptor tyrosine-protein kinase erbB-2	Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.

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)
ERBB2	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
lower esophagus mucosa	1
right uterine tube	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ERBB2	9,659

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ERBB2	P04626	63

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 33. 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
PLCG1 events in ERBB2 signaling	1	2855.0×	0.001	ERBB2
Drug-mediated inhibition of ERBB2 signaling	1	2855.0×	0.001	ERBB2
Resistance of ERBB2 KD mutants to trastuzumab	1	2855.0×	0.001	ERBB2
Resistance of ERBB2 KD mutants to sapitinib	1	2855.0×	0.001	ERBB2
Resistance of ERBB2 KD mutants to tesevatinib	1	2855.0×	0.001	ERBB2
Resistance of ERBB2 KD mutants to neratinib	1	2855.0×	0.001	ERBB2
Resistance of ERBB2 KD mutants to osimertinib	1	2855.0×	0.001	ERBB2
Resistance of ERBB2 KD mutants to afatinib	1	2855.0×	0.001	ERBB2
Resistance of ERBB2 KD mutants to AEE788	1	2855.0×	0.001	ERBB2
Resistance of ERBB2 KD mutants to lapatinib	1	2855.0×	0.001	ERBB2
Drug resistance in ERBB2 TMD/JMD mutants	1	2855.0×	0.001	ERBB2
GRB7 events in ERBB2 signaling	1	1903.3×	0.001	ERBB2
Constitutive Signaling by Overexpressed ERBB2	1	951.7×	0.002	ERBB2
Downregulation of ERBB2:ERBB3 signaling	1	815.7×	0.002	ERBB2
ERBB2 Activates PTK6 Signaling	1	815.7×	0.002	ERBB2
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	761.3×	0.002	ERBB2
Developmental Lineage of Mammary Stem Cells	1	761.3×	0.002	ERBB2
ERBB2 Regulates Cell Motility	1	713.8×	0.002	ERBB2
PI3K events in ERBB2 signaling	1	671.8×	0.002	ERBB2
Signaling by ERBB2 ECD mutants	1	671.8×	0.002	ERBB2
GRB2 events in ERBB2 signaling	1	634.4×	0.002	ERBB2
Sema4D induced cell migration and growth-cone collapse	1	571.0×	0.003	ERBB2
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	543.8×	0.003	ERBB2
SHC1 events in ERBB2 signaling	1	475.8×	0.003	ERBB2
Signaling by ERBB2 TMD/JMD mutants	1	475.8×	0.003	ERBB2
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	456.8×	0.003	ERBB2
Signaling by ERBB2 KD Mutants	1	423.0×	0.003	ERBB2
Downregulation of ERBB2 signaling	1	380.7×	0.003	ERBB2
Signaling by ERBB2	1	346.1×	0.003	ERBB2
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.009	ERBB2

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
immature T cell proliferation in thymus	1	3370.4×	0.004	ERBB2
negative regulation of immature T cell proliferation in thymus	1	2808.7×	0.004	ERBB2
ERBB2-ERBB4 signaling pathway	1	2808.7×	0.004	ERBB2
regulation of microtubule-based process	1	1872.4×	0.004	ERBB2
ERBB2-ERBB3 signaling pathway	1	1685.2×	0.004	ERBB2
ERBB2-EGFR signaling pathway	1	1685.2×	0.004	ERBB2
enzyme-linked receptor protein signaling pathway	1	1296.3×	0.004	ERBB2
Schwann cell development	1	1053.2×	0.005	ERBB2
neurotransmitter receptor localization to postsynaptic specialization membrane	1	802.5×	0.005	ERBB2
motor neuron axon guidance	1	702.2×	0.005	ERBB2
positive regulation of MAP kinase activity	1	648.1×	0.005	ERBB2
positive regulation of transcription by RNA polymerase I	1	648.1×	0.005	ERBB2
positive regulation of Rho protein signal transduction	1	581.1×	0.005	ERBB2
regulation of ERK1 and ERK2 cascade	1	581.1×	0.005	ERBB2
positive regulation of protein targeting to membrane	1	561.7×	0.005	ERBB2
neuromuscular junction development	1	526.6×	0.005	ERBB2
peptidyl-tyrosine phosphorylation	1	421.3×	0.005	ERBB2
regulation of angiogenesis	1	421.3×	0.005	ERBB2
oligodendrocyte differentiation	1	421.3×	0.005	ERBB2
semaphorin-plexin signaling pathway	1	401.2×	0.005	ERBB2
cellular response to growth factor stimulus	1	318.0×	0.006	ERBB2
cellular response to epidermal growth factor stimulus	1	318.0×	0.006	ERBB2
positive regulation of cell adhesion	1	271.8×	0.006	ERBB2
myelination	1	251.5×	0.006	ERBB2
epidermal growth factor receptor signaling pathway	1	247.8×	0.006	ERBB2
positive regulation of epithelial cell proliferation	1	244.2×	0.006	ERBB2
wound healing	1	227.7×	0.006	ERBB2
positive regulation of translation	1	227.7×	0.006	ERBB2
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	210.7×	0.007	ERBB2
positive regulation of cell growth	1	183.2×	0.007	ERBB2

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
ERBB2	CLOTRIMAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ERBB2	83	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOTRIMAZOLE	4	ERBB2
ERLOTINIB HYDROCHLORIDE	4	ERBB2
PONATINIB	4	ERBB2
AFATINIB	4	ERBB2
LAPATINIB DITOSYLATE	4	ERBB2
SORAFENIB	4	ERBB2
NERATINIB	4	ERBB2
IBRUTINIB	4	ERBB2
AFATINIB DIMALEATE	4	ERBB2
CABOZANTINIB	4	ERBB2
DACOMITINIB	4	ERBB2
DACOMITINIB ANHYDROUS	4	ERBB2
VANDETANIB	4	ERBB2
TRIBROMSALAN	4	ERBB2
BOSUTINIB	4	ERBB2
BITHIONOL	4	ERBB2
ASTEMIZOLE	4	ERBB2
EBASTINE	4	ERBB2
OSIMERTINIB	4	ERBB2
BRIGATINIB	4	ERBB2
ACALABRUTINIB	4	ERBB2
ZANUBRUTINIB	4	ERBB2
TUCATINIB	4	ERBB2
TIRABRUTINIB	4	ERBB2
PACLITAXEL	4	ERBB2
LAZERTINIB	4	ERBB2
HEXACHLOROPHENE	4	ERBB2
DOXORUBICIN	4	ERBB2
DASATINIB	4	ERBB2
ERLOTINIB	4	ERBB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERBB2	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
ERBB2	1,221

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

30 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)
CLOTRIMAZOLE	4	ERBB2
ERLOTINIB HYDROCHLORIDE	4	ERBB2
PONATINIB	4	ERBB2
AFATINIB	4	ERBB2
LAPATINIB DITOSYLATE	4	ERBB2
SORAFENIB	4	ERBB2
NERATINIB	4	ERBB2
IBRUTINIB	4	ERBB2
AFATINIB DIMALEATE	4	ERBB2
CABOZANTINIB	4	ERBB2
DACOMITINIB	4	ERBB2
DACOMITINIB ANHYDROUS	4	ERBB2
VANDETANIB	4	ERBB2
TRIBROMSALAN	4	ERBB2
BOSUTINIB	4	ERBB2
BITHIONOL	4	ERBB2
ASTEMIZOLE	4	ERBB2
EBASTINE	4	ERBB2
OSIMERTINIB	4	ERBB2
BRIGATINIB	4	ERBB2
ACALABRUTINIB	4	ERBB2
ZANUBRUTINIB	4	ERBB2
TUCATINIB	4	ERBB2
TIRABRUTINIB	4	ERBB2
PACLITAXEL	4	ERBB2
LAZERTINIB	4	ERBB2
HEXACHLOROPHENE	4	ERBB2
DOXORUBICIN	4	ERBB2
DASATINIB	4	ERBB2
ERLOTINIB	4	ERBB2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ERBB2
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.