Schizophrenia 6

Summary

Schizophrenia 6 (MONDO:0011280) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	schizophrenia 6
Mondo ID	MONDO:0011280
OMIM	603013
DOID	DOID:0070082
UMLS	C1864275
MedGen	350380
Is cancer (heuristic)	no

Also known as: schizophrenia 6 · schizophrenia susceptibility locus, chromosome 8P-related · SCZD6

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

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › schizophrenia, susceptibility to › schizophrenia 6

Related subtypes (5): schizophrenia 4, schizophrenia 9, schizophrenia 14, schizophrenia 13, schizophrenia 18

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

1 retrieved; paginated sample, class counts are floors:

1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1285117	NM_013964.5(NRG1):c.1062-5C>T	LOC126860346	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
NRG1	Limited	Autosomal recessive	schizophrenia 6	3

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
NRG1	HGNC:7997	ENSG00000157168	Q02297	Pro-neuregulin-1, membrane-bound isoform	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NRG1	Pro-neuregulin-1, membrane-bound isoform	Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NRG1	Antibody/Immunoglobulin	yes		EGF, Neuregulin_C, Ig_sub2

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
ganglionic eminence	1
oocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NRG1	209	ubiquitous	marker	ventricular zone, ganglionic eminence, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NRG1	197

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NRG1	Q02297	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. 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	NRG1
PI3K events in ERBB4 signaling	1	1038.2×	0.004	NRG1
Downregulation of ERBB2:ERBB3 signaling	1	815.7×	0.004	NRG1
ERBB2 Activates PTK6 Signaling	1	815.7×	0.004	NRG1
SHC1 events in ERBB4 signaling	1	713.8×	0.004	NRG1
ERBB2 Regulates Cell Motility	1	713.8×	0.004	NRG1
PI3K events in ERBB2 signaling	1	671.8×	0.004	NRG1
GRB2 events in ERBB2 signaling	1	634.4×	0.004	NRG1
SHC1 events in ERBB2 signaling	1	475.8×	0.004	NRG1
Long-term potentiation	1	475.8×	0.004	NRG1
Signaling by ERBB2 TMD/JMD mutants	1	475.8×	0.004	NRG1
Signaling by ERBB2 KD Mutants	1	423.0×	0.004	NRG1
Downregulation of ERBB2 signaling	1	380.7×	0.004	NRG1
Signaling by ERBB2	1	346.1×	0.004	NRG1
Nuclear signaling by ERBB4	1	346.1×	0.004	NRG1
Signaling by ERBB4	1	271.9×	0.005	NRG1
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.009	NRG1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.011	NRG1
PIP3 activates AKT signaling	1	66.8×	0.016	NRG1
RAF/MAP kinase cascade	1	61.1×	0.016	NRG1

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
ERBB3 signaling pathway	1	8426.0×	0.002	NRG1
positive regulation of peptidyl-tyrosine autophosphorylation	1	8426.0×	0.002	NRG1
ERBB signaling pathway	1	3370.4×	0.002	NRG1
negative regulation of secretion	1	3370.4×	0.002	NRG1
ERBB4 signaling pathway	1	2808.7×	0.002	NRG1
ERBB2-ERBB4 signaling pathway	1	2808.7×	0.002	NRG1
positive regulation of striated muscle cell differentiation	1	2808.7×	0.002	NRG1
endocardial cell differentiation	1	2808.7×	0.002	NRG1
ERBB4-ERBB4 signaling pathway	1	2407.4×	0.002	NRG1
ventricular cardiac muscle cell differentiation	1	2407.4×	0.002	NRG1
activation of protein kinase B activity	1	1872.4×	0.002	NRG1
ERBB2 signaling pathway	1	1872.4×	0.002	NRG1
ERBB2-ERBB3 signaling pathway	1	1685.2×	0.002	NRG1
cardiac muscle cell myoblast differentiation	1	1404.3×	0.002	NRG1
ventricular trabecula myocardium morphogenesis	1	1053.2×	0.002	NRG1
cell communication	1	842.6×	0.003	NRG1
neural crest cell development	1	802.5×	0.003	NRG1
cardiac muscle cell differentiation	1	674.1×	0.003	NRG1
mammary gland development	1	648.1×	0.003	NRG1
positive regulation of cardiac muscle cell proliferation	1	624.1×	0.003	NRG1
regulation of postsynaptic neurotransmitter receptor internalization	1	624.1×	0.003	NRG1
peripheral nervous system development	1	581.1×	0.003	NRG1
negative regulation of cardiac muscle cell apoptotic process	1	543.6×	0.003	NRG1
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	411.0×	0.004	NRG1
positive regulation of protein-containing complex assembly	1	337.0×	0.004	NRG1
positive regulation of cell adhesion	1	271.8×	0.005	NRG1
wound healing	1	227.7×	0.006	NRG1
positive regulation of cell growth	1	183.2×	0.007	NRG1
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.007	NRG1
cell population proliferation	1	102.8×	0.012	NRG1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NRG1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	NRG1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NRG1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.