Schizophrenia 4

Summary

Schizophrenia 4 (MONDO:0010943) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 149

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	schizophrenia 4
Mondo ID	MONDO:0010943
OMIM	600850
DOID	DOID:0070080
UMLS	C1833247
MedGen	371517
Is cancer (heuristic)	no

Also known as: schizophrenia 4 · schizophrenia type 4 · schizophrenia, susceptibility to, 4 · SCZD4

Data availability: 149 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › schizophrenia, susceptibility to › schizophrenia 4

Related subtypes (5): schizophrenia 6, 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

149 retrieved; paginated sample, class counts are floors:

98 uncertain significance, 14 likely benign, 14 conflicting classifications of pathogenicity, 8 benign/likely benign, 8 likely pathogenic, 4 benign, 1 pathogenic, 1 pathogenic/likely pathogenic, 1 pathogenic; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
4005	NC_000022.11:g.(?18906222)(18936553_?)del	DGCR6	Pathogenic; risk factor	no assertion criteria provided
1179113	GRCh37/hg19 22q11.21(chr22:18900294-18923806)	PRODH	Pathogenic	no assertion criteria provided
2916786	NM_016335.6(PRODH):c.175C>T (p.Gln59Ter)	PRODH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179165	GRCh37/hg19 22q11.21(chr22:18900895-18923882)	PRODH	Likely pathogenic	no assertion criteria provided
2201654	NM_016335.6(PRODH):c.1104+2T>C	PRODH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3587798	NM_016335.6(PRODH):c.1252-1G>A	PRODH	Likely pathogenic	criteria provided, single submitter
3587800	NM_016335.6(PRODH):c.1251+2C>T	PRODH	Likely pathogenic	criteria provided, single submitter
3587804	NM_016335.6(PRODH):c.1177_1183del (p.Leu393fs)	PRODH	Likely pathogenic	criteria provided, single submitter
3587838	NM_016335.6(PRODH):c.148_157del (p.Val50fs)	PRODH	Likely pathogenic	criteria provided, single submitter
3587846	NM_016335.6(PRODH):c.2T>G (p.Met1Arg)	PRODH	Likely pathogenic	criteria provided, single submitter
3587847	NM_016335.6(PRODH):c.1A>C (p.Met1Leu)	PRODH	Likely pathogenic	criteria provided, single submitter
1214571	NM_016335.6(PRODH):c.1729C>T (p.Arg577Trp)	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1303133	NM_016335.6(PRODH):c.1576C>T (p.Gln526Ter)	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1466893	NM_016335.6(PRODH):c.930-1G>C	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1996989	NM_016335.6(PRODH):c.1105-14C>A	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2897986	NM_016335.6(PRODH):c.930-14G>A	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3587822	NM_016335.6(PRODH):c.654C>T (p.Cys218=)	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4006	NM_016335.6(PRODH):c.1357C>T (p.Arg453Cys)	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4007	NM_016335.6(PRODH):c.865T>A (p.Leu289Met)	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4008	NM_016335.6(PRODH):c.1322T>C (p.Leu441Pro)	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4009	NM_016335.6(PRODH):c.1363G>T (p.Ala455Ser)	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4011	NM_016335.6(PRODH):c.1292G>A (p.Arg431His)	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4013	NM_016335.6(PRODH):c.1397C>T (p.Thr466Met)	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
522067	NM_016335.6(PRODH):c.1652A>C (p.Tyr551Ser)	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
702852	NM_016335.6(PRODH):c.1217C>T (p.Pro406Leu)	PRODH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1415486	NM_016335.6(PRODH):c.1A>G (p.Met1Val)	HSERVPRODH	Uncertain significance	criteria provided, multiple submitters, no conflicts
1000921	NM_016335.6(PRODH):c.1295G>A (p.Arg432His)	PRODH	Uncertain significance	criteria provided, multiple submitters, no conflicts
1016144	NM_016335.6(PRODH):c.1772G>A (p.Arg591Gln)	PRODH	Uncertain significance	criteria provided, multiple submitters, no conflicts
1036595	NM_016335.6(PRODH):c.1763G>A (p.Arg588Lys)	PRODH	Uncertain significance	criteria provided, multiple submitters, no conflicts
1045280	NM_016335.6(PRODH):c.392G>A (p.Arg131Gln)	PRODH	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRODH	Orphanet:419	Hyperprolinemia type 1

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DGCR6	HGNC:2846	ENSG00000183628	Q14129	Protein DGCR6	clinvar
PRODH	HGNC:9453	ENSG00000100033	O43272	Proline dehydrogenase 1, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DGCR6	Protein DGCR6	May play a role in neural crest cell migration into the third and fourth pharyngeal pouches.
PRODH	Proline dehydrogenase 1, mitochondrial	Converts proline to delta-1-pyrroline-5-carboxylate.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DGCR6	Other/Unknown	no		Gonadal
PRODH	Enzyme (other)	yes	1.5.5.2	Proline_DH_dom, Proline_oxidase, FAD-linked_oxidoreductase-like

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
hindlimb stylopod muscle	1
skeletal muscle tissue	1
skin of abdomen	1
skin of leg	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DGCR6	134	ubiquitous	marker	skeletal muscle tissue, hindlimb stylopod muscle, gastrocnemius
PRODH	135	broad	marker	skin of leg, zone of skin, skin of abdomen

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRODH	3,653
DGCR6	581

Intra-cohort edges

A	B	Sources
DGCR6	PRODH	string_interaction

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DGCR6	Q14129	86.83
PRODH	O43272	85.29

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Proline catabolism	1	3806.7×	3e-04	PRODH

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
L-proline metabolic process	1	2808.7×	9e-04	PRODH
obsolete L-proline catabolic process to L-glutamate	1	2808.7×	9e-04	PRODH
L-proline catabolic process	1	2106.5×	9e-04	PRODH
trans-4-hydroxy-L-proline catabolic process	1	1685.2×	9e-04	PRODH
regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	1	1685.2×	9e-04	PRODH
intrinsic apoptotic signaling pathway in response to oxidative stress	1	421.3×	0.003	PRODH
animal organ morphogenesis	1	95.8×	0.012	DGCR6
cell adhesion	1	18.7×	0.053	DGCR6

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
DGCR6	0	0
PRODH	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRODH	1.5.5.2, 1.5.99.B2	proline dehydrogenase,

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	0
D	Druggable family + AlphaFold only, no drug	1	PRODH
E	Difficult family or no structure, no drug	1	DGCR6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DGCR6	0	—
PRODH	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.