Myopia, high, with cataract and vitreoretinal degeneration

Summary

Myopia, high, with cataract and vitreoretinal degeneration (MONDO:0013670) is a disease caused by P3H2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: P3H2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopia, high, with cataract and vitreoretinal degeneration
Mondo ID	MONDO:0013670
OMIM	614292
UMLS	C3280346
MedGen	481976
GARD	0018197
Is cancer (heuristic)	no

Also known as: MCVD · myopia, high, with cataract and vitreoretinal degeneration

Data availability: 19 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › myopia › myopia, high, with cataract and vitreoretinal degeneration

Related subtypes (29): degenerative myopia, myopia 2, autosomal dominant, myopia 18, autosomal recessive, myopia 13, X-linked, myopia 1, X-linked, myopia 3, autosomal dominant, myopia 17, autosomal dominant, myopia 5, autosomal dominant, myopia 6, myopia 7, myopia 8, myopia 9, myopia 10, myopia 11, autosomal dominant, myopia 12, autosomal dominant, myopia 14, myopia 16, autosomal dominant, myopia 15, autosomal dominant, schizophrenia 16, myopia 19, autosomal dominant, myopia 20, autosomal dominant, myopia 21, autosomal dominant, myopia 22, autosomal dominant, myopia 23, autosomal recessive, myopia 24, autosomal dominant, myopia 25, autosomal dominant, myopia 28, autosomal recessive, myopia 27, myopia 26, X-linked, female-limited

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

19 retrieved; paginated sample, class counts are floors:

5 benign, 5 pathogenic, 3 likely pathogenic, 2 uncertain significance, 2 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1332864	NM_018192.4(P3H2):c.1782G>A (p.Trp594Ter)	P3H2	Pathogenic	criteria provided, single submitter
1455362	NM_018192.4(P3H2):c.1309C>T (p.Arg437Ter)	P3H2	Pathogenic	criteria provided, multiple submitters, no conflicts
162462	NM_018192.4(P3H2):c.556C>T (p.Gln186Ter)	P3H2	Pathogenic	criteria provided, single submitter
225632	NM_018192.4(P3H2):c.297del (p.Gly100fs)	P3H2	Pathogenic	criteria provided, multiple submitters, no conflicts
30822	NM_018192.4(P3H2):c.1523G>T (p.Gly508Val)	P3H2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3776034	NM_018192.4(P3H2):c.797_809del (p.Lys266fs)	P3H2	Pathogenic	criteria provided, single submitter
812364	NM_018192.4(P3H2):c.1213C>T (p.Arg405Ter)	P3H2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2690665	NM_018192.4(P3H2):c.297dup (p.Gly100fs)	P3H2	Likely pathogenic	criteria provided, single submitter
3382489	NM_018192.4(P3H2):c.124C>T (p.Gln42Ter)	P3H2	Likely pathogenic	criteria provided, single submitter
635546	NM_018192.4(P3H2):c.679G>T (p.Glu227Ter)	P3H2	Likely pathogenic	no assertion criteria provided
547920	NM_018192.4(P3H2):c.555G>T (p.Gln185His)	P3H2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1038309	NM_018192.4(P3H2):c.467G>C (p.Arg156Pro)	P3H2	Uncertain significance	criteria provided, multiple submitters, no conflicts
844247	NM_018192.4(P3H2):c.101TGGAGC[3] (p.34LE[3])	P3H2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1164953	NM_018192.4(P3H2):c.634-17C>T	P3H2	Benign	criteria provided, multiple submitters, no conflicts
1168224	NM_018192.4(P3H2):c.634-18C>T	P3H2	Benign	criteria provided, multiple submitters, no conflicts
1170223	NM_018192.4(P3H2):c.1189-17del	P3H2	Benign	criteria provided, multiple submitters, no conflicts
677171	NM_018192.4(P3H2):c.507A>G (p.Glu169=)	P3H2	Benign	criteria provided, multiple submitters, no conflicts
677218	NM_018192.4(P3H2):c.696C>T (p.His232=)	P3H2	Benign	criteria provided, multiple submitters, no conflicts
767944	NM_018192.4(P3H2):c.972A>G (p.Lys324=)	P3H2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
P3H2	Strong	Autosomal recessive	myopia, high, with cataract and vitreoretinal degeneration	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
P3H2	Orphanet:98619	Rare isolated myopia

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
P3H2	HGNC:19317	ENSG00000090530	Q8IVL5	Prolyl 3-hydroxylase 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
P3H2	Prolyl 3-hydroxylase 2	Prolyl 3-hydroxylase that catalyzes the post-translational formation of 3-hydroxyproline on collagens.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
P3H2	Enzyme (other)	yes	1.14.11.7	Oxoglu/Fe-dep_dioxygenase_dom, Pro_4_hyd_alph, TPR-like_helical_dom_sf

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
adrenal tissue	1
cartilage tissue	1
metanephros cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
P3H2	215	ubiquitous	marker	adrenal tissue, cartilage tissue, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
P3H2	895

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
P3H2	Q8IVL5	83.62

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Collagen biosynthesis and modifying enzymes	1	170.4×	0.006	P3H2

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
peptidyl-proline hydroxylation	1	8426.0×	4e-04	P3H2
collagen metabolic process	1	1053.2×	0.001	P3H2
negative regulation of cell population proliferation	1	42.1×	0.024	P3H2

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
P3H2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
P3H2	1.14.11.7	procollagen-proline 3-dioxygenase

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	0
D	Druggable family + AlphaFold only, no drug	1	P3H2
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)
P3H2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.