Myopia 25, autosomal dominant

Summary

Myopia 25, autosomal dominant (MONDO:0014982) is a disease with 6 cohort genes.

At a glance

• Cohort genes: 6
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopia 25, autosomal dominant
Mondo ID	MONDO:0014982
OMIM	617238
UMLS	C4310655
MedGen	934622
Is cancer (heuristic)	no

Also known as: myopia (disease) caused by mutation in P4HA2 · myopia 25, autosomal dominant · myopia 25, autosomal dominant; MYP25 · MYP25 · P4HA2 myopia (disease)

Data availability: 17 ClinVar variants · 2 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 25, autosomal dominant

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, high, with cataract and vitreoretinal degeneration, myopia 22, autosomal dominant, myopia 23, autosomal recessive, myopia 24, 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

17 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 4 pathogenic, 3 likely pathogenic, 2 conflicting classifications of pathogenicity, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
372166	NM_001017974.2(P4HA2):c.419A>G (p.Gln140Arg)	P4HA2	Pathogenic	no assertion criteria provided
372167	NM_001365677.2(P4HA2):c.1352_1353del (p.Val451fs)	P4HA2	Pathogenic	no assertion criteria provided
91389	NM_001034853.2(RPGR):c.2405_2406del (p.Glu802fs)	RPGR	Pathogenic	reviewed by expert panel
4082196	NM_152564.5(VPS13B):c.2555C>G (p.Ser852Ter)	VPS13B	Pathogenic	criteria provided, multiple submitters, no conflicts
4082191	NM_001017974.2(P4HA2):c.601G>C (p.Glu201Gln)	P4HA2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4082194	NM_001017974.2(P4HA2):c.751G>A (p.Glu251Lys)	P4HA2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4082195	NM_001330360.2(POLA1):c.2121T>G (p.Ile707Met)	POLA1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
65712	NM_014336.5(AIPL1):c.905G>T (p.Arg302Leu)	AIPL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
964375	NM_004385.5(VCAN):c.3373C>T (p.Arg1125Cys)	VCAN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2377982	NM_001017974.2(P4HA2):c.1129G>T (p.Ala377Ser)	P4HA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2434538	NM_001017974.2(P4HA2):c.782C>A (p.Thr261Lys)	P4HA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3364271	NM_001017974.2(P4HA2):c.1440A>G (p.Thr480=)	P4HA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
372165	NM_001017974.2(P4HA2):c.871G>A (p.Glu291Lys)	P4HA2	Uncertain significance	criteria provided, single submitter
3891890	NM_001017974.2(P4HA2):c.1034T>C (p.Met345Thr)	P4HA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891891	NM_001017974.2(P4HA2):c.1589C>G (p.Thr530Arg)	P4HA2	Uncertain significance	criteria provided, single submitter
732289	NM_001017974.2(P4HA2):c.654C>G (p.Phe218Leu)	P4HA2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
791578	NM_001017974.2(P4HA2):c.226G>T (p.Ala76Ser)	P4HA2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 12 · 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
P4HA2	Strong	Autosomal dominant	myopia	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
P4HA2	Orphanet:397	Giant cell arteritis
RPGR	Orphanet:1872	Cone rod dystrophy
RPGR	Orphanet:244	Primary ciliary dyskinesia
RPGR	Orphanet:247522	Primary ciliary dyskinesia-retinitis pigmentosa syndrome
RPGR	Orphanet:49382	Achromatopsia
RPGR	Orphanet:791	Retinitis pigmentosa
VPS13B	Orphanet:193	Cohen syndrome
VCAN	Orphanet:898	Wagner disease
AIPL1	Orphanet:1872	Cone rod dystrophy
AIPL1	Orphanet:65	Leber congenital amaurosis
POLA1	Orphanet:163976	X-linked intellectual disability, Van Esch type
POLA1	Orphanet:85453	X-linked reticulate pigmentary disorder

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
P4HA2	HGNC:8547	ENSG00000072682	O15460	Prolyl 4-hydroxylase subunit alpha-2	gencc,clinvar
RPGR	HGNC:10295	ENSG00000156313	Q92834	X-linked retinitis pigmentosa GTPase regulator	clinvar
VPS13B	HGNC:2183	ENSG00000132549	Q7Z7G8	Intermembrane lipid transfer protein VPS13B	clinvar
VCAN	HGNC:2464	ENSG00000038427	P13611	Versican core protein	clinvar
AIPL1	HGNC:359	ENSG00000129221	Q9NZN9	Aryl-hydrocarbon-interacting protein-like 1	clinvar
POLA1	HGNC:9173	ENSG00000101868	P09884	DNA polymerase alpha catalytic subunit	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
P4HA2	Prolyl 4-hydroxylase subunit alpha-2	Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
RPGR	X-linked retinitis pigmentosa GTPase regulator	Acts as a guanine-nucleotide releasing factor (GEF) for RAB8A and RAB37 by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP.
VPS13B	Intermembrane lipid transfer protein VPS13B	Mediates the transfer of lipids between membranes at organelle contact sites.
VCAN	Versican core protein	May play a role in intercellular signaling and in connecting cells with the extracellular matrix.
AIPL1	Aryl-hydrocarbon-interacting protein-like 1	May be important in protein trafficking and/or protein folding and stabilization.
POLA1	DNA polymerase alpha catalytic subunit	Catalytic subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.33

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
Complement	1	44.7×	0.089
Enzyme (other)	1	2.0×	0.719
Transcription factor	1	1.4×	0.719
Other/Unknown	3	0.9×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
P4HA2	Enzyme (other)	yes	1.14.11.2	Oxoglu/Fe-dep_dioxygenase_dom, Pro_4_hyd_alph, TPR-like_helical_dom_sf
RPGR	Other/Unknown	no		Reg_chr_condens, RCC1/BLIP-II, Signaling_Regulatory_Domain
VPS13B	Other/Unknown	no		VPS13_VAB, VPS13_N, VPS13B
VCAN	Complement	yes		EGF-type_Asp/Asn_hydroxyl_site, Sushi_SCR_CCP_dom, Link_dom
AIPL1	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, AIP/AIPL1/TTC9
POLA1	Transcription factor	no	2.7.7.102	DNA-dir_DNA_pol_B_exonuc, DNA-dir_DNA_pol_B_multi_dom, DNA-dir_DNA_pol_B

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	2
sural nerve	2
body of pancreas	1
stromal cell of endometrium	1
tibia	1
right uterine tube	1
sperm	1
nipple	1
leukocyte	1
monocyte	1
mononuclear cell	1
buccal mucosa cell	1
pancreatic ductal cell	1
tendon of biceps brachii	1
calcaneal tendon	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
P4HA2	274	ubiquitous	marker	stromal cell of endometrium, tibia, body of pancreas
RPGR	281	ubiquitous	marker	sperm, bronchial epithelial cell, right uterine tube
VPS13B	291	ubiquitous	marker	sural nerve, nipple, bronchial epithelial cell
VCAN	293	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
AIPL1	62	tissue_specific	marker	buccal mucosa cell, pancreatic ductal cell, tendon of biceps brachii
POLA1	231	ubiquitous	marker	ventricular zone, sural nerve, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POLA1	3,189
VCAN	2,806
P4HA2	2,423
RPGR	2,231
VPS13B	1,950
AIPL1	891

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
POLA1	P09884	21
P4HA2	O15460	7
AIPL1	Q9NZN9	6
RPGR	Q92834	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
VPS13B	Q7Z7G8
VCAN	P13611

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 6 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective CHST3 causes SEDCJD	1	475.8×	0.009	VCAN
Defective CHST14 causes EDS, musculocontractural type	1	475.8×	0.009	VCAN
Defective CHSY1 causes TPBS	1	475.8×	0.009	VCAN
DNA replication initiation	1	475.8×	0.009	POLA1
Processive synthesis on the lagging strand	1	380.7×	0.009	POLA1
DS-GAG biosynthesis	1	317.2×	0.009	VCAN
Inhibition of replication initiation of damaged DNA by RB1/E2F1	1	271.9×	0.009	POLA1
Telomere C-strand synthesis initiation	1	271.9×	0.009	POLA1
Polymerase switching	1	271.9×	0.009	POLA1
Removal of the Flap Intermediate	1	271.9×	0.009	POLA1
Defective B4GALT7 causes EDS, progeroid type	1	190.3×	0.009	VCAN
Defective B3GAT3 causes JDSSDHD	1	190.3×	0.009	VCAN
Defective B3GALT6 causes EDSP2 and SEMDJL1	1	190.3×	0.009	VCAN
CS-GAG biosynthesis	1	181.3×	0.009	VCAN
CS/DS degradation	1	181.3×	0.009	VCAN
Polymerase switching on the C-strand of the telomere	1	141.0×	0.011	POLA1
Glycosaminoglycan-protein linkage region biosynthesis	1	131.3×	0.011	VCAN
G1/S-Specific Transcription	1	119.0×	0.012	POLA1
Activation of the pre-replicative complex	1	108.8×	0.012	POLA1
Maturation of DENV proteins	1	70.5×	0.018	P4HA2
Collagen biosynthesis and modifying enzymes	1	56.8×	0.021	P4HA2
Defective pyroptosis	1	52.1×	0.022	POLA1
ECM proteoglycans	1	50.1×	0.022	VCAN
Post-translational protein phosphorylation	1	33.4×	0.031	VCAN
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	28.8×	0.034	VCAN

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
slow endocytic recycling	1	1685.2×	0.009	VPS13B
lagging strand elongation	1	1123.5×	0.009	POLA1
protein farnesylation	1	1123.5×	0.009	AIPL1
leading strand elongation	1	842.6×	0.009	POLA1
protein localization to non-motile cilium	1	842.6×	0.009	RPGR
Golgi reassembly	1	674.1×	0.009	VPS13B
DNA replication, synthesis of primer	1	561.7×	0.009	POLA1
mitotic DNA replication initiation	1	561.7×	0.009	POLA1
central nervous system development	2	46.2×	0.009	VPS13B, VCAN
visual perception	2	31.8×	0.009	RPGR, AIPL1
maintenance of lens transparency	1	421.3×	0.009	VPS13B
head morphogenesis	1	421.3×	0.009	VPS13B
DNA strand elongation involved in DNA replication	1	374.5×	0.009	POLA1
cell recognition	1	374.5×	0.009	VCAN
regulation of opsin-mediated signaling pathway	1	337.0×	0.009	AIPL1
regulation of type I interferon production	1	337.0×	0.009	POLA1
glial cell migration	1	280.9×	0.010	VCAN
phototransduction, visible light	1	259.3×	0.010	AIPL1
retina homeostasis	1	224.7×	0.011	AIPL1
DNA synthesis involved in DNA repair	1	187.2×	0.013	POLA1
eye photoreceptor cell development	1	168.5×	0.014	RPGR
DNA replication initiation	1	124.8×	0.017	POLA1
dentate gyrus development	1	124.8×	0.017	VPS13B
intraciliary transport	1	112.3×	0.018	RPGR
acrosome assembly	1	91.1×	0.021	VPS13B
double-strand break repair via nonhomologous end joining	1	84.3×	0.022	POLA1
adipose tissue development	1	80.2×	0.022	VPS13B
social behavior	1	54.4×	0.031	VPS13B
lipid transport	1	52.7×	0.031	VPS13B
positive regulation of autophagy	1	41.6×	0.038	RPGR

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 3 of 6 evidence-associated genes (50%) 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
POLA1	RUCAPARIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
POLA1	3	4
P4HA2	0	0
RPGR	0	0
VPS13B	0	0
VCAN	0	0
AIPL1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RUCAPARIB	4	POLA1
ADEFOVIR DIPIVOXIL	4	POLA1
RESVERATROL	3	POLA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
POLA1	73	Binding:64, ADMET:5, Functional:4
P4HA2	1	Binding:1
AIPL1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
P4HA2	1.14.11.2	procollagen-proline 4-dioxygenase
POLA1	2.7.7.102	DNA primase AEP

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

3 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)
RUCAPARIB	4	POLA1
ADEFOVIR DIPIVOXIL	4	POLA1
RESVERATROL	3	POLA1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	POLA1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	P4HA2
D	Druggable family + AlphaFold only, no drug	1	VCAN
E	Difficult family or no structure, no drug	3	RPGR, VPS13B, AIPL1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
P4HA2	1	—
RPGR	0	—
VPS13B	0	—
VCAN	0	—
AIPL1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.