Persistent hyperplastic primary vitreous

Summary

Persistent hyperplastic primary vitreous (MONDO:0019631) is a disease with 5 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 5
• ClinVar variants: 2
• Phenotypes (HPO): 24

Clinical features

Signs & symptoms

Clinical features (HPO)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0007968	Remnants of the hyaloid vascular system	Obligate (100%)
HP:0000518	Cataract	Very frequent (80-99%)
HP:0000555	Leukocoria	Very frequent (80-99%)
HP:0000568	Microphthalmia	Very frequent (80-99%)
HP:0007663	Reduced visual acuity	Very frequent (80-99%)
HP:0007957	Corneal opacity	Very frequent (80-99%)
HP:0000519	Developmental cataract	Frequent (30-79%)
HP:0007917	Tractional retinal detachment	Frequent (30-79%)
HP:0009917	Persistent pupillary membrane	Frequent (30-79%)
HP:0012109	Angle closure glaucoma	Frequent (30-79%)
HP:0030743	Glial remnants anterior to the optic disc	Frequent (30-79%)
HP:0030744	Hyaloid vascular remnant and retrolental mass	Frequent (30-79%)
HP:0000482	Microcornea	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000557	Buphthalmos	Occasional (5-29%)
HP:0000594	Shallow anterior chamber	Occasional (5-29%)
HP:0000618	Blindness	Occasional (5-29%)
HP:0000646	Amblyopia	Occasional (5-29%)
HP:0000667	Phthisis bulbi	Occasional (5-29%)
HP:0001104	Macular hypoplasia	Occasional (5-29%)
HP:0008052	Retinal fold	Occasional (5-29%)
HP:0009926	Epiphora	Occasional (5-29%)
HP:0011885	Hemorrhage of the eye	Occasional (5-29%)
HP:0010766	Ectopic calcification	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	persistent hyperplastic primary vitreous
Mondo ID	MONDO:0019631
MeSH	D054514
OMIM	221900
Orphanet	91495
DOID	DOID:0060282
ICD-11	1011137326
NCIT	C161554
SNOMED CT	314270008
UMLS	C0266568
MedGen	120583
GARD	0016803
Is cancer (heuristic)	no

Also known as: congenital retinal detachment · ncRNA disease · non-syndromic congenital retinal non-attachment · persistent fetal vasculature syndrome · persistent foetal vasculature syndrome · PFVS · PHPV

Data availability: 2 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › vitreous body disorder › vitreous disorder › persistent hyperplastic primary vitreous

Related subtypes (3): vitreous syneresis, vitreous abscess, vitreous detachment

Subtypes (2): persistent hyperplastic primary vitreous, autosomal recessive, persistent hyperplastic primary vitreous, autosomal dominant

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
217342	NM_012064.4(MIP):c.97C>T (p.Arg33Cys)	MIP	Pathogenic	criteria provided, multiple submitters, no conflicts
374014	NM_000266.4(NDP):c.314C>T (p.Ala105Val)	NDP	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 22 · Orphanet: 16 · 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
ATOH7	Strong	Autosomal recessive	persistent hyperplastic primary vitreous, autosomal recessive	6
FZD4	Supportive	Autosomal dominant	persistent hyperplastic primary vitreous	7
NDP	Supportive	Autosomal dominant	persistent hyperplastic primary vitreous	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NDP	Orphanet:190	Coats disease
NDP	Orphanet:649	Norrie disease
NDP	Orphanet:891	Familial exudative vitreoretinopathy
NDP	Orphanet:90050	Retinopathy of prematurity
NDP	Orphanet:91495	Persistent hyperplastic primary vitreous
ATOH7	Orphanet:289499	Congenital cataract microcornea with corneal opacity
ATOH7	Orphanet:91495	Persistent hyperplastic primary vitreous
FZD4	Orphanet:891	Familial exudative vitreoretinopathy
FZD4	Orphanet:90050	Retinopathy of prematurity
FZD4	Orphanet:91495	Persistent hyperplastic primary vitreous
MIP	Orphanet:441452	Early-onset lamellar cataract
MIP	Orphanet:98985	Early-onset sutural cataract
MIP	Orphanet:98989	Cerulean cataract
MIP	Orphanet:98991	Early-onset nuclear cataract
MIP	Orphanet:98993	Early-onset posterior polar cataract
MIP	Orphanet:98994	Total early-onset cataract

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NDP	HGNC:7678	ENSG00000124479	Q00604	Norrin	gencc,clinvar
ATOH7	HGNC:13907	ENSG00000179774	Q8N100	Transcription factor ATOH7	gencc
FZD4	HGNC:4042	ENSG00000174804	Q9ULV1	Frizzled-4	gencc
TNPO1	HGNC:6401	ENSG00000083312	Q92973	Transportin-1	clinvar
MIP	HGNC:7103	ENSG00000135517	P30301	Lens fiber major intrinsic protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDP	Norrin	Activates the canonical Wnt signaling pathway through FZD4 and LRP5 coreceptor.
ATOH7	Transcription factor ATOH7	Transcription factor that binds to DNA at the consensus sequence 5’-CAG[GC]TG-3'.
FZD4	Frizzled-4	Receptor for Wnt proteins.
TNPO1	Transportin-1	Functions in nuclear protein import as nuclear transport receptor.
MIP	Lens fiber major intrinsic protein	Aquaporins form homotetrameric transmembrane channels, with each monomer independently mediating water transport across the plasma membrane along its osmotic gradient.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.2

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
GPCR	1	4.8×	0.576
Transcription factor	1	1.6×	0.608
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NDP	Other/Unknown	no		Norrie_dis, Cys_knot_C, Glyco_hormone_CN
ATOH7	Transcription factor	no		bHLH_dom, ATOH7_bHLH, HLH_DNA-bd_sf
FZD4	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
TNPO1	Other/Unknown	no		Importin-beta_N, ARM-like, ARM-type_fold
MIP	Other/Unknown	no		MIP, MIP_CS, Aquaporin-like

Expression context

Cohort genes with no expression data: 0.

3 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
caudate nucleus	1
cranial nerve II	1
decidua	1
Brodmann (1909) area 9	1
prefrontal cortex	1
adipose tissue	1
right lung	1
subcutaneous adipose tissue	1
caput epididymis	1
cauda epididymis	1
corpus epididymis	1
primordial germ cell in gonad	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDP	197	broad	yes	cranial nerve II, decidua, caudate nucleus
ATOH7	104	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, prefrontal cortex, Brodmann (1909) area 9
FZD4	243	ubiquitous	marker	adipose tissue, subcutaneous adipose tissue, right lung
TNPO1	295	ubiquitous	marker	corpus epididymis, caput epididymis, cauda epididymis
MIP	91	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNPO1	3,147
MIP	2,496
FZD4	1,869
NDP	1,461
ATOH7	1,076

Intra-cohort edges

A	B	Sources
FZD4	NDP	biogrid_interaction, intact, string_interaction

Structural data

PDB: 3 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNPO1	Q92973	21
NDP	Q00604	12
FZD4	Q9ULV1	11

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MIP	P30301	91.08
ATOH7	Q8N100	72.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 5 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
Signaling by RNF43 mutants	1	423.0×	0.016	FZD4
Passive transport by Aquaporins	1	292.8×	0.016	MIP
WNT5A-dependent internalization of FZD4	1	253.8×	0.016	FZD4
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	1	211.5×	0.016	TNPO1
Regulation of FZD by ubiquitination	1	173.0×	0.016	FZD4
Postmitotic nuclear pore complex (NPC) reformation	1	135.9×	0.016	TNPO1
Aquaporin-mediated transport	1	122.8×	0.016	MIP
Asymmetric localization of PCP proteins	1	68.0×	0.021	FZD4
Intraflagellar transport	1	66.8×	0.021	TNPO1
Class B/2 (Secretin family receptors)	1	63.4×	0.021	FZD4
Ca2+ pathway	1	59.5×	0.021	FZD4
Cargo recognition for clathrin-mediated endocytosis	1	34.9×	0.033	FZD4
Clathrin-mediated endocytosis	1	28.4×	0.037	FZD4
Transport of small molecules	1	8.4×	0.115	MIP

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
extracellular matrix-cell signaling	2	1348.2×	3e-05	NDP, FZD4
Norrin signaling pathway	2	1348.2×	3e-05	NDP, FZD4
retinal blood vessel morphogenesis	2	963.0×	4e-05	NDP, FZD4
establishment of blood-brain barrier	2	561.7×	9e-05	NDP, FZD4
optic nerve development	2	481.5×	1e-04	NDP, ATOH7
endothelial cell differentiation	2	449.4×	1e-04	NDP, FZD4
lens development in camera-type eye	2	149.8×	8e-04	NDP, MIP
cerebellum vasculature morphogenesis	1	3370.4×	0.003	FZD4
positive regulation of retinal ganglion cell axon guidance	1	3370.4×	0.003	ATOH7
canonical Wnt signaling pathway	2	61.3×	0.003	NDP, FZD4
progesterone secretion	1	1685.2×	0.004	FZD4
retina blood vessel maintenance	1	1685.2×	0.004	NDP
re-entry into mitotic cell cycle	1	1123.5×	0.005	NDP
Wnt signaling pathway, calcium modulating pathway	1	842.6×	0.006	FZD4
cone retinal bipolar cell differentiation	1	842.6×	0.006	NDP
retina vasculature morphogenesis in camera-type eye	1	674.1×	0.007	FZD4
glycine metabolic process	1	561.7×	0.007	NDP
regulation of vascular endothelial growth factor receptor signaling pathway	1	561.7×	0.007	FZD4
gap junction-mediated intercellular transport	1	561.7×	0.007	MIP
establishment of blood-retinal barrier	1	561.7×	0.007	NDP
visual perception	2	31.8×	0.007	NDP, MIP
locomotion involved in locomotory behavior	1	481.5×	0.007	FZD4
maintenance of lens transparency	1	421.3×	0.007	MIP
positive regulation of neuron projection arborization	1	421.3×	0.007	FZD4
retinal rod cell differentiation	1	374.5×	0.007	NDP
microglial cell proliferation	1	374.5×	0.007	NDP
ubiquitin-dependent endocytosis	1	374.5×	0.007	NDP
retinal pigment epithelium development	1	337.0×	0.007	NDP
L-serine metabolic process	1	337.0×	0.007	NDP
homotypic cell-cell adhesion	1	337.0×	0.007	MIP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 2 of 5 evidence-associated genes (40%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NDP	0	0
ATOH7	0	0
FZD4	0	0
TNPO1	0	0
MIP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
FZD4	7	Functional:6, Binding:1
TNPO1	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	FZD4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	NDP, ATOH7, TNPO1, MIP

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)
NDP	0	—
ATOH7	0	—
FZD4	7	—
TNPO1	7	—
MIP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.