Oocyte maturation defect 3

Summary

Oocyte maturation defect 3 (MONDO:0021574) is a disease caused by ZP3 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: ZP3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oocyte maturation defect 3
Mondo ID	MONDO:0021574
OMIM	617712
UMLS	C4540205
MedGen	1617317
Is cancer (heuristic)	no

Also known as: oocyte maturation defect 3 · OOMD3

Data availability: 8 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 › inherited oocyte maturation defect › oocyte maturation defect 3

Related subtypes (23): female infertility due to zona pellucida defect, oocyte maturation defect 5, oocyte maturation defect 2, oocyte maturation defect 4, oocyte maturation defect 11, oocyte maturation defect 12, oocyte maturation defect 10, oocyte maturation defect 6, oocyte maturation defect 7, oocyte maturation defect 8, oocyte maturation defect 9, oocyte maturation defect 13, oocyte maturation defect 14, oocyte/zygote/embryo maturation arrest 17, oocyte/zygote/embryo maturation arrest 18, oocyte/zygote/embryo maturation arrest 19, oocyte/zygote/embryo maturation arrest 20, oocyte/zygote/embryo maturation arrest 21, oocyte/zygote/embryo maturation arrest 22, oocyte/zygote/embryo maturation arrest 23, oocyte/zygote/embryo maturation arrest 24, oocyte/zygote/embryo maturation arrest 25, oocyte/zygote/embryo maturation arrest 16

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

8 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 pathogenic, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
695115	NM_207341.4(ZP1):c.769C>T (p.Gln257Ter)	ZP1	Pathogenic	criteria provided, single submitter
437933	NM_001110354.2(ZP3):c.400G>A (p.Ala134Thr)	ZP3	Pathogenic	no assertion criteria provided
689403	NM_001110354.2(ZP3):c.763C>G (p.Arg255Gly)	ZP3	Pathogenic	no assertion criteria provided
1333775	NM_001110354.2(ZP3):c.157dup (p.Val53fs)	ZP3	Likely pathogenic	criteria provided, single submitter
2518482	NM_001110354.2(ZP3):c.623T>C (p.Val208Ala)	ZP3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3068101	NM_001110354.2(ZP3):c.581A>T (p.Asp194Val)	ZP3	Uncertain significance	criteria provided, single submitter
4081039	NM_001110354.2(ZP3):c.432-8TC[2]	ZP3	Uncertain significance	criteria provided, single submitter
768162	NM_001110354.2(ZP3):c.923+8_923+10del	ZP3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
ZP3	Strong	Autosomal dominant	oocyte maturation defect 3	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ZP3	Orphanet:404466	Female infertility due to zona pellucida defect
ZP1	Orphanet:404466	Female infertility due to zona pellucida defect

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
ZP3	HGNC:13189	ENSG00000188372	P21754	Zona pellucida sperm-binding protein 3	gencc,clinvar
ZP1	HGNC:13187	ENSG00000149506	P60852	Zona pellucida sperm-binding protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZP3	Zona pellucida sperm-binding protein 3	Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy.
ZP1	Zona pellucida sperm-binding protein 1	Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy.

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZP3	Other/Unknown	no		ZP_dom, ZP_dom_CS, ZP-C_dom
ZP1	Antibody/Immunoglobulin	yes		P_trefoil_dom, ZP_dom, P_trefoil_CS

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
lower esophagus mucosa	1
primordial germ cell in gonad	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZP3	134	ubiquitous	marker	lower esophagus mucosa, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
ZP1	143	tissue_specific	yes	oocyte, male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZP1	1,139
ZP3	805

Intra-cohort edges

A	B	Sources
ZP1	ZP3	intact, string_interaction

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZP3	P21754	77.32
ZP1	P60852	73.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interaction With Cumulus Cells And The Zona Pellucida	2	1038.2×	8e-07	ZP3, ZP1

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
binding of sperm to zona pellucida	2	421.3×	1e-04	ZP3, ZP1
positive regulation of type IV hypersensitivity	1	8426.0×	6e-04	ZP3
egg coat formation	1	8426.0×	6e-04	ZP3
positive regulation of antral ovarian follicle growth	1	8426.0×	6e-04	ZP3
positive regulation of acrosomal vesicle exocytosis	1	4213.0×	8e-04	ZP3
positive regulation of ovarian follicle development	1	4213.0×	8e-04	ZP3
positive regulation of humoral immune response	1	2106.5×	0.001	ZP3
negative regulation of binding of sperm to zona pellucida	1	2106.5×	0.001	ZP3
humoral immune response mediated by circulating immunoglobulin	1	1685.2×	0.001	ZP3
prevention of polyspermy	1	1404.3×	0.001	ZP1
positive regulation of acrosome reaction	1	766.0×	0.002	ZP3
positive regulation of leukocyte migration	1	495.6×	0.003	ZP3
oocyte development	1	468.1×	0.003	ZP3
blastocyst formation	1	383.0×	0.004	ZP3
positive regulation of interleukin-4 production	1	280.9×	0.005	ZP3
positive regulation of T cell proliferation	1	129.6×	0.010	ZP3
positive regulation of type II interferon production	1	112.3×	0.010	ZP3
positive regulation of inflammatory response	1	72.6×	0.015	ZP3
negative regulation of DNA-templated transcription	1	15.8×	0.066	ZP3
positive regulation of DNA-templated transcription	1	14.0×	0.070	ZP3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ZP3	0	0
ZP1	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
ZP1	1	Binding:1

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	ZP1
E	Difficult family or no structure, no drug	1	ZP3

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)
ZP3	0	—
ZP1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.