Oocyte/zygote/embryo maturation arrest 19

Summary

Oocyte/zygote/embryo maturation arrest 19 (MONDO:0957231) is a disease caused by NLRP5 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NLRP5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oocyte/zygote/embryo maturation arrest 19
Mondo ID	MONDO:0957231
OMIM	620333
UMLS	C5830442
MedGen	1841078
Is cancer (heuristic)	no

Data availability: 10 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 › inherited oocyte maturation defect › oocyte/zygote/embryo maturation arrest 19

Related subtypes (23): female infertility due to zona pellucida defect, oocyte maturation defect 5, oocyte maturation defect 2, oocyte maturation defect 3, 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 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

10 retrieved; paginated sample, class counts are floors:

5 pathogenic, 2 pathogenic/likely pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
2499461	NC_000019.10:g.56027099G>A	LOC126862935	Pathogenic	no assertion criteria provided
2499463	NC_000019.10:g.56027515TTAG[1]	LOC126862935	Pathogenic	no assertion criteria provided
1697241	NC_000019.10:g.56027806AG[1]	NLRP5	Pathogenic/Likely pathogenic	no assertion criteria provided
1697243	NC_000019.10:g.56028063_56028064del	NLRP5	Pathogenic/Likely pathogenic	no assertion criteria provided
2499459	NC_000019.10:g.56003945C>T	NLRP5	Pathogenic	no assertion criteria provided
2499460	NC_000019.10:g.56028314C>T	NLRP5	Pathogenic	no assertion criteria provided
2499462	NC_000019.10:g.56058260C>T	NLRP5	Pathogenic	no assertion criteria provided
4849364	NM_001433705.1(NLRP5):c.725C>A (p.Ser242Ter)	LOC126862935	Likely pathogenic	criteria provided, single submitter
3780032	NM_001433705.1(NLRP5):c.-30del	NLRP5	Likely pathogenic	criteria provided, single submitter
3067909	NM_001433705.1(NLRP5):c.845_846del (p.Thr282fs)	LOC126862935	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
NLRP5	Strong	Autosomal recessive	oocyte/zygote/embryo maturation arrest 19	3

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
NLRP5	HGNC:21269	ENSG00000171487	P59047	NACHT, LRR and PYD domains-containing protein 5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NLRP5	NACHT, LRR and PYD domains-containing protein 5	Component of the subcortical maternal complex (SCMC), a multiprotein complex that plays a key role in early embryonic development.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NLRP5	Other/Unknown	no		Leu-rich_rpt, DAPIN, NACHT_NTPase

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
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NLRP5	22		marker	secondary oocyte, oocyte, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NLRP5	1,057

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NLRP5	P59047	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
cortical granule exocytosis	1	8426.0×	9e-04	NLRP5
establishment of organelle localization	1	5617.3×	9e-04	NLRP5
protein storage	1	3370.4×	9e-04	NLRP5
establishment of spindle localization	1	2808.7×	9e-04	NLRP5
positive regulation of embryonic development	1	1123.5×	0.002	NLRP5
regulation of cell division	1	766.0×	0.002	NLRP5
regulation of protein localization	1	205.5×	0.007	NLRP5
regulation of inflammatory response	1	168.5×	0.007	NLRP5
exocytosis	1	151.8×	0.007	NLRP5
actin filament organization	1	118.7×	0.008	NLRP5

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
NLRP5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
E	Difficult family or no structure, no drug	1	NLRP5

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)
NLRP5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.