Oocyte/zygote/embryo maturation arrest 21

Summary

Oocyte/zygote/embryo maturation arrest 21 (MONDO:0957961) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oocyte/zygote/embryo maturation arrest 21
Mondo ID	MONDO:0957961
OMIM	620610
UMLS	C5882722
MedGen	1845812
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants.

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 21

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 19, oocyte/zygote/embryo maturation arrest 20, 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

5 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2663865	NM_001114122.3(CHEK1):c.1136G>A (p.Arg379Gln)	CHEK1	Pathogenic	no assertion criteria provided
2663866	NM_001114122.3(CHEK1):c.1324del (p.Arg442fs)	CHEK1	Pathogenic	no assertion criteria provided
2663867	NM_001114122.3(CHEK1):c.1325G>A (p.Arg442Gln)	CHEK1	Pathogenic	no assertion criteria provided
2663868	NM_001114122.3(CHEK1):c.1259G>A (p.Arg420Lys)	CHEK1	Pathogenic	no assertion criteria provided
3064152	NM_001114122.3(CHEK1):c.563C>G (p.Pro188Arg)	CHEK1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
CHEK1	HGNC:1925	ENSG00000149554	O14757	Serine/threonine-protein kinase Chk1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHEK1	Serine/threonine-protein kinase Chk1	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CHEK1	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_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
oocyte	1
primordial germ cell in gonad	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHEK1	210	ubiquitous	marker	secondary oocyte, oocyte, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHEK1	4,939

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHEK1	O14757	164

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	1	671.8×	0.008	CHEK1
Activation of ATR in response to replication stress	1	300.5×	0.008	CHEK1
Transcriptional Regulation by E2F6	1	292.8×	0.008	CHEK1
Presynaptic phase of homologous DNA pairing and strand exchange	1	271.9×	0.008	CHEK1
Signaling by SCF-KIT	1	248.3×	0.008	CHEK1
Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A	1	203.9×	0.008	CHEK1
TP53 Regulates Transcription of DNA Repair Genes	1	181.3×	0.008	CHEK1
G2/M DNA damage checkpoint	1	120.2×	0.009	CHEK1
Regulation of TP53 Activity through Phosphorylation	1	117.7×	0.009	CHEK1
Processing of DNA double-strand break ends	1	114.2×	0.009	CHEK1

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
regulation of mitotic centrosome separation	1	3370.4×	0.003	CHEK1
negative regulation of mitotic nuclear division	1	2407.4×	0.003	CHEK1
negative regulation of G0 to G1 transition	1	2407.4×	0.003	CHEK1
apoptotic process involved in development	1	1685.2×	0.003	CHEK1
inner cell mass cell proliferation	1	991.3×	0.003	CHEK1
regulation of double-strand break repair via homologous recombination	1	991.3×	0.003	CHEK1
replicative senescence	1	991.3×	0.003	CHEK1
peptidyl-threonine phosphorylation	1	887.0×	0.003	CHEK1
signal transduction in response to DNA damage	1	802.5×	0.003	CHEK1
mitotic G2/M transition checkpoint	1	802.5×	0.003	CHEK1
nucleus organization	1	561.7×	0.004	CHEK1
mitotic G2 DNA damage checkpoint signaling	1	443.5×	0.004	CHEK1
positive regulation of cell cycle	1	443.5×	0.004	CHEK1
negative regulation of gene expression, epigenetic	1	401.2×	0.004	CHEK1
DNA damage checkpoint signaling	1	391.9×	0.004	CHEK1
regulation of signal transduction by p53 class mediator	1	383.0×	0.004	CHEK1
G2/M transition of mitotic cell cycle	1	312.1×	0.005	CHEK1
cellular response to mechanical stimulus	1	216.1×	0.006	CHEK1
DNA replication	1	165.2×	0.008	CHEK1
regulation of cell population proliferation	1	115.4×	0.011	CHEK1
chromatin remodeling	1	73.0×	0.016	CHEK1
protein phosphorylation	1	68.0×	0.017	CHEK1
DNA repair	1	63.8×	0.017	CHEK1
DNA damage response	1	53.5×	0.019	CHEK1
apoptotic process	1	28.7×	0.035	CHEK1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
CHEK1	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHEK1	36	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	CHEK1
NERATINIB	4	CHEK1
PALBOCICLIB	4	CHEK1
BOSUTINIB	4	CHEK1
BRIGATINIB	4	CHEK1
NINTEDANIB	4	CHEK1
SUNITINIB	4	CHEK1
MIDOSTAURIN	4	CHEK1
DACTOLISIB	3	CHEK1
DOVITINIB	3	CHEK1
LESTAURTINIB	3	CHEK1
RUBOXISTAURIN	3	CHEK1
SILMITASERTIB	2	CHEK1
REFAMETINIB	2	CHEK1
SU-014813	2	CHEK1
CENISERTIB	2	CHEK1
SCH-900776	2	CHEK1
RABUSERTIB	2	CHEK1
PREXASERTIB	2	CHEK1
BMS-690514	2	CHEK1
MIVAVOTINIB	2	CHEK1
CERDULATINIB	2	CHEK1
R-406	2	CHEK1
AT-9283	2	CHEK1
TOZASERTIB	2	CHEK1
UCN-01	2	CHEK1
PELITINIB	2	CHEK1
KW-2449	1	CHEK1
RG-1530	1	CHEK1
AZD-7762	1	CHEK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CHEK1	1,086	Binding:1039, Functional:44, ADMET:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CHEK1	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CHEK1	1,086

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

30 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)
FEDRATINIB	4	CHEK1
NERATINIB	4	CHEK1
PALBOCICLIB	4	CHEK1
BOSUTINIB	4	CHEK1
BRIGATINIB	4	CHEK1
NINTEDANIB	4	CHEK1
SUNITINIB	4	CHEK1
MIDOSTAURIN	4	CHEK1
DACTOLISIB	3	CHEK1
DOVITINIB	3	CHEK1
LESTAURTINIB	3	CHEK1
RUBOXISTAURIN	3	CHEK1
SILMITASERTIB	2	CHEK1
REFAMETINIB	2	CHEK1
SU-014813	2	CHEK1
CENISERTIB	2	CHEK1
SCH-900776	2	CHEK1
RABUSERTIB	2	CHEK1
PREXASERTIB	2	CHEK1
BMS-690514	2	CHEK1
MIVAVOTINIB	2	CHEK1
CERDULATINIB	2	CHEK1
R-406	2	CHEK1
AT-9283	2	CHEK1
TOZASERTIB	2	CHEK1
UCN-01	2	CHEK1
PELITINIB	2	CHEK1
KW-2449	1	CHEK1
RG-1530	1	CHEK1
AZD-7762	1	CHEK1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CHEK1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.