WEE2

protein-coding

WEE2 oocyte meiosis inhibiting kinase

Gene summary

Predicted to enable protein tyrosine kinase activity. Predicted to be involved in several processes, including female pronucleus assembly; negative regulation of cyclin-dependent protein serine/threonine kinase activity; and regulation of meiotic cell cycle. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001105558.1

Inheritance

ClinVar variants

P:8U:80B:16

Top phenotype

Oocyte/zygote/embryo maturation arrest 5

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr7:141,708,353-141,731,271

External References & Databases

Ensembl (ENSG00000214102)

Transcript & Mutation Effects

hg38 • Region Span ~22.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

oocyte maturation defect 5DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0020837

Submitter: Ambry Genetics

oocyte maturation defect 5LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020837

Submitter: Ambry Genetics

oocyte maturation defect 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020837

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Oocyte/zygote/embryo maturation arrest 5AR

Manifestation: Obstetric

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 29606300; 30628060

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WEE2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 77

not providedTotal: 15

Oocyte maturation defect 5Total: 8

WEE2-related disorderTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001105558.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		2 clinvar	6 clinvar	1 clinvar	10
missense	2 clinvar		76 clinvar	9 clinvar		87
nonsense	2 clinvar					2
start loss						0
frameshift	2 clinvar	1 clinvar				3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	7	1	80	15	1	104

Highest pathogenic variant AF is 0.000058240035

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001105558.1	RefSeq	NP_001099028.1	12	MANE Select
ENST00000397541.6	Ensembl	ENSP00000380675.2	12	MANE Select
ENST00000493845.1	Ensembl	ENSP00000420388.1	6	Standard
ENST00000956320.1	Ensembl	ENSP00000626379.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell cycle - Homo sapiens (human)

Biological Process

mitotic cell cycle checkpoint
female meiotic nuclear division
peptidyl-tyrosine phosphorylation
female pronucleus assembly
positive regulation of phosphorylation

Molecular Function

magnesium ion binding
protein kinase activity
protein tyrosine kinase activity
non-membrane spanning protein tyrosine kinase activity
ATP binding

Cellular Component

nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397541
Coding exons: 12
Length: 22919
Individuals with no LoFs: 124734
Homozygous LoFs: 0
Heterozygous LoFs: 59
Defined: 124793
p: 0.000236

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.579	280	309	0.907	0.0000159	3716
Missense (PolyPhen)		73	96.032	0.76017		1225
Synonymous	-0.228	114	111	1.03	0.00000569	1091
Loss of Function	2.38	13	26.2	0.497	0.00000120	351

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00019	rare
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0.0022	0.0022	notable
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0.00023	0.00023	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Oocyte-specific protein tyrosine kinase that phosphorylates and inhibits CDK1 and acts as a key regulator of meiosis during both prophase I and metaphase II. Required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, by phosphorylating CDK1 at 'Tyr-15', leading to inhibit CDK1 activity and prevent meiotic reentry. Also required for metaphase II exit during egg activation by phosphorylating CDK1 at 'Tyr-15', to ensure exit from meiosis in oocytes and promote pronuclear formation (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.765
RVIS EVS: -0.6
RVIS percentile EVS: 18.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.168

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium