WEE2

Summary

WEE2 (WEE2 oocyte meiosis inhibiting kinase, HGNC:19684) is a protein-coding gene on chromosome 7q34, encoding Wee1-like protein kinase 2 (P0C1S8). Oocyte-specific protein tyrosine kinase that phosphorylates and inhibits CDK1/CDC2 and acts as a key regulator of meiosis during both prophase I and metaphase II.

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.

Source: NCBI Gene 494551 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): oocyte maturation defect 5 (Definitive, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 115 total — 7 pathogenic
• GTEx eGene: eQTL in 16 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 9
• ChEMBL bioactivity: 13 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.03 (unconstrained)
• MANE Select transcript: NM_001105558

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19684
Approved symbol	WEE2
Name	WEE2 oocyte meiosis inhibiting kinase
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16107, WEE1B
Ensembl gene	ENSG00000214102
Ensembl biotype	protein_coding
OMIM	614084
Entrez	494551

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

MANE Select: ENST00000397541

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 1

ENST00000397541, ENST00000493845, ENST00000956320

RefSeq mRNA: 1 — MANE Select: NM_001105558 NM_001105558

CCDS: CCDS43660

Canonical transcript exons

ENST00000397541 — 12 exons

Exon	Start	End
ENSE00002430193	141725026	141725196
ENSE00002435326	141720935	141721056
ENSE00002447201	141714209	141714405
ENSE00002452229	141723941	141724048
ENSE00002462398	141724190	141724275
ENSE00002466375	141719072	141719244
ENSE00002467011	141727304	141727446
ENSE00002475135	141723134	141723280
ENSE00002482943	141708353	141709100
ENSE00002511151	141716222	141716267
ENSE00002519265	141729531	141729673
ENSE00002519956	141730295	141731271

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 91.16.

Highest expression (Bgee): primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, ganglionic eminence, endometrium, uterine tube.

Genetic regulation across tissues (GTEx eQTL / sQTL)

WEE2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	2.7e-14	-0.41	7:141738137:T:TTTCCAAACTTGAAACC
Adipose Subcutaneous	eqtl	3.9e-14	+0.38	7:141742852:A:G
Skin Not Sun Exposed Suprapubic	eqtl	9.3e-11	-0.37	7:141738137:T:TTTCCAAACTTGAAACC
Pancreas	eqtl	1.5e-08	+0.48	7:141755793:G:A
Minor Salivary Gland	eqtl	4.5e-05	-0.57	7:141712007:G:A
Esophagus Gastroesophageal Junction	eqtl	6.0e-05	+0.36	7:141822204:C:T
Nerve Tibial	eqtl	3.8e-04	+0.24	7:141755895:C:T
Thyroid	eqtl	4.8e-04	+0.24	7:141787249:T:C
Prostate	eqtl	1.6e-03	-0.42	7:141891545:A:G
Breast Mammary Tissue	eqtl	2.8e-03	+0.24	7:141755636:A:C
Small Intestine Terminal Ileum	eqtl	3.4e-03	-0.42	7:141907414:G:A
Artery Tibial	eqtl	7.1e-03	+0.21	7:141827647:T:TGCACA
Spleen	eqtl	1.5e-02	+0.36	7:141769619:C:G
Artery Aorta	eqtl	1.9e-02	+0.30	7:141812058:T:C
Pituitary	eqtl	4.1e-02	-1.14	7:141299696:C:T
Brain Caudate basal ganglia	eqtl	4.7e-02	-1.26	7:141674000:G:T

Top tissues by expression

showing 100 of 122 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.15	gold quality
ganglionic eminence	UBERON:0004023	52.55	gold quality
endometrium	UBERON:0001295	51.25	gold quality
right uterine tube	UBERON:0001302	50.59	gold quality
calcaneal tendon	UBERON:0003701	48.90	gold quality
islet of Langerhans	UBERON:0000006	48.78	gold quality
mucosa of stomach	UBERON:0001199	48.75	gold quality
lower esophagus mucosa	UBERON:0035834	47.88	gold quality
endocervix	UBERON:0000458	47.45	gold quality
pancreas	UBERON:0001264	46.39	gold quality
bone marrow cell	CL:0002092	46.22	gold quality
muscle tissue	UBERON:0002385	45.88	silver quality
ventricular zone	UBERON:0003053	45.81	gold quality
body of pancreas	UBERON:0001150	45.40	gold quality
descending thoracic aorta	UBERON:0002345	44.94	gold quality
smooth muscle tissue	UBERON:0001135	44.91	gold quality
bone marrow	UBERON:0002371	44.91	gold quality
right ovary	UBERON:0002118	44.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	44.06	gold quality
cortex of kidney	UBERON:0001225	43.88	silver quality
sural nerve	UBERON:0015488	43.62	gold quality
fallopian tube	UBERON:0003889	43.53	gold quality
cortical plate	UBERON:0005343	43.34	gold quality
muscle of leg	UBERON:0001383	43.18	gold quality
prefrontal cortex	UBERON:0000451	43.11	gold quality
ovary	UBERON:0000992	42.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	42.87	gold quality
adult mammalian kidney	UBERON:0000082	42.79	gold quality
kidney	UBERON:0002113	42.37	gold quality
left ovary	UBERON:0002119	42.36	silver quality
uterine cervix	UBERON:0000002	42.27	gold quality
gastrocnemius	UBERON:0001388	41.98	gold quality
corpus callosum	UBERON:0002336	41.75	silver quality
popliteal artery	UBERON:0002250	41.47	gold quality
metanephros cortex	UBERON:0010533	41.43	silver quality
body of uterus	UBERON:0009853	41.38	silver quality
tibial artery	UBERON:0007610	41.33	gold quality
right lung	UBERON:0002167	41.31	gold quality
superior frontal gyrus	UBERON:0002661	40.97	gold quality
lymph node	UBERON:0000029	40.91	gold quality
granulocyte	CL:0000094	40.60	gold quality
skin of leg	UBERON:0001511	40.59	silver quality
zone of skin	UBERON:0000014	40.50	silver quality
thoracic aorta	UBERON:0001515	40.37	silver quality
tibial nerve	UBERON:0001323	40.13	silver quality
frontal cortex	UBERON:0001870	40.09	gold quality
skin of abdomen	UBERON:0001416	40.08	gold quality
mucosa of transverse colon	UBERON:0004991	39.98	silver quality
ascending aorta	UBERON:0001496	39.91	silver quality
myometrium	UBERON:0001296	39.80	gold quality
fundus of stomach	UBERON:0001160	39.71	gold quality
thoracic mammary gland	UBERON:0005200	39.68	gold quality
right adrenal gland cortex	UBERON:0035827	39.68	silver quality
left adrenal gland cortex	UBERON:0035825	39.63	gold quality
saliva-secreting gland	UBERON:0001044	39.37	gold quality
rectum	UBERON:0001052	39.28	silver quality
urinary bladder	UBERON:0001255	39.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	39.24	silver quality
putamen	UBERON:0001874	39.05	silver quality
caudate nucleus	UBERON:0001873	39.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	39.01	silver quality
nucleus accumbens	UBERON:0001882	38.97	gold quality
right adrenal gland	UBERON:0001233	38.92	silver quality
left coronary artery	UBERON:0001626	38.85	silver quality
stomach	UBERON:0000945	38.82	silver quality
minor salivary gland	UBERON:0001830	38.80	silver quality
right lobe of thyroid gland	UBERON:0001119	38.78	silver quality
stromal cell of endometrium	CL:0002255	38.77	gold quality
pituitary gland	UBERON:0000007	38.75	silver quality
amygdala	UBERON:0001876	38.69	gold quality
apex of heart	UBERON:0002098	38.69	silver quality
temporal lobe	UBERON:0001871	38.57	gold quality
thyroid gland	UBERON:0002046	38.52	gold quality
spleen	UBERON:0002106	38.51	silver quality
subcutaneous adipose tissue	UBERON:0002190	38.50	gold quality
multicellular organism	UBERON:0000468	38.43	gold quality
brain	UBERON:0000955	38.35	gold quality
body of stomach	UBERON:0001161	38.33	silver quality
cerebral cortex	UBERON:0000956	38.25	gold quality
leukocyte	CL:0000738	37.80	gold quality
right coronary artery	UBERON:0001625	37.74	silver quality
left adrenal gland	UBERON:0001234	37.71	gold quality
ectocervix	UBERON:0012249	37.60	silver quality
substantia nigra	UBERON:0002038	37.57	silver quality
left lobe of thyroid gland	UBERON:0001120	37.50	gold quality
heart	UBERON:0000948	37.46	gold quality
adrenal gland	UBERON:0002369	37.34	gold quality
anterior cingulate cortex	UBERON:0009835	37.33	silver quality
adipose tissue	UBERON:0001013	37.31	gold quality
heart left ventricle	UBERON:0002084	37.23	silver quality
adrenal tissue	UBERON:0018303	37.23	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
prostate gland	UBERON:0002367	37.16	gold quality
muscle layer of sigmoid colon	UBERON:0035805	37.14	silver quality
vagina	UBERON:0000996	37.03	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	37.01	silver quality
lower esophagus	UBERON:0013473	36.96	silver quality
placenta	UBERON:0001987	36.92	gold quality
lung	UBERON:0002048	36.91	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.46

HPA expression

RNA tissue specificity: Not detected

56 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Corpus callosum	tissue	2.4
Substantia nigra	tissue	1.3
Spinal cord	tissue	1.3
Periaqueductal gray	tissue	1.3
Olfactory bulb	tissue	1.3
Putamen	tissue	1.2
Medulla oblongata	tissue	1.2
Septum	tissue	1.2
Amygdala	tissue	1.1
Thalamus	tissue	1.1
Ventral forebrain	tissue	1.1
Midbrain	tissue	1.0
Cerebellum	tissue	1.0
Hippocampal formation	tissue	1.0
Pons	tissue	0.9
Basal ganglia	tissue	0.9
Hypothalamus	tissue	0.9
Cerebral cortex	tissue	0.8
Superior colliculi	tissue	0.8
Retrosplenial and cingulate cortex	tissue	0.8
Retrosplenial cortex	tissue	0.8
Motor cortex	tissue	0.7
Insular cortex	tissue	0.7
Skin 1	tissue	0.6
Prefrontal cortex	tissue	0.6
Entorhinal cortex	tissue	0.6
Temporal cortex	tissue	0.6
Occipital cortex	tissue	0.6
Somatosensory cortex	tissue	0.5
Lymph node	tissue	0.4
Nucleus accumbens	tissue	0.4
Choroid plexus	tissue	0.4
Thyroid gland	tissue	0.4
Testis	tissue	0.3
Heart muscle	tissue	0.3
Esophagus	tissue	0.3
Gallbladder	tissue	0.3
Kidney	tissue	0.3
Locus coeruleus	tissue	0.3
Hippocampus	tissue	0.3
Postcentral gyrus	tissue	0.3
Stomach 1	tissue	0.2
Retina	tissue	0.2
Adipose tissue	tissue	0.2
Salivary gland	tissue	0.2
Skeletal muscle	tissue	0.2
Pancreas	tissue	0.2
Pituitary gland	tissue	0.1
Ovary	tissue	0.1
Endometrium 1	tissue	0.1
Lung	tissue	0.1
Spleen	tissue	0.1
Small intestine	tissue	0.1
Prostate	tissue	0.1
Fallopian tube	tissue	0.1
Appendix	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — White matter (2.4), Ventral spinal cord (1.3), Dorsal spinal cord (1.2), Dorsal hippocampus (1.0), Ventral hippocampus (0.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting WEE2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 61 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3177-5P	99.65	70.38	1174

Functional genomics

gnomAD constraint: pLI 7.97e-14, LOEUF 1.03, missense Z 1.25 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000397541 — one region, missense o/e 0.92.

Literature-anchored findings (GeneRIF, showing 9)

• homozygous mutations in WEE2 that are responsible for fertilization failure in humans, were identified. (PMID:29606300)
• WEE2-AS1 over-expressed in HCC and was positively correlated to hepatitis B virus (HBV) infection, hepatic vascular invasion, poor tumor differentiation and poor patient prognosis. WEE2-AS1 also accelerated the proliferation, migration, invasion and cell cycle progression of HCC cells. A preliminary HBx-WEE2-AS1- FERMT3 pathway which may serve as a therapeutic target for HBV-associated HCC. (PMID:30471857)
• These findings confirmed our previous research and expanded the mutational spectrum of WEE2, making it a potential genetic diagnostic marker for those suffering from human fertilization failure. (PMID:30628060)
• A high prevalence of WEE2 mutations was found in Chinese women experiencing fertilization failure or poor fertilization. (PMID:30827523)
• Novel variants found in WEE2, which is autosomal-recessive inherited, may be related to recurrent pronucleus formation failure and female infertility. (PMID:30827524)
• Novel compound heterozygous mutations c.598C>T (p.Arg200Ter) and c.1319G>C (p.Trp440Ser) in WEE2 gene in a female whose oocytes could not form pronucleus after intracytoplasmic sperm injection. Mutations in WEE2 gene affect the normal function of WEE2 proteins and cause fertilization failure. (PMID:31428887)
• Clinical exome sequencing identifies novel compound heterozygous mutations of the WEE2 gene in primary infertile women with fertilization failure. (PMID:33904356)
• Novel WEE2 compound heterozygous mutations identified in patients with fertilization failure or poor fertilization. (PMID:34476630)
• Novel WEE2 homozygous mutations c.1346C>T and c.949A>T identified in primary infertile women due to unexplained fertilization failure. (PMID:37772619)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	wee2	ENSDARG00000012718
mus_musculus	Wee2	ENSMUSG00000037159
rattus_norvegicus	Wee2	ENSRNOG00000026446
drosophila_melanogaster	Wee1	FBGN0011737

Paralogs (8): EIF2AK2 (ENSG00000055332), EIF2AK1 (ENSG00000086232), STK35 (ENSG00000125834), PKMYT1 (ENSG00000127564), EIF2AK4 (ENSG00000128829), WEE1 (ENSG00000166483), EIF2AK3 (ENSG00000172071), PDIK1L (ENSG00000175087)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:3027899) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased bone mineral density	1
decreased locomotor activity	1
decreased exploration in new environment	1
reduced female fertility	1
decreased litter size	1
decreased circulating iron level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Atheris squamigera	Q8AX02	99.3%	Diamond
Xenopus laevis	O57473	98.7%	Diamond
Xenopus tropicalis	A4QNA8	89.7%	Diamond
Ailuropoda melanoleuca	D2HHP1	89.2%	Diamond
Canis lupus familiaris	E2RSS3	89.2%	Diamond
Sus scrofa	A4PES0	79.0%	Diamond
Caenorhabditis elegans	O18209	68.7%	Diamond
Caenorhabditis briggsae	Q626B1	68.4%	Diamond
Gallus gallus	E1BTE1	62.5%	Diamond
Arabidopsis thaliana	Q8L4H0	56.5%	Diamond
Schizosaccharomyces pombe 972h-	O13889	53.2%	Diamond
Oryza sativa Japonica Group	Q6Z829	52.7%	Diamond
Dictyostelium discoideum	Q54RP7	49.1%	Diamond
Saccharomyces cerevisiae S288C	P32944	43.3%	Diamond
Drechslerella dactyloides	A0AAD6IZ24	38.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
WEE2-AS1	ncRNA	285962
TAS2R3	protein-coding	50831
AGK	protein-coding	55750
DENND11	protein-coding	57189
SSBP1	protein-coding	6742
TMEM178B	protein-coding	100507421
AGK-DT	ncRNA	105375538
TAS2R4	protein-coding	50832

Protein

Protein identifiers

Wee1-like protein kinase 2 — P0C1S8 (reviewed: P0C1S8)

Alternative names: Wee1-like protein kinase 1B, Wee1B kinase

All UniProt accessions (2): P0C1S8, H7C5P0

UniProt curated annotations — full annotation on UniProt →

Function. Oocyte-specific protein tyrosine kinase that phosphorylates and inhibits CDK1/CDC2 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.

Subcellular location. Nucleus.

Tissue specificity. Expressed in oocytes (at protein level). May also be expressed in testis.

Post-translational modifications. Phosphorylated on serine residues. Phosphorylation leads to increase its activity.

Disease relevance. Oocyte/zygote/embryo maturation arrest 5 (OZEMA5) [MIM:617996] An autosomal recessive infertility disorder characterized by oocyte inability to exit metaphase II, resulting in fertilization failure. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily.

RefSeq proteins (1): NP_001099028* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017164	Wee1-like_protein_kinase	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR050339	CC_SR_Kinase	Family

Pfam: PF00069

Catalyzed reactions (Rhea)

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (51 total): helix 13, strand 10, sequence variant 6, compositionally biased region 4, binding site 4, turn 3, region of interest 2, sequence conflict 2, short sequence motif 2, chain 1, domain 1, active site 1, modified residue 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
5VDK	Crystal structure of human WEE2 kinase domain in complex with MK1775	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C1S8-F1	67.50	0.41

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH uncertain · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
339	proton acceptor

Ligand- & substrate-binding residues (4)

Position	Role
218–226	ATP
241	ATP
344	Mg(2+)
380	Mg(2+)

Post-translational modifications (1)

Type	Positions
Phosphoserine	76

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 108 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_CELL_MATURATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_OOGENESIS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_ORGANELLE_FISSION, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_CELL_MATURATION, GOBP_NUCLEUS_ORGANIZATION

GO Biological Process (9): mitotic cell cycle (GO:0000278), female meiotic nuclear division (GO:0007143), female pronucleus assembly (GO:0035038), positive regulation of phosphorylation (GO:0042327), regulation of meiosis I (GO:0060631), regulation of fertilization (GO:0080154), negative regulation of oocyte maturation (GO:1900194), protein phosphorylation (GO:0006468), meiotic cell cycle (GO:0051321)

GO Molecular Function (9): magnesium ion binding (GO:0000287), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

GO top-level categories

40 GO namespaces:

Category	Terms
cell cycle	2
meiotic nuclear division	2
phosphorylation	2
cellular anatomical structure	2
mitotic nuclear division	1
female gamete generation	1
meiotic cell cycle	1
nucleus organization	1
single fertilization	1
organelle assembly	1
regulation of phosphorylation	1
positive regulation of phosphate metabolic process	1
meiosis I	1
regulation of meiotic nuclear division	1
fertilization	1
regulation of reproductive process	1
oocyte maturation	1
regulation of oocyte maturation	1
negative regulation of cell maturation	1
negative regulation of reproductive process	1
protein modification process	1
sexual reproduction	1
reproductive process	1
metal ion binding	1
protein kinase activity	1
protein tyrosine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
nucleoplasm	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,016 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WEE2	PATL2	C9JE40	700
WEE2	TLE6	Q9H808	621
WEE2	BTG4	Q9NY30	576
WEE2	TUBB8	Q3ZCM7	570
WEE2	CDC25B	P30305	563
WEE2	PLCZ1	Q86YW0	556
WEE2	CDK1	P06493	546
WEE2	FBXO43	Q4G163	536
WEE2	ACTL9	Q8TC94	531
WEE2	ZP3	P21754	488
WEE2	ZP2	Q05996	476
WEE2	ZAR1	Q86SH2	472
WEE2	DNAH17	Q9UFH2	466
WEE2	NLRP5	P59047	466
WEE2	ACTL7A	Q9Y615	463

IntAct

BioGRID (2 interactions; top human partners by supporting records): MYC (Dosage Lethality)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
WEE2	“down-regulates activity”	CDK1	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for WEE2: 115 ClinVar records (7 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

115 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	0
Uncertain significance	73
Likely benign	15
Benign	2

Top pathogenic / likely-pathogenic (7)

Showing all 7 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2163249	NM_001105558.1(WEE2):c.862C>T (p.Gln288Ter)	Pathogenic	criteria provided, single submitter	1
4796631	NM_001105558.1(WEE2):c.1007_1008dup (p.His337fs)	Pathogenic	criteria provided, single submitter	1
545469	NM_001105558.1(WEE2):c.700G>C (p.Asp234His)	Pathogenic	no assertion criteria provided	1
545470	NM_001105558.1(WEE2):c.1477dup (p.Thr493fs)	Pathogenic	no assertion criteria provided	1
977295	NM_001105558.1(WEE2):c.1228C>T (p.Arg410Trp)	Pathogenic	no assertion criteria provided	1
977296	NM_001105558.1(WEE2):c.1221G>A (p.Glu407=)	Pathogenic	no assertion criteria provided	1
977297	NM_001105558.1(WEE2):c.598C>T (p.Arg200Ter)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore WEE2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 782):

Position(s)	Effect	Δscore	Sites
7:141716220	acceptor_gain	1.0000
7:141719245–141719246	donor_loss	1.0000	3
7:141720925	acceptor_gain	1.0000
7:141720933–141720934	acceptor_loss	1.0000	6
7:141721057–141721058	donor_loss	1.0000	4
7:141723940	acceptor_loss	1.0000	2
7:141727287–141727288	acceptor_gain	1.0000	2
7:141727295–141727297	acceptor_gain	1.0000	2
7:141727443	donor_gain	1.0000
7:141715323	donor_gain	0.9900

AlphaMissense

694 missense substitutions predicted likely pathogenic (of 3,727 scored), across 191 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D416	8	0.966	0.984
D339	8	0.965	0.990
F212	8	0.942	0.997
H337	8	0.930	0.982
F418	8	0.927	0.993
D234	8	0.925	0.970
H331	8	0.923	0.983
D380	8	0.907	0.968
D396	8	0.862	0.918
W279	7	0.992	0.997
F399	7	0.959	0.993
W440	7	0.945	0.980
K241	7	0.941	0.995
C292	7	0.935	0.986
E290	7	0.926	0.986
F158	7	0.910	0.978
E403	7	0.907	0.958
K341	7	0.906	0.982
N344	7	0.904	0.950
F346	7	0.904	0.954

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:614084 | disease phenotypes: MIM:617996

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
oocyte maturation defect 5	Definitive	Autosomal recessive	3

Mondo (1): oocyte maturation defect 5 (MONDO:0020837)

HPO phenotypes

9 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000147	Polycystic ovaries
HP:0008222	Female infertility
HP:0008669	Abnormal spermatogenesis
HP:0011462	Young adult onset
HP:0020155	Abnormal oocyte morphology
HP:0031515	Abnormal meiosis
HP:0031516	Metaphase I oocyte maturation arrest
HP:0034719	Lack of oocyte pronucleus formation

GWAS associations

3 associations:

Study	Trait	p-value
GCST001961_8	Anorexia nervosa	2e-7
GCST008017_2	Bitter taste perception (6-n-propylthiouracil) in obesity with metabolic syndrome	4e-7
GCST008019_3	Bitter taste perception (phenylthiocarbamide) in obesity with metabolic syndrome	5e-7

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5095 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 42,101 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

13 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL5416410	DASATINIB	4	674
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL180022	NERATINIB	4	9,891
CHEMBL603469	LESTAURTINIB	3
CHEMBL1976040	ADAVOSERTIB	2	1,844
CHEMBL564829	MILCICLIB	2	871
CHEMBL607707	PELITINIB	2	6,569
CHEMBL475251	R-406	2	787
CHEMBL572878	TOZASERTIB	2	3,128
CHEMBL1908397	KW-2449	1	655
CHEMBL49120	PD-0166285	1	477
CHEMBL4289017	PF-03814735	1	566

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — WEE family

Binding affinities (BindingDB)

22 measured of 80 human assays (81 total across all organisms); most potent 22 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
CEP-701	KD	3.4 nM
Staurosporine, 8	IC50	6.5 nM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	KI	15 nM	US-10981896: Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase
CHEMBL1240703	KD	15 nM
2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide	IC50	17 nM
6-(2,6-dichlorophenyl)-2-({4-[2-(diethylamino)ethoxy]phenyl}amino)-8-methyl-7H,8H-pyrido[2,3-d]pyrimidin-7-one	IC50	21 nM
PKC-412	KD	110 nM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	KD	120 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative
CHEMBL4075828	KD	128 nM
CHEMBL4067978	KD	444 nM
CHEMBL1908397	KD	650 nM
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide	KD	740 nM
(9S)-9-[(dimethylamino)methyl]-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-di(metheno)dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecine-18,20(19H)-dione	IC50	743 nM
Milciclib	IC50	1050 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol	KD	2400 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
SUNITINIB MALATE	KD	3500 nM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide	KD	3900 nM	US-20250129067: PLATELET-DERIVED GROWTH FACTOR RECEPTOR (PDGFR) ALPHA INHIBITORS AND USES THEREOF
(4-chlorophenyl)-[4-(4-pyridylmethyl)phthalazin-1-yl]amine	KD	8800 nM

ChEMBL bioactivities

21 potent at pChembl≥5 of 21 total, top 21 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.41	Kd	3.9	nM	ADAVOSERTIB
8.33	Kd	4.7	nM	CHEMBL4067978
8.30	Kd	5	nM	PD-0166285
7.58	Kd	26.6	nM	MILCICLIB
7.57	Kd	27	nM	ADAVOSERTIB
7.24	Kd	57	nM	CHEMBL386051
7.03	Kd	94	nM	BOSUTINIB
6.97	Kd	106	nM	BOSUTINIB
6.89	Kd	128	nM	PF-03814735
6.70	Kd	200	nM	DASATINIB
6.32	Kd	481	nM	DASATINIB
6.30	Kd	498	nM	PELITINIB
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.89	Kd	1300	nM	NERATINIB
5.38	Kd	4200	nM	TOZASERTIB
5.33	Kd	4700	nM	KW-2449
5.22	Kd	6000	nM	FEDRATINIB
5.10	Kd	7900	nM	LESTAURTINIB
5.03	Kd	9400	nM	R-406

PubChem BioAssay actives

18 with measured affinity, of 158 total; 15 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[6-(2-hydroxypropan-2-yl)-2-pyridinyl]-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	1450930: Binding affinity to recombinant human full-length N-terminal His8-tagged Wee2 (1 to 567 residues) expressed in human Expi293F cells assessed as dessociation constant by quantitative real-time PCR method	kd	0.0039	uM
4-(3,5-dichloro-4-methoxyanilino)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile	1450946: Binding affinity to recombinant human N-terminal His6-tagged Wee2 kinase domain (202 to 492 residues) expressed in Escherichia coli BL21 (DE3) by isothermal titration calorimetry	kd	0.0047	uM
6-(2,6-dichlorophenyl)-2-[4-[2-(diethylamino)ethoxy]anilino]-8-methylpyrido[2,3-d]pyrimidin-7-one	1450946: Binding affinity to recombinant human N-terminal His6-tagged Wee2 kinase domain (202 to 492 residues) expressed in Escherichia coli BL21 (DE3) by isothermal titration calorimetry	kd	0.0050	uM
N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide	1450946: Binding affinity to recombinant human N-terminal His6-tagged Wee2 kinase domain (202 to 492 residues) expressed in Escherichia coli BL21 (DE3) by isothermal titration calorimetry	kd	0.0266	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624746: Binding constant for WEE2 kinase domain	kd	0.0570	uM
Bosutinib	624746: Binding constant for WEE2 kinase domain	kd	0.0940	uM
N-[2-[(1R,8S)-4-[[4-(cyclobutylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-11-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-11-yl]-2-oxoethyl]acetamide	1450946: Binding affinity to recombinant human N-terminal His6-tagged Wee2 kinase domain (202 to 492 residues) expressed in Escherichia coli BL21 (DE3) by isothermal titration calorimetry	kd	0.1280	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	624746: Binding constant for WEE2 kinase domain	kd	0.2000	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	1450946: Binding affinity to recombinant human N-terminal His6-tagged Wee2 kinase domain (202 to 492 residues) expressed in Escherichia coli BL21 (DE3) by isothermal titration calorimetry	kd	0.4980	uM
Neratinib	624746: Binding constant for WEE2 kinase domain	kd	1.3000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	624746: Binding constant for WEE2 kinase domain	kd	4.2000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624746: Binding constant for WEE2 kinase domain	kd	4.7000	uM
Fedratinib	624746: Binding constant for WEE2 kinase domain	kd	6.0000	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	624746: Binding constant for WEE2 kinase domain	kd	7.9000	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624746: Binding constant for WEE2 kinase domain	kd	9.4000	uM

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1

ChEMBL screening assays

92 unique, capped per target: 92 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1059399	Binding	Inhibition of WEE2 assessed as enzyme activity at 1 uM relative to untreated control	Selective inhibitors of the mutant B-Raf pathway: discovery of a potent and orally bioavailable aminoisoquinoline. — *J Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for WEE2 across ~30M SureChEMBL compounds — explore on Sugi Predict.