WDR62

Summary

WDR62 (WD repeat domain 62, HGNC:24502) is a protein-coding gene on chromosome 19q13.12, encoding WD repeat-containing protein 62 (O43379). Required for cerebral cortical development.

This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and cognitive disability. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 284403 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly 2, primary, autosomal recessive, with or without cortical malformations (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 1,175 total — 63 pathogenic, 51 likely-pathogenic
• Phenotypes (HPO): 54
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001083961

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24502
Approved symbol	WDR62
Name	WD repeat domain 62
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434J046, FLJ33298
Ensembl gene	ENSG00000075702
Ensembl biotype	protein_coding
OMIM	613583
Entrez	284403

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 15 protein_coding, 15 nonsense_mediated_decay, 10 retained_intron

ENST00000270301, ENST00000378860, ENST00000401500, ENST00000427823, ENST00000587391, ENST00000589953, ENST00000608676, ENST00000644764, ENST00000679357, ENST00000679422, ENST00000679489, ENST00000679598, ENST00000679682, ENST00000679714, ENST00000679757, ENST00000679858, ENST00000680211, ENST00000680280, ENST00000680321, ENST00000680349, ENST00000680359, ENST00000680377, ENST00000680403, ENST00000680489, ENST00000680564, ENST00000680590, ENST00000680597, ENST00000680739, ENST00000680773, ENST00000680806, ENST00000680858, ENST00000680997, ENST00000681088, ENST00000681302, ENST00000681542, ENST00000681597, ENST00000681608, ENST00000681625, ENST00000681648, ENST00000681809

RefSeq mRNA: 5 — MANE Select: NM_001083961 NM_001083961, NM_001411145, NM_001411146, NM_001411147, NM_173636

CCDS: CCDS33001, CCDS46059, CCDS92602, CCDS92603, CCDS92604

Canonical transcript exons

ENST00000401500 — 32 exons

Exon	Start	End
ENSE00000953242	36101214	36101317
ENSE00000953243	36101664	36101774
ENSE00000953244	36102014	36102151
ENSE00001429991	36081433	36081570
ENSE00001563405	36102737	36102851
ENSE00002840571	36054897	36055148
ENSE00003458319	36086687	36086812
ENSE00003472665	36089185	36089306
ENSE00003523950	36094031	36094164
ENSE00003524948	36099399	36099617
ENSE00003527065	36090445	36090520
ENSE00003545232	36104518	36104675
ENSE00003547966	36103343	36103981
ENSE00003564014	36097027	36097079
ENSE00003588856	36089038	36089105
ENSE00003598245	36103156	36103207
ENSE00003604680	36091402	36091465
ENSE00003613990	36083063	36083241
ENSE00003617275	36091200	36091311
ENSE00003632517	36092689	36092811
ENSE00003645193	36102948	36103074
ENSE00003683636	36100748	36100875
ENSE00003686763	36084653	36084744
ENSE00003697091	36066257	36066427
ENSE00003697155	36073342	36073531
ENSE00003697976	36067306	36067443
ENSE00003699148	36058780	36058871
ENSE00003700548	36065958	36066015
ENSE00003701607	36067828	36068010
ENSE00003702285	36059968	36060030
ENSE00003702328	36071556	36071716
ENSE00003842243	36104768	36105108

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 95.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4271 / max 274.7108, expressed in 1293 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175453	7.2016	1143
175454	2.1929	671
175462	0.2871	155
175456	0.2663	42
175459	0.2061	23
175457	0.0818	34
175460	0.0638	15
175461	0.0591	12
175463	0.0431	16
175458	0.0254	12

Top tissues by expression

267 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	95.52	gold quality
right testis	UBERON:0004534	95.48	gold quality
testis	UBERON:0000473	91.76	gold quality
apex of heart	UBERON:0002098	90.50	gold quality
diaphragm	UBERON:0001103	89.94	silver quality
triceps brachii	UBERON:0001509	89.27	gold quality
vastus lateralis	UBERON:0001379	88.95	silver quality
quadriceps femoris	UBERON:0001377	87.68	silver quality
hindlimb stylopod muscle	UBERON:0004252	87.25	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.54	gold quality
biceps brachii	UBERON:0001507	84.94	gold quality
gluteal muscle	UBERON:0002000	84.09	silver quality
skeletal muscle tissue	UBERON:0001134	84.02	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.97	gold quality
muscle tissue	UBERON:0002385	82.06	gold quality
male germ cell	CL:0000015	81.83	gold quality
sperm	CL:0000019	81.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.46	gold quality
ventricular zone	UBERON:0003053	80.86	gold quality
muscle organ	UBERON:0001630	80.60	gold quality
heart left ventricle	UBERON:0002084	80.45	gold quality
myocardium	UBERON:0002349	80.18	silver quality
cardiac ventricle	UBERON:0002082	80.11	gold quality
left ventricle myocardium	UBERON:0006566	78.82	silver quality
buccal mucosa cell	CL:0002336	78.43	gold quality
muscle of leg	UBERON:0001383	78.36	gold quality
oocyte	CL:0000023	77.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.82	gold quality
gastrocnemius	UBERON:0001388	77.32	gold quality
ganglionic eminence	UBERON:0004023	77.10	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	8.62
E-ANND-3	yes	5.83

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• JNK and WDR62 may regulate the dynamic interplay between polysomes stress granule and processing bodies, thereby mediating mRNA fate after stress. (PMID:19910486)
• Study demonstrates the use of whole-exome sequencing to identify recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly. (PMID:20729831)
• The diverse phenotypes of WDR62 suggest it has central roles in many aspects of cerebral cortical development and that mutations cause microencephaly. (PMID:20890278)
• Identification of WDR62 as the second most common cause of second most common cause of autosoml reccessive microcephaly. (PMID:20890279)
• WDR62 mutations found in individuals with microcephaly associated with a broad range of malformations of cortical development. (PMID:20980985)
• Homozygous mutations in WDR62 cause autosomal recessive primary microcephaly in families linked to the MCPH2 locus. This gene encodes a centrosomal as well as nuclear protein. (PMID:21496009)
• Mutations in WDR62 gene leads to microcephaly and other brain malformations. (PMID:21496009)
• The docking domain of WDR62 interacts with all JNK isoforms through a D domain motif located at the C-terminus. (PMID:21749326)
• study reports using whole-exome sequencing to identify compound heterozygous mutations in the WD repeat domain 62 (WDR62) gene as the cause of recurrent polymicrogyria in a sibling pair (PMID:21834044)
• data indicate that WDR62 mutations cause about 4% of autosomal recessive primary microcephaly in Pakistan. (PMID:21961505)
• homozygous missense mutation in WDR62, p.E400K, was found in both boys and segregated with the condition in this family. WDR62 is one of seven genes responsible for autosomal recessive primary microcephaly (PMID:22308068)
• A homozygous deletion mutation c.1143delA was detected in exon 9 of WDR62 gene, in all affected individuals with primary microcephaly in a Pakistani family, which resulted in frameshift and protein truncation (p.H381PfsX48). (PMID:23065275)
• Data indicate that WDR62 dimerization is required for JNK2 and MKK7beta1 recruitment. (PMID:23341463)
• WDR62 may be a novel prognostic marker and a potential chemotherapy target for gastric cancer. (PMID:23920402)
• Abnormal centrosome and spindle morphology in a patient with autosomal recessive primary microcephaly type 2 due to compound heterozygous WDR62 gene mutation (PMID:24228726)
• WDR62 controls neurogenesis through JNK signaling in rat model. (PMID:24388750)
• Genetic factors contribute to modify the severity of the WDR62 phenotype. (PMID:24842779)
• Data show that CUL4B variants are associated with a wide range of cerebral malformations and suggest an important role in brain through its interaction with WDR62, a protein in which variants were identified in patients with cerebral malformations. (PMID:25385192)
• The results confirm that mutations in ASPM or WDR62 are the major cause of autosomal recessive primary microcephaly in the Pakistani population. (PMID:27784895)
• Case Report: WDR62 missence mutations associated with early onset acanthosis and hyperkeratosis in a patient with autosomal recessive microcephaly type 2. (PMID:27852057)
• Our findings demonstrate critical and diverse functions of WDR62 in neocortical development and provide insight into the mechanisms by which its disruption leads to a plethora of structural abnormalities. (PMID:28272472)
• WDR62-overexpressing lung cancer cells exhibited an increase in cell growth. Moreover, the concurrent overexpression of WDR62 and TPX2, a WDR62-interacting protein that is also overexpressed in lung adenocarcinoma, induced centrosome amplification in the lung cells. (PMID:28277612)
• A novel WDR62 missense mutation causes primary microcephaly in a large consanguineous Saudi family (PMID:28377545)
• We report a clinical feature, electroclinical findings, and clinical course of a patient with a severe phenotype of MCPH2 including microcephaly, refractory infantile spasms and intellectual disability. We detected a new homozygous splicing variant c.3335+1G>C in the WD repeat domain 62 (WDR62) gene, and an additional new heterozygous missense mutation c.1706T>A of G protein-coupled receptor 56 (GPR56) gene (PMID:28756000)
• Authors demonstrated that WDR62 is a PLK1 substrate that is phosphorylated at Ser 897, and that this phosphorylation at the spindle poles promotes astral microtubule assembly to stabilize spindle orientation. (PMID:28973348)
• Exome sequencing led to the rapid and cost-effective identification of a novel homozygous mutation in WDR62 gene. (PMID:30021525)
• WDR62 coordinates the TNFalpha receptor signaling pathway to JNK activation through association with multiple kinases and the adaptor protein TRAF2. (PMID:30091641)
• Wdr62 is involved in meiotic initiation via activating JNK signaling, which displays a novel mechanism for regulating meiotic initiation, and mutation of WDR62 is one of the potential etiologies of premature ovarian insufficiency in humans. (PMID:30102701)
• Haplotype analysis showed genetic relatedness between the families of the patients. Our findings expand the spectrum of mutations randomly distributed in the WDR62 gene. A review is also provided of the brain malformations described in WDR62 mutations in association with congenital microcephaly (PMID:30706430)
• relative WDR62 mRNA expression was not statistically different in differentiated thyroid carcinoma tissues and goiter tissues (PMID:30884127)
• The expression levels of miR223 were significantly decreased in clinical bladder cancer (BC) specimens. The restoration of miR223 expression significantly inhibited tumor aggressiveness and induced apoptosis in BC cells. Direct binding between oncogenic WDR62 and miR223 was confirmed by luciferase assay. The knockdown of WDR62 significantly inhibited tumor aggressiveness and induced the apoptosis of BC cells. (PMID:30942440)
• Study in mutant mice and human cerebral organoids showed that WDR62 deletion resulted in a reduction in the size of mouse brains and organoids due to the disruption of neural progenitor cells. WDR62 interacts with and promotes CEP170 localization to the basal body of primary cilium, where CEP170 recruits KIF2A to disassemble cilium. (PMID:31197141)
• Further Delineation of Phenotype and Genotype of Primary Microcephaly Syndrome with Cortical Malformations Associated with Mutations in the WDR62 Gene. (PMID:33921653)
• WDR62 localizes katanin at spindle poles to ensure synchronous chromosome segregation. (PMID:34137788)
• WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin. (PMID:34137789)
• Systematic Analysis of the Oncogenic Role of WDR62 in Human Tumors. (PMID:34306258)
• An integrated functional and clinical genomics approach reveals genes driving aggressive metastatic prostate cancer. (PMID:34326322)
• Neurological outcome in WDR62 primary microcephaly. (PMID:35726608)
• WDR62 variants contribute to congenital heart disease by inhibiting cardiomyocyte proliferation. (PMID:35808830)
• Molecular genetics, neuroimaging outcomes, and structural analyses of novel and recurrent variants of WDR62 gene in two consanguineous Pakistani families with autosomal recessive primary microcephaly. (PMID:38926176)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Wdr62	ENSMUSG00000037020
rattus_norvegicus	Wdr62	ENSRNOG00000020807

Paralogs (26): PAFAH1B1 (ENSG00000007168), SNRNP40 (ENSG00000060688), WDR7 (ENSG00000091157), TBL2 (ENSG00000106638), PAK1IP1 (ENSG00000111845), WDR75 (ENSG00000115368), DCAF4 (ENSG00000119599), DAW1 (ENSG00000123977), TEP1 (ENSG00000129566), AHI1 (ENSG00000135541), WDR38 (ENSG00000136918), MAPKBP1 (ENSG00000137802), POC1B (ENSG00000139323), NEDD1 (ENSG00000139350), COP1 (ENSG00000143207), WDR17 (ENSG00000150627), WDR43 (ENSG00000163811), POC1A (ENSG00000164087), WDR88 (ENSG00000166359), WDR81 (ENSG00000167716), DCAF4L2 (ENSG00000176566), DCAF4L1 (ENSG00000182308), WDR27 (ENSG00000184465), NWD1 (ENSG00000188039), WDR5 (ENSG00000196363), WDR5B (ENSG00000196981)

Protein

Protein identifiers

WD repeat-containing protein 62 — O43379 (reviewed: O43379)

All UniProt accessions (26): O43379, A0A2R8YD43, A0A7P0T846, A0A7P0T8C3, A0A7P0T8C4, A0A7P0T8R7, A0A7P0T8U8, A0A7P0T8V3, A0A7P0T8Z9, A0A7P0T972, A0A7P0T975, A0A7P0T9D9, A0A7P0T9F6, A0A7P0T9G3, A0A7P0T9T4, A0A7P0T9T7, A0A7P0TA81, A0A7P0TA99, A0A7P0TAH3, A0A7P0TAK3, A0A7P0TB98, A0A7P0TBE7, A0A7P0Z429, A0A7P0Z436, A0A7P0Z438, H7C3R4

UniProt curated annotations — full annotation on UniProt →

Function. Required for cerebral cortical development. Plays a role in neuronal proliferation and migration. Plays a role in mother-centriole-dependent centriole duplication; the function also seems to involve CEP152, CDK5RAP2 and CEP63 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication.

Subunit / interactions. Can form homodimers (via C-terminus). Interacts (via C-terminus) with MAPKBP1 (via C-terminus). Interacts with CDK5RAP2, CEP152, CEP63 and KIAA0753. CEP63, CDK5RAP2, CEP152, WDR62 are proposed to form a stepwise assembled complex at the centrosome forming a ring near parental centrioles.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Spindle pole. Microtubule organizing center. Centrosome. Centriole.

Tissue specificity. Present in fetal brain, enriched within the ventricular and subventricular zone (at protein level). In the embryonic brain it is expressed in mitotic neural precursor cells.

Disease relevance. Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (MCPH2) [MIM:604317] A disease characterized by microcephaly, moderate to severe intellectual disability, and various type of cortical malformations in most patients. Microcephaly is defined as a head circumference more than 3 standard deviations below the age-related mean. Cortical malformations include pachygyria with cortical thickening, microgyria, lissencephaly, hypoplasia of the corpus callosum, schizencephaly. All affected individuals have delayed psychomotor development. Some patients have seizures. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (4)

UniProt ID	Names	Canonical?
O43379-1	1	yes
O43379-2	2
O43379-3	3
O43379-4	4

RefSeq proteins (5): NP_001077430, NP_001398074, NP_001398075, NP_001398076, NP_775907 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR011047	Quinoprotein_ADH-like_sf	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR052779	WDR62	Family
IPR056161	WD40_MABP1-WDR62_1st	Domain
IPR056162	WD40_MABP1-WDR62_2nd	Domain
IPR056364	WDR62-MABP1_CC	Domain

Pfam: PF24780, PF24782, PF24795

UniProt features (65 total): modified residue 18, repeat 15, sequence variant 12, compositionally biased region 7, splice variant 5, region of interest 4, sequence conflict 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43379-F1	61.19	0.35

Functional residue map

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

Post-translational modifications (18): 2, 33, 46, 49, 50, 52, 501, 944, 1053, 1070, 1093, 1101, 1123, 1144, 1228, 1248, 1249, 1268

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 334 (showing top): MORF_RAGE, E2F_Q4, MYAATNNNNNNNGGC_UNKNOWN, E2F_Q4_01, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, E2F4DP1_01, MORF_ATRX, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NEUROBLAST_PROLIFERATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION

GO Biological Process (9): positive regulation of neuroblast proliferation (GO:0002052), mitotic spindle organization (GO:0007052), centriole replication (GO:0007099), cerebral cortex development (GO:0021987), neurogenesis (GO:0022008), regulation of neuron differentiation (GO:0045664), regulation of centrosome cycle (GO:0046605), positive regulation of neuron migration (GO:2001224), nervous system development (GO:0007399)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (8): spindle pole (GO:0000922), nucleus (GO:0005634), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), centriolar satellite (GO:0034451), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
microtubule organizing center	2
intracellular membraneless organelle	2
neuroblast proliferation	1
positive regulation of neurogenesis	1
regulation of neuroblast proliferation	1
positive regulation of neural precursor cell proliferation	1
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
cell cycle process	1
centrosome duplication	1
centriole assembly	1
pallium development	1
anatomical structure development	1
nervous system development	1
cell differentiation	1
neuron differentiation	1
regulation of cell differentiation	1
centrosome cycle	1
regulation of cell cycle process	1
regulation of microtubule-based process	1
regulation of cellular component organization	1
neuron migration	1
positive regulation of cell migration	1
regulation of neuron migration	1
system development	1
binding	1
spindle	1
intracellular membrane-bounded organelle	1
centriole	1
cytoplasm	1
centrosome	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1066 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR62	ASPM	Q8IZT6	951
WDR62	CEP63	Q96MT8	849
WDR62	CDK5RAP2	Q96SN8	846
WDR62	CPAP	Q9HC77	823
WDR62	MCPH1	Q8NEM0	820
WDR62	STIL	Q15468	813
WDR62	MAP2K7	O14733	810
WDR62	CEP135	Q66GS9	768
WDR62	EOMES	O95936	762
WDR62	CEP152	O94986	720
WDR62	ZNF335	Q9H4Z2	691
WDR62	RTTN	Q86VV8	633
WDR62	NDE1	Q9NXR1	627
WDR62	ANKLE2	Q86XL3	612
WDR62	SASS6	Q6UVJ0	602

IntAct

162 interactions, top by confidence:

A	B	Type	Score
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
WDR62	MAPK9	psi-mi:“MI:0915”(physical association)	0.800
MAPK9	WDR62	psi-mi:“MI:0914”(association)	0.800
MAPK9	WDR62	psi-mi:“MI:0915”(physical association)	0.800
YWHAB	WDR62	psi-mi:“MI:0914”(association)	0.770
MAPK8	WDR62	psi-mi:“MI:0914”(association)	0.730
YWHAH	FAM83G	psi-mi:“MI:0914”(association)	0.710
GABARAPL2	IPO5	psi-mi:“MI:0914”(association)	0.690
WDR62	ENKD1	psi-mi:“MI:0915”(physical association)	0.670
CEP170	KIF2A	psi-mi:“MI:2364”(proximity)	0.650
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
WDR62	YWHAE	psi-mi:“MI:0915”(physical association)	0.600
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
WDR62	MAGEB4	psi-mi:“MI:0915”(physical association)	0.560
WDR62	P4HA3	psi-mi:“MI:0915”(physical association)	0.560
DYRK2	WDR62	psi-mi:“MI:0915”(physical association)	0.560
WDR62	TBC1D23	psi-mi:“MI:0915”(physical association)	0.560
TBC1D23	WDR62	psi-mi:“MI:0915”(physical association)	0.560
P4HA3	WDR62	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (186): WDR62 (Two-hybrid), WDR62 (Two-hybrid), WDR62 (Two-hybrid), WDR62 (Two-hybrid), WDR62 (Two-hybrid), WDR62 (Affinity Capture-MS), WDR62 (Affinity Capture-MS), WDR62 (Two-hybrid), WDR62 (Affinity Capture-MS), WDR62 (Affinity Capture-MS), WDR62 (Proximity Label-MS), WDR62 (Proximity Label-MS), WDR62 (Proximity Label-MS), KIFC3 (Affinity Capture-MS), PDE3A (Affinity Capture-MS)

ESM2 similar proteins: A0A1L1SUL6, F1LQY6, O35465, O43379, O75293, O88910, O88954, P0C0T1, P21964, P22339, P41214, P50747, Q13368, Q13572, Q14318, Q16342, Q1HAQ0, Q28955, Q2T9Z1, Q3B7U9, Q3TFD2, Q3TMX7, Q496Y0, Q4AC99, Q5BIM1, Q5E9A5, Q5R812, Q5RA63, Q5SZD4, Q64311, Q6DC64, Q6P5G6, Q6PFY8, Q80YV4, Q8BNV1, Q8BYN3, Q8NFZ0, Q8R1C6, Q8R1T1, Q8TCU6

Diamond homologs: O43379, O60336, Q3U3T8, Q6DFF9, Q6NS57, Q8HXL3, Q9AV81, Q6CG48, A1CF18, A8NWR2, A8X8C6, B2AEZ5, O14011, O14053, O22785, O75083, O88342, P27612, P42935, P54319, Q08924, Q08E38, Q0U1B1, Q10051, Q17963, Q2HBX6, Q2KJH4, Q39336, Q54MH6, Q54ZP5, Q5ZL33, Q5ZMA2, Q6GM65, Q7KWK5, Q8RXA7, Q94BR4, Q99KP6, Q9C270, Q9JHB4, Q9JMJ4

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
MAPK8	“down-regulates quantity by destabilization”	WDR62	phosphorylation
FBXO7	“down-regulates quantity by destabilization”	WDR62	ubiquitination
CDK5RAP2	“up-regulates activity”	WDR62	relocalization
WDR62	“up-regulates activity”	CDK2	relocalization
WDR62	“up-regulates activity”	MAP2K4	relocalization
WDR62	“up-regulates activity”	MAP2K7	relocalization
WDR62	“up-regulates activity”	MAP3K3	relocalization
WDR62	“up-regulates activity”	MAPK8	relocalization
AURKA	“up-regulates activity”	WDR62	phosphorylation
MAP3K3	“up-regulates quantity by stabilization”	WDR62	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	67.2×	2e-11
Activation of BAD and translocation to mitochondria	7	66.6×	4e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	58.8×	7e-10
Activation of BH3-only proteins	8	49.6×	2e-10
Intrinsic Pathway for Apoptosis	8	29.3×	8e-09
RHO GTPases activate PKNs	7	27.8×	1e-07
Centrosome maturation	7	22.2×	4e-07
FOXO-mediated transcription	5	21.0×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	5	31.6×	8e-05
protein targeting	7	22.1×	2e-05
establishment of mitotic spindle orientation	5	20.8×	5e-04
mitotic spindle organization	5	11.7×	5e-03
regulation of circadian rhythm	5	11.2×	5e-03
rhythmic process	5	10.8×	6e-03
intracellular protein localization	10	9.0×	5e-05
microtubule cytoskeleton organization	8	8.4×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1175 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	63
Likely pathogenic	51
Uncertain significance	493
Likely benign	333
Benign	82

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1180671	NM_001083961.2(WDR62):c.1319G>A (p.Trp440Ter)	Pathogenic
1323767	NM_001083961.2(WDR62):c.198_201dup (p.Ile68fs)	Pathogenic
1326511	NM_001083961.2(WDR62):c.640_642delinsTT (p.Val214fs)	Pathogenic
1338552	NM_001083961.1(WDR62):c.1959_1960del	Pathogenic
1362663	NM_001083961.2(WDR62):c.2864_2867del (p.Asp955fs)	Pathogenic
1429461	NM_001083961.2(WDR62):c.731C>T (p.Ser244Leu)	Pathogenic
1456076	NM_001083961.2(WDR62):c.2111C>A (p.Ser704Ter)	Pathogenic
1526085	NM_001083961.2(WDR62):c.250dup (p.His84fs)	Pathogenic
160260	NM_001083961.2(WDR62):c.2084_2090dup (p.Ser698fs)	Pathogenic
160272	NM_001083961.2(WDR62):c.2655C>G (p.Tyr885Ter)	Pathogenic
160282	NM_001083961.2(WDR62):c.332+1G>A	Pathogenic
1709550	NM_001083961.2(WDR62):c.1605dup (p.Glu536Ter)	Pathogenic
1801978	NM_001083961.2(WDR62):c.3462+1G>C	Pathogenic
1805068	NM_001083961.2(WDR62):c.3863G>A (p.Trp1288Ter)	Pathogenic
1806268	NM_001083961.2(WDR62):c.2984C>G (p.Ser995Ter)	Pathogenic
1981207	NM_001083961.2(WDR62):c.3731_3740del (p.Thr1244fs)	Pathogenic
2053008	NM_001083961.2(WDR62):c.557G>A (p.Trp186Ter)	Pathogenic
208910	NM_001083961.2(WDR62):c.2030T>C (p.Leu677Pro)	Pathogenic
2105768	NM_001083961.2(WDR62):c.800dup (p.Ser268fs)	Pathogenic
2295417	NM_001083961.2(WDR62):c.3124G>T (p.Gly1042Ter)	Pathogenic
242539	NM_001083961.2(WDR62):c.3304C>T (p.Gln1102Ter)	Pathogenic
2442360	NM_001083961.2(WDR62):c.1175_1200dup (p.Leu401fs)	Pathogenic
2582970	NM_001083961.2(WDR62):c.600_601del (p.Arg200fs)	Pathogenic
2582974	GRCh37/hg19 19q13.12(chr19:36572335-36574143)x3	Pathogenic
2662408	NM_001083961.2(WDR62):c.1777_1778del (p.Asp593fs)	Pathogenic
2691894	NM_001083961.2(WDR62):c.2035-2A>G	Pathogenic
280634	NM_001083961.2(WDR62):c.1941C>A (p.Cys647Ter)	Pathogenic
280706	NM_001083961.2(WDR62):c.2467+2T>G	Pathogenic
2814429	NM_001083961.2(WDR62):c.3454_3455del (p.Arg1152fs)	Pathogenic
2846612	NM_001083961.2(WDR62):c.2091del (p.Ser698fs)	Pathogenic

SpliceAI

4766 predictions. Top by Δscore:

Variant	Effect	Δscore
19:36055147:GG:G	donor_gain	1.0000
19:36055148:GG:G	donor_gain	1.0000
19:36055148:GGTG:G	donor_loss	1.0000
19:36055149:G:GG	donor_gain	1.0000
19:36058774:TTGCA:T	acceptor_loss	1.0000
19:36058775:TGCA:T	acceptor_loss	1.0000
19:36058776:GCA:G	acceptor_loss	1.0000
19:36058777:CAGG:C	acceptor_loss	1.0000
19:36058778:A:AG	acceptor_gain	1.0000
19:36058778:AG:A	acceptor_gain	1.0000
19:36058778:AGGT:A	acceptor_gain	1.0000
19:36058778:AGGTG:A	acceptor_loss	1.0000
19:36058779:G:GT	acceptor_gain	1.0000
19:36058779:GG:G	acceptor_gain	1.0000
19:36058779:GGT:G	acceptor_gain	1.0000
19:36058779:GGTG:G	acceptor_gain	1.0000
19:36058779:GGTGT:G	acceptor_gain	1.0000
19:36058867:GCAGG:G	donor_gain	1.0000
19:36058868:CAGGG:C	donor_loss	1.0000
19:36058869:AGGGT:A	donor_loss	1.0000
19:36058870:GG:G	donor_gain	1.0000
19:36058871:GG:G	donor_gain	1.0000
19:36058871:GGTA:G	donor_loss	1.0000
19:36058872:G:GG	donor_gain	1.0000
19:36058872:GTA:G	donor_loss	1.0000
19:36058880:A:G	donor_gain	1.0000
19:36059964:CCAGC:C	acceptor_loss	1.0000
19:36059966:A:AG	acceptor_gain	1.0000
19:36059966:AGCT:A	acceptor_gain	1.0000
19:36059967:G:GA	acceptor_gain	1.0000

AlphaMissense

9951 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:36066010:G:T	G129W	1.000
19:36066279:G:C	R138P	1.000
19:36066284:T:A	W140R	1.000
19:36066284:T:C	W140R	1.000
19:36066416:T:A	W184R	1.000
19:36066416:T:C	W184R	1.000
19:36067385:T:A	V214D	1.000
19:36067414:T:A	W224R	1.000
19:36067414:T:C	W224R	1.000
19:36083214:C:A	A508D	1.000
19:36086717:A:C	D558A	1.000
19:36086717:A:T	D558V	1.000
19:36086720:G:C	R559P	1.000
19:36086723:T:C	L560P	1.000
19:36089061:A:C	S598R	1.000
19:36089063:C:A	S598R	1.000
19:36089063:C:G	S598R	1.000
19:36089073:G:C	D602H	1.000
19:36089074:A:T	D602V	1.000
19:36089297:G:C	R650P	1.000
19:36091231:C:A	A689D	1.000
19:36091450:C:A	T732K	1.000
19:36091450:C:G	T732R	1.000
19:36092702:T:A	W742R	1.000
19:36092702:T:C	W742R	1.000
19:36058859:C:A	A86D	0.999
19:36066008:C:A	T128K	0.999
19:36066011:G:A	G129E	0.999
19:36066270:C:A	P135H	0.999
19:36066276:T:A	V137E	0.999

dbSNP variants (sampled 300 via entrez): RS1000037290 (19:36064733 A>G), RS1000042892 (19:36068941 G>A), RS1000075891 (19:36078217 C>G,T), RS1000137083 (19:36106580 A>C,G), RS1000211156 (19:36067087 T>C), RS1000242418 (19:36066721 G>A), RS1000269388 (19:36105625 T>C), RS1000335593 (19:36101038 G>A,C), RS1000388658 (19:36061579 G>A), RS1000389737 (19:36079137 A>C), RS1000402134 (19:36063216 T>G), RS1000421665 (19:36072055 C>G), RS1000447202 (19:36078785 A>C,G), RS1000539010 (19:36108970 T>C), RS1000570397 (19:36055198 C>G,T)

Disease associations

OMIM: gene MIM:613583 | disease phenotypes: MIM:604317, MIM:617616, MIM:251200, MIM:610805

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly 2, primary, autosomal recessive, with or without cortical malformations	Definitive	Autosomal recessive
autosomal recessive primary microcephaly	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
microcephaly 2, primary, autosomal recessive, with or without cortical malformations	Definitive	AR

Mondo (9): microcephaly 2, primary, autosomal recessive, with or without cortical malformations (MONDO:0011435), congenital nervous system disorder (MONDO:0002320), Skraban-Deardorff syndrome (MONDO:0054636), intellectual disability (MONDO:0001071), autosomal recessive primary microcephaly (MONDO:0016660), congenital heart disease (MONDO:0005453), congenital anomaly of kidney and urinary tract (MONDO:0019719), microcephaly 1, primary, autosomal recessive (MONDO:0009617), microcephaly (MONDO:0001149)

Orphanet (5): Autosomal recessive primary microcephaly (Orphanet:2512), Intellectual disability-seizures-abnormal gait-facial dysmorphism syndrome (Orphanet:513456), Renal or urinary tract malformation (Orphanet:93545), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), Premature chromosome condensation with microcephaly and intellectual disability (Orphanet:52183)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000122	Unilateral renal agenesis
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000303	Mandibular prognathia
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000414	Bulbous nose
HP:0000582	Upslanted palpebral fissure
HP:0000718	Aggressive behavior
HP:0000742	Self-mutilation
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001269	Hemiparesis
HP:0001270	Motor delay
HP:0001274	Agenesis of corpus callosum
HP:0001276	Hypertonia
HP:0001285	Spastic tetraparesis
HP:0001302	Pachygyria
HP:0001339	Lissencephaly
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001508	Failure to thrive
HP:0001510	Growth delay

GWAS associations

0 associations (top):

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C579935	Autosomal Recessive Primary Microcephaly (supp.)
C566906	Cakut (supp.)
C565384	Microcephaly, Primary Autosomal Recessive, 1 (supp.)
C565794	Microcephaly, Primary Autosomal Recessive, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	3
Aflatoxin B1	increases expression, increases methylation, decreases methylation	3
arsenite	affects localization, affects binding, decreases reaction	2
aristolochic acid I	increases expression	1
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	decreases expression	1
glycidyl methacrylate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
cupric chloride	increases expression	1
coumarin	increases phosphorylation	1
diallyl trisulfide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
abrine	increases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	affects phosphorylation	1
Calcitriol	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

198 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability