Microcephaly 2, primary, autosomal recessive, with or without cortical malformations

Summary

Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (MONDO:0011435) is a disease caused by WDR62 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: WDR62 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 278

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 2, primary, autosomal recessive, with or without cortical malformations
Mondo ID	MONDO:0011435
MeSH	C565794
OMIM	604317
DOID	DOID:0070293
UMLS	C1858535
MedGen	346929
GARD	0015366
Is cancer (heuristic)	no

Also known as: MCPH2 · microcephaly 2, primary, autosomal recessive, with or without cortical malformations

Data availability: 278 ClinVar variants · 7 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive primary microcephaly › microcephaly 2, primary, autosomal recessive, with or without cortical malformations

Related subtypes (28): microcephaly 1, primary, autosomal recessive, microcephaly with simplified gyral pattern, microcephaly 4, primary, autosomal recessive, microcephaly 3, primary, autosomal recessive, microcephaly 5, primary, autosomal recessive, microcephaly 7, primary, autosomal recessive, microcephaly 8, primary, autosomal recessive, microcephaly 9, primary, autosomal recessive, microcephalic primordial dwarfism due to ZNF335 deficiency, microcephaly 11, primary, autosomal recessive, microcephaly 13, primary, autosomal recessive, microcephaly 12, primary, autosomal recessive, microcephaly 14, primary, autosomal recessive, microcephaly 15, primary, autosomal recessive, microcephaly 16, primary, autosomal recessive, microcephaly 17, primary, autosomal recessive, microcephaly 28, primary, autosomal recessive, microcephaly 29, primary, autosomal recessive, microcephaly 24, primary, autosomal recessive, microcephaly 25, primary, autosomal recessive, microcephaly 19, primary, autosomal recessive, microcephaly 20, primary, autosomal recessive, microcephaly 21, primary, autosomal recessive, microcephaly 22, primary, autosomal recessive, microcephaly 23, primary, autosomal recessive, microcephaly with or without short stature, microcephaly 30, primary, autosomal recessive, microcephaly 31, primary, autosomal recessive

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

278 retrieved; paginated sample, class counts are floors:

100 uncertain significance, 59 conflicting classifications of pathogenicity, 33 likely pathogenic, 30 pathogenic, 28 benign, 18 benign/likely benign, 8 pathogenic/likely pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1163628	NM_001083961.2(WDR62):c.2396_2397del (p.Glu799fs)	WDR62	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1187007	NM_001083961.2(WDR62):c.1234-1G>A	WDR62	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323767	NM_001083961.2(WDR62):c.198_201dup (p.Ile68fs)	WDR62	Pathogenic	criteria provided, single submitter
1327866	NM_001083961.2(WDR62):c.3462+1G>A	WDR62	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526085	NM_001083961.2(WDR62):c.250dup (p.His84fs)	WDR62	Pathogenic	criteria provided, single submitter
160260	NM_001083961.2(WDR62):c.2084_2090dup (p.Ser698fs)	WDR62	Pathogenic	criteria provided, single submitter
160272	NM_001083961.2(WDR62):c.2655C>G (p.Tyr885Ter)	WDR62	Pathogenic	criteria provided, single submitter
160282	NM_001083961.2(WDR62):c.332+1G>A	WDR62	Pathogenic	criteria provided, single submitter
1709550	NM_001083961.2(WDR62):c.1605dup (p.Glu536Ter)	WDR62	Pathogenic	criteria provided, single submitter
1805068	NM_001083961.2(WDR62):c.3863G>A (p.Trp1288Ter)	WDR62	Pathogenic	criteria provided, single submitter
1806268	NM_001083961.2(WDR62):c.2984C>G (p.Ser995Ter)	WDR62	Pathogenic	criteria provided, single submitter
1981207	NM_001083961.2(WDR62):c.3731_3740del (p.Thr1244fs)	WDR62	Pathogenic	criteria provided, multiple submitters, no conflicts
2434642	NM_001083961.2(WDR62):c.3322C>T (p.Gln1108Ter)	WDR62	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2442360	NM_001083961.2(WDR62):c.1175_1200dup (p.Leu401fs)	WDR62	Pathogenic	criteria provided, single submitter
2691894	NM_001083961.2(WDR62):c.2035-2A>G	WDR62	Pathogenic	criteria provided, single submitter
280634	NM_001083961.2(WDR62):c.1941C>A (p.Cys647Ter)	WDR62	Pathogenic	criteria provided, multiple submitters, no conflicts
31035	NM_001083961.2(WDR62):c.1313G>A (p.Arg438His)	WDR62	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31036	NM_001083961.2(WDR62):c.4241dup (p.Ser1415fs)	WDR62	Pathogenic	no assertion criteria provided
31037	NM_001083961.2(WDR62):c.1531G>A (p.Asp511Asn)	WDR62	Pathogenic	criteria provided, multiple submitters, no conflicts
31038	NM_001083961.2(WDR62):c.3936dup (p.Val1313fs)	WDR62	Pathogenic	criteria provided, single submitter
31039	NM_001083961.2(WDR62):c.363del (p.Asp122fs)	WDR62	Pathogenic	no assertion criteria provided
31040	NM_001083961.2(WDR62):c.193G>A (p.Val65Met)	WDR62	Pathogenic	no assertion criteria provided
31041	NM_001083961.2(WDR62):c.2086del (p.Ser696fs)	WDR62	Pathogenic	criteria provided, multiple submitters, no conflicts
31042	NM_001083961.2(WDR62):c.2746_2747del (p.Gln918fs)	WDR62	Pathogenic	criteria provided, multiple submitters, no conflicts
3677924	NM_001083961.2(WDR62):c.1534C>T (p.Arg512Ter)	WDR62	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
40	NM_001083961.2(WDR62):c.4205_4208del (p.Val1402fs)	WDR62	Pathogenic	no assertion criteria provided
42	NM_001083961.2(WDR62):c.671G>C (p.Trp224Ser)	WDR62	Pathogenic	no assertion criteria provided
43	NM_001083961.2(WDR62):c.1408C>T (p.Gln470Ter)	WDR62	Pathogenic	no assertion criteria provided
437291	NM_001083961.2(WDR62):c.3514+1G>A	WDR62	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
437292	NM_001083961.2(WDR62):c.3012_3034dup (p.Pro1012fs)	WDR62	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
WDR62	Definitive	Autosomal recessive	microcephaly 2, primary, autosomal recessive, with or without cortical malformations	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WDR62	Orphanet:2512	Autosomal recessive primary microcephaly

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
WDR62	HGNC:24502	ENSG00000075702	O43379	WD repeat-containing protein 62	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WDR62	WD repeat-containing protein 62	Required for cerebral cortical development.

Protein-family classification

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

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WDR62	Scaffold/PPI	no		WD40_rpt, Quinoprotein_ADH-like_sf, WD40/YVTN_repeat-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
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WDR62	211	ubiquitous	marker	left testis, right testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WDR62	1,414

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WDR62	O43379	61.19

Function

Pathway analysis

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

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of centrosome cycle	1	1872.4×	0.003	WDR62
positive regulation of neuron migration	1	991.3×	0.003	WDR62
centriole replication	1	732.7×	0.003	WDR62
regulation of neuron differentiation	1	732.7×	0.003	WDR62
positive regulation of neuroblast proliferation	1	581.1×	0.003	WDR62
mitotic spindle organization	1	271.8×	0.005	WDR62
neurogenesis	1	208.1×	0.005	WDR62
cerebral cortex development	1	205.5×	0.005	WDR62

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
WDR62	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	WDR62

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
WDR62	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.