Microcephaly 9, primary, autosomal recessive

Summary

Microcephaly 9, primary, autosomal recessive (MONDO:0013923) is a disease caused by CEP152 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CEP152 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 177

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 9, primary, autosomal recessive
Mondo ID	MONDO:0013923
OMIM	614852
DOID	DOID:0070292
UMLS	C3553886
MedGen	766800
GARD	0015855
Is cancer (heuristic)	no

Also known as: autosomal recessive primary microcephaly caused by mutation in CEP152 · CEP152 autosomal recessive primary microcephaly · MCPH9 · microcephaly 9, primary, autosomal recessive

Data availability: 177 ClinVar variants · 1 GenCC gene-disease record.

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 9, primary, autosomal recessive

Related subtypes (28): microcephaly 1, primary, autosomal recessive, microcephaly with simplified gyral pattern, microcephaly 2, primary, autosomal recessive, with or without cortical malformations, 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, 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

177 retrieved; paginated sample, class counts are floors:

67 uncertain significance, 49 conflicting classifications of pathogenicity, 17 pathogenic/likely pathogenic, 14 benign, 10 likely pathogenic, 10 benign/likely benign, 9 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
446758	NM_001194998.1(CEP152):c.[3676_3678delAAC;3149T>C]		Pathogenic	no assertion criteria provided
1069366	NM_001194998.2(CEP152):c.2318G>A (p.Trp773Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1186425	NM_001194998.2(CEP152):c.467dup (p.Gln157fs)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324054	NM_001194998.2(CEP152):c.540+1G>A	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
158223	NM_001194998.2(CEP152):c.1155del (p.Thr386fs)	CEP152	Pathogenic	criteria provided, multiple submitters, no conflicts
158240	NM_001194998.2(CEP152):c.2034T>G (p.Tyr678Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
158244	NM_001194998.2(CEP152):c.2679del (p.Ser894fs)	CEP152	Pathogenic	criteria provided, single submitter
158250	NM_001194998.2(CEP152):c.3016del (p.Thr1006fs)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1676669	NM_001194998.2(CEP152):c.2034_2036del (p.Tyr678_Gln679delinsTer)	CEP152	Pathogenic	criteria provided, multiple submitters, no conflicts
1709492	NM_001194998.2(CEP152):c.3948_3949insGGCGCAAATATTATTTG (p.Ile1317delinsGlyAlaAsnIleIleTer)	CEP152	Pathogenic	criteria provided, single submitter
210686	NM_001194998.2(CEP152):c.3014_3015delinsT (p.Lys1005fs)	CEP152	Pathogenic	criteria provided, single submitter
2189940	NM_001194998.2(CEP152):c.799C>T (p.Arg267Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2636246	NM_001194998.2(CEP152):c.3172del (p.Gln1058fs)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2715024	NM_001194998.2(CEP152):c.903_904del (p.Glu301fs)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2784802	NM_001194998.2(CEP152):c.3829del (p.Ile1277fs)	CEP152	Pathogenic	criteria provided, single submitter
2844652	NM_001194998.2(CEP152):c.3925C>T (p.Arg1309Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2857443	NM_001194998.2(CEP152):c.527G>A (p.Trp176Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3021593	NM_001194998.2(CEP152):c.1613C>G (p.Ser538Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
434736	NM_001194998.2(CEP152):c.3212del (p.Leu1071fs)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
503918	NM_001194998.2(CEP152):c.3249del (p.Val1084fs)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
517617	NM_001194998.2(CEP152):c.314G>A (p.Trp105Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
55	NM_001194998.2(CEP152):c.794A>C (p.Gln265Pro)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56	NM_001194998.2(CEP152):c.2959C>T (p.Arg987Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
931704	NM_001194998.2(CEP152):c.343C>T (p.Arg115Ter)	CEP152	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
977842	NM_001194998.2(CEP152):c.5070_5073del (p.Ile1691fs)	CEP152	Pathogenic	no assertion criteria provided
977865	NM_001194998.2(CEP152):c.2920C>T (p.Gln974Ter)	CEP152	Pathogenic	no assertion criteria provided
1324053	NM_001194998.2(CEP152):c.972+2T>A	CEP152	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2505978	NM_001194998.2(CEP152):c.1908+1G>T	CEP152	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3027462	NM_001194998.2(CEP152):c.419del (p.Gln140fs)	CEP152	Likely pathogenic	criteria provided, single submitter
3065928	NM_001194998.2(CEP152):c.2002C>T (p.Gln668Ter)	CEP152	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · 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
CEP152	Strong	Autosomal recessive	microcephaly 9, primary, autosomal recessive	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEP152	Orphanet:2512	Autosomal recessive primary microcephaly
CEP152	Orphanet:808	Seckel syndrome

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
CEP152	HGNC:29298	ENSG00000103995	O94986	Centrosomal protein of 152 kDa	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEP152	Centrosomal protein of 152 kDa	Necessary for centrosome duplication; the function also seems to involve CEP63, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CEP152	Other/Unknown	no		CEP152/SHC-Transforming, CEP152_CC, CEP152_PLK4_bind

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
secondary oocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEP152	218	ubiquitous	marker	secondary oocyte, oocyte, sperm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP152	1,205

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CEP152	O94986	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

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

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Centrosome maturation	1	253.8×	0.013	CEP152
Loss of Nlp from mitotic centrosomes	1	158.6×	0.013	CEP152
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.013	CEP152
AURKA Activation by TPX2	1	152.3×	0.013	CEP152
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.013	CEP152
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.013	CEP152
Mitotic G2-G2/M phases	1	126.9×	0.013	CEP152
G2/M Transition	1	126.9×	0.013	CEP152
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.013	CEP152
Anchoring of the basal body to the plasma membrane	1	113.1×	0.013	CEP152
Cilium Assembly	1	108.8×	0.013	CEP152
Mitotic Prometaphase	1	69.2×	0.017	CEP152
Organelle biogenesis and maintenance	1	66.0×	0.017	CEP152
M Phase	1	66.0×	0.017	CEP152
Cell Cycle, Mitotic	1	48.2×	0.022	CEP152
Cell Cycle	1	36.0×	0.028	CEP152

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
de novo centriole assembly involved in multi-ciliated epithelial cell differentiation	1	3370.4×	0.001	CEP152
centrosome duplication	1	936.2×	0.002	CEP152
centriole replication	1	732.7×	0.002	CEP152
cell projection organization	1	374.5×	0.003	CEP152

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
CEP152	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	CEP152

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)
CEP152	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.