Microcephaly 13, primary, autosomal recessive

Summary

Microcephaly 13, primary, autosomal recessive (MONDO:0014473) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 13, primary, autosomal recessive
Mondo ID	MONDO:0014473
OMIM	616051
DOID	DOID:0070283
UMLS	C4015080
MedGen	863517
GARD	0016054
Is cancer (heuristic)	no

Also known as: autosomal recessive primary microcephaly caused by mutation in CENPE · CENPE autosomal recessive primary microcephaly · MCPH13 · microcephaly 13, primary, autosomal recessive

Data availability: 23 ClinVar variants · 3 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 13, 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, microcephaly 9, primary, autosomal recessive, microcephalic primordial dwarfism due to ZNF335 deficiency, microcephaly 11, 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

23 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 4 benign, 3 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3899392	NM_001813.3(CENPE):c.2906C>T (p.Ala969Val)	CENPE	Pathogenic	criteria provided, single submitter
3065153	NM_001813.3(CENPE):c.1403_1404del (p.Glu468fs)	CENPE	Likely pathogenic	criteria provided, single submitter
3065382	NM_001813.3(CENPE):c.885del (p.Leu296fs)	CENPE	Likely pathogenic	criteria provided, single submitter
932106	NM_001813.3(CENPE):c.2132-1G>C	CENPE	Likely pathogenic	criteria provided, single submitter
157497	NM_001813.3(CENPE):c.2797G>A (p.Asp933Asn)	CENPE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030480	NM_001813.3(CENPE):c.1722+5G>A	CENPE	Uncertain significance	criteria provided, single submitter
1030481	NM_001813.3(CENPE):c.5035G>A (p.Glu1679Lys)	CENPE	Uncertain significance	criteria provided, multiple submitters, no conflicts
1032006	NM_001813.3(CENPE):c.7187G>A (p.Ser2396Asn)	CENPE	Uncertain significance	criteria provided, multiple submitters, no conflicts
157498	NM_001813.3(CENPE):c.4063A>G (p.Lys1355Glu)	CENPE	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679844	NM_001813.3(CENPE):c.80C>T (p.Ala27Val)	CENPE	Uncertain significance	criteria provided, single submitter
1805810	NM_001813.3(CENPE):c.6817G>A (p.Glu2273Lys)	CENPE	Uncertain significance	criteria provided, single submitter
2302121	NM_001813.3(CENPE):c.5698A>G (p.Thr1900Ala)	CENPE	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439895	NM_001813.3(CENPE):c.3494A>G (p.Asn1165Ser)	CENPE	Uncertain significance	criteria provided, multiple submitters, no conflicts
2499543	NM_001813.3(CENPE):c.2748dup (p.Leu917fs)	CENPE	Uncertain significance	criteria provided, single submitter
3265871	NM_001813.3(CENPE):c.4199C>G (p.Thr1400Ser)	CENPE	Uncertain significance	criteria provided, multiple submitters, no conflicts
3764498	NM_001813.3(CENPE):c.4333G>A (p.Asp1445Asn)	CENPE	Uncertain significance	criteria provided, single submitter
3893042	NM_001813.3(CENPE):c.6303+5G>A	CENPE	Uncertain significance	criteria provided, single submitter
4278194	NM_001813.3(CENPE):c.2186T>C (p.Leu729Pro)	CENPE	Uncertain significance	criteria provided, single submitter
434697	NM_001813.3(CENPE):c.304C>T (p.His102Tyr)	CENPE	Uncertain significance	criteria provided, multiple submitters, no conflicts
1209804	NM_001813.3(CENPE):c.5502G>A (p.Thr1834=)	CENPE	Benign	criteria provided, multiple submitters, no conflicts
1209805	NM_001813.3(CENPE):c.2025G>A (p.Gln675=)	CENPE	Benign	criteria provided, multiple submitters, no conflicts
1209806	NM_001813.3(CENPE):c.243T>C (p.Thr81=)	CENPE	Benign	criteria provided, multiple submitters, no conflicts
1209847	NM_001813.3(CENPE):c.6269C>T (p.Thr2090Met)	CENPE	Benign	criteria provided, multiple submitters, no conflicts

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
CENPE	Limited	Autosomal recessive	microcephaly 13, primary, autosomal recessive	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CENPE	Orphanet:2512	Autosomal recessive primary microcephaly
CENPE	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
CENPE	HGNC:1856	ENSG00000138778	Q02224	Centromere-associated protein E	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CENPE	Centromere-associated protein E	Microtubule plus-end-directed kinetochore motor which plays an important role in chromosome congression, microtubule-kinetochore conjugation and spindle assembly checkpoint activation.

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)
CENPE	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase

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
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CENPE	176	ubiquitous	marker	oocyte, ventricular zone, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CENPE	2,366

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CENPE	Q02224	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. 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
Amplification of signal from the kinetochores	1	196.9×	0.024	CENPE
Kinesins	1	178.4×	0.024	CENPE
Mitotic Spindle Checkpoint	1	158.6×	0.024	CENPE
Golgi-to-ER retrograde transport	1	132.8×	0.024	CENPE
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	116.5×	0.024	CENPE
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.024	CENPE
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.024	CENPE
Mitotic Metaphase and Anaphase	1	96.8×	0.024	CENPE
Mitotic Anaphase	1	96.8×	0.024	CENPE
EML4 and NUDC in mitotic spindle formation	1	92.8×	0.024	CENPE
MHC class II antigen presentation	1	89.2×	0.024	CENPE
Cell Cycle Checkpoints	1	88.5×	0.024	CENPE
Resolution of Sister Chromatid Cohesion	1	86.5×	0.024	CENPE
RHO GTPases Activate Formins	1	77.7×	0.024	CENPE
Mitotic Prometaphase	1	69.2×	0.024	CENPE
RHO GTPase Effectors	1	68.0×	0.024	CENPE
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.024	CENPE
M Phase	1	66.0×	0.024	CENPE
Separation of Sister Chromatids	1	60.7×	0.025	CENPE
Cell Cycle, Mitotic	1	48.2×	0.030	CENPE
Membrane Trafficking	1	37.1×	0.033	CENPE
Hemostasis	1	36.0×	0.033	CENPE
Cell Cycle	1	36.0×	0.033	CENPE
Vesicle-mediated transport	1	34.8×	0.033	CENPE
Signaling by Rho GTPases	1	34.2×	0.033	CENPE
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.033	CENPE
Adaptive Immune System	1	29.8×	0.036	CENPE
Immune System	1	13.0×	0.080	CENPE
Signal Transduction	1	10.2×	0.098	CENPE

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
microtubule plus-end directed mitotic chromosome migration	1	16852.0×	4e-04	CENPE
lateral attachment of mitotic spindle microtubules to kinetochore	1	16852.0×	4e-04	CENPE
mitotic chromosome movement towards spindle pole	1	3370.4×	0.001	CENPE
kinetochore assembly	1	1203.7×	0.002	CENPE
metaphase chromosome alignment	1	1053.2×	0.002	CENPE
attachment of mitotic spindle microtubules to kinetochore	1	1053.2×	0.002	CENPE
positive regulation of protein kinase activity	1	674.1×	0.003	CENPE
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.004	CENPE
mitotic metaphase chromosome alignment	1	383.0×	0.004	CENPE
microtubule-based movement	1	295.6×	0.005	CENPE
mitotic spindle organization	1	271.8×	0.005	CENPE
chromosome segregation	1	173.7×	0.007	CENPE
mitotic cell cycle	1	133.8×	0.008	CENPE
cell division	1	46.2×	0.022	CENPE

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CENPE	1	1

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GSK-923295A	1	CENPE

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CENPE	346	Functional:241, Binding:105

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CENPE	346

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
GSK-923295A	1	CENPE

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	1	CENPE
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.