Microcephaly with intellectual disability

Summary

Microcephaly with intellectual disability (MONDO:0100200) is a disease caused by MCPH1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MCPH1 (GenCC Strong)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly with intellectual disability
Mondo ID	MONDO:0100200
GARD	0026081
Is cancer (heuristic)	no

Also known as: microcephaly with neurodevelopmental phenotypes

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › microcephaly › microcephaly with intellectual disability

Related subtypes (9): microcephalic osteodysplastic primordial dwarfism, microcephaly and chorioretinopathy, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Amish lethal microcephaly, microcephaly, seizures, and developmental delay, isolated congenital microcephaly, isolated microcephaly, microcephaly with lissencephaly and/or hydranencephaly, microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia

Subtypes (1): microcephaly 1, 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
MCPH1	Definitive	Autosomal recessive	microcephaly 1, primary, autosomal recessive	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MCPH1	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
MCPH1	HGNC:6954	ENSG00000147316	Q8NEM0	Microcephalin	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MCPH1	Microcephalin	Implicated in chromosome condensation and DNA damage induced cellular responses.

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)
MCPH1	Other/Unknown	no		BRCT_dom, Microcephalin-like, Microcephalin_mammal

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
calcaneal tendon	1
ganglionic eminence	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MCPH1	204	ubiquitous	marker	secondary oocyte, ganglionic eminence, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MCPH1	1,499

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MCPH1	Q8NEM0	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Mitotic Prophase	1	368.4×	0.014	MCPH1
Condensation of Prophase Chromosomes	1	156.4×	0.016	MCPH1
M Phase	1	66.0×	0.025	MCPH1
Cell Cycle, Mitotic	1	48.2×	0.026	MCPH1
Cell Cycle	1	36.0×	0.028	MCPH1

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 chromosome condensation	1	8426.0×	0.001	MCPH1
regulation of centrosome cycle	1	1872.4×	0.003	MCPH1
protein localization to centrosome	1	674.1×	0.004	MCPH1
neuronal stem cell population maintenance	1	674.1×	0.004	MCPH1
establishment of mitotic spindle orientation	1	481.5×	0.004	MCPH1
bone development	1	276.3×	0.006	MCPH1
cerebral cortex development	1	205.5×	0.007	MCPH1
regulation of inflammatory response	1	168.5×	0.007	MCPH1
mitotic cell cycle	1	133.8×	0.008	MCPH1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	MCPH1

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
MCPH1	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	MCPH1

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)
MCPH1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.