Microcephaly 22, primary, autosomal recessive

Summary

Microcephaly 22, primary, autosomal recessive (MONDO:0054805) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 22, primary, autosomal recessive
Mondo ID	MONDO:0054805
OMIM	617984
DOID	DOID:0051033
UMLS	C4693834
MedGen	1635688
GARD	0016279
Is cancer (heuristic)	no

Also known as: MCPH22

Data availability: 22 ClinVar variants · 2 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 22, 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 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 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

22 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 5 pathogenic, 5 benign, 3 likely pathogenic, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1032666	NM_015261.3(NCAPD3):c.3278_3281del (p.Lys1093fs)	NCAPD3	Pathogenic	criteria provided, single submitter
4278373	NM_015261.3(NCAPD3):c.2675-1G>A	NCAPD3	Pathogenic	criteria provided, single submitter
524197	NM_015261.3(NCAPD3):c.1783del (p.Val595fs)	NCAPD3	Pathogenic	no assertion criteria provided
524198	NM_015261.3(NCAPD3):c.382+14A>G	NCAPD3	Pathogenic	no assertion criteria provided
524199	NM_015261.3(NCAPD3):c.3458A>C (p.Glu1153Ala)	NCAPD3	Pathogenic	no assertion criteria provided
3064698	NM_015261.3(NCAPD3):c.4388+1G>A	NCAPD3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3065840	NM_015261.3(NCAPD3):c.3229C>T (p.Gln1077Ter)	NCAPD3	Likely pathogenic	criteria provided, single submitter
4849486	NM_015261.3(NCAPD3):c.1273del (p.Arg425fs)	NCAPD3	Likely pathogenic	criteria provided, single submitter
1029374	NM_015261.3(NCAPD3):c.2135C>T (p.Thr712Met)	NCAPD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029375	NM_015261.3(NCAPD3):c.2257A>G (p.Asn753Asp)	NCAPD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029372	NM_015261.3(NCAPD3):c.1000G>A (p.Ala334Thr)	NCAPD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1029376	NM_015261.3(NCAPD3):c.2707G>A (p.Ala903Thr)	NCAPD3	Uncertain significance	criteria provided, single submitter
1031889	NM_015261.3(NCAPD3):c.2062G>T (p.Ala688Ser)	NCAPD3	Uncertain significance	criteria provided, single submitter
2434068	NM_015261.3(NCAPD3):c.2816A>G (p.Lys939Arg)	NCAPD3	Uncertain significance	criteria provided, single submitter
2434069	NM_015261.3(NCAPD3):c.3197_3198del (p.Asn1065_Tyr1066insTer)	NCAPD3	Uncertain significance	criteria provided, single submitter
3362842	NM_015261.3(NCAPD3):c.4028A>C (p.Lys1343Thr)	NCAPD3	Uncertain significance	criteria provided, single submitter
4079364	NM_015261.3(NCAPD3):c.3572_3573+2del	NCAPD3	Uncertain significance	criteria provided, single submitter
1321850	NM_015261.3(NCAPD3):c.2892A>G (p.Val964=)	NCAPD3	Benign	criteria provided, multiple submitters, no conflicts
1321851	NM_015261.3(NCAPD3):c.1689+20A>G	NCAPD3	Benign	criteria provided, multiple submitters, no conflicts
1321852	NM_015261.3(NCAPD3):c.1525+18T>A	NCAPD3	Benign	criteria provided, multiple submitters, no conflicts
1321853	NM_015261.3(NCAPD3):c.1215+28G>A	NCAPD3	Benign	criteria provided, multiple submitters, no conflicts
1321854	NM_015261.3(NCAPD3):c.1090-33A>G	NCAPD3	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
NCAPD3	Moderate	Autosomal recessive	microcephaly 22, primary, autosomal recessive	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NCAPD3	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
NCAPD3	HGNC:28952	ENSG00000151503	P42695	Condensin-2 complex subunit D3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NCAPD3	Condensin-2 complex subunit D3	Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis.

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)
NCAPD3	Other/Unknown	no		ARM-like, NCAPD3, ARM-type_fold

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
secondary oocyte	1
sural nerve	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NCAPD3	226	ubiquitous	marker	sural nerve, secondary oocyte, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NCAPD3	2,202

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NCAPD3	P42695	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Condensation of Prophase Chromosomes	1	156.4×	0.006	NCAPD3

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
meiotic chromosome condensation	1	2808.7×	0.001	NCAPD3
positive regulation of chromosome condensation	1	2106.5×	0.001	NCAPD3
positive regulation of chromosome separation	1	1685.2×	0.001	NCAPD3
positive regulation of chromosome segregation	1	1296.3×	0.001	NCAPD3
mitotic chromosome condensation	1	991.3×	0.001	NCAPD3
cell division	1	46.2×	0.022	NCAPD3

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
NCAPD3	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	NCAPD3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
NCAPD3	6	Binding:6

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)
MOLIBRESIB	2	NCAPD3

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	NCAPD3
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.