Microcephaly 30, primary, autosomal recessive

Summary

Microcephaly 30, primary, autosomal recessive (MONDO:0859342) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 30, primary, autosomal recessive
Mondo ID	MONDO:0859342
OMIM	620183
DOID	DOID:0051041
UMLS	C5774280
MedGen	1824053
GARD	0026708
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants · 4 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 30, 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 22, primary, autosomal recessive, microcephaly 23, primary, autosomal recessive, microcephaly with or without short stature, 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

5 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1806482	NM_004336.5(BUB1):c.2625+1G>A	BUB1	Pathogenic	no assertion criteria provided
1806483	NM_004336.5(BUB1):c.2197dup (p.Ala733fs)	BUB1	Pathogenic	no assertion criteria provided
3377649	NM_004336.5(BUB1):c.1430dup (p.Pro478fs)	BUB1	Likely pathogenic	criteria provided, single submitter
1806481	NM_004336.5(BUB1):c.2T>G (p.Met1Arg)	BUB1	Uncertain significance	criteria provided, single submitter
3377648	NM_004336.5(BUB1):c.307A>T (p.Ile103Phe)	BUB1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
BUB1	Moderate	Autosomal recessive	microcephaly 30, primary, autosomal recessive	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BUB1	Orphanet:1052	Mosaic variegated aneuploidy 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
BUB1	HGNC:1148	ENSG00000169679	O43683	Mitotic checkpoint serine/threonine-protein kinase BUB1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BUB1	Mitotic checkpoint serine/threonine-protein kinase BUB1	Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BUB1	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-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
ganglionic eminence	1
primordial germ cell in gonad	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BUB1	185	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BUB1	3,618

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BUB1	O43683	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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×	0.023	BUB1
Mitotic Spindle Checkpoint	1	158.6×	0.023	BUB1
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	116.5×	0.023	BUB1
Mitotic Metaphase and Anaphase	1	96.8×	0.023	BUB1
Mitotic Anaphase	1	96.8×	0.023	BUB1
EML4 and NUDC in mitotic spindle formation	1	92.8×	0.023	BUB1
Cell Cycle Checkpoints	1	88.5×	0.023	BUB1
Resolution of Sister Chromatid Cohesion	1	86.5×	0.023	BUB1
RHO GTPases Activate Formins	1	77.7×	0.023	BUB1
Mitotic Prometaphase	1	69.2×	0.023	BUB1
RHO GTPase Effectors	1	68.0×	0.023	BUB1
M Phase	1	66.0×	0.023	BUB1
Separation of Sister Chromatids	1	60.7×	0.023	BUB1
Cell Cycle, Mitotic	1	48.2×	0.027	BUB1
Cell Cycle	1	36.0×	0.032	BUB1
Signaling by Rho GTPases	1	34.2×	0.032	BUB1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.032	BUB1
Signal Transduction	1	10.2×	0.098	BUB1

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 sister chromatid cohesion	1	16852.0×	2e-04	BUB1
positive regulation of maintenance of mitotic sister chromatid cohesion, centromeric	1	16852.0×	2e-04	BUB1
meiotic sister chromatid cohesion, centromeric	1	3370.4×	8e-04	BUB1
regulation of chromosome segregation	1	1872.4×	0.001	BUB1
mitotic spindle assembly checkpoint signaling	1	561.7×	0.003	BUB1
chromosome segregation	1	173.7×	0.008	BUB1
cell division	1	46.2×	0.025	BUB1
apoptotic process	1	28.7×	0.035	BUB1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BUB1	GILTERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BUB1	10	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GILTERITINIB	4	BUB1
SUNITINIB	4	BUB1
ERLOTINIB	4	BUB1
LOSMAPIMOD	3	BUB1
ICOTINIB	3	BUB1
AT-9283	2	BUB1
MILCICLIB	2	BUB1
XL-019	1	BUB1
CYC-116	1	BUB1
CUDC-101	1	BUB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
BUB1	86	Binding:84, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BUB1	2.7.11.1	non-specific serine/threonine protein kinase

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

10 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)
GILTERITINIB	4	BUB1
SUNITINIB	4	BUB1
ERLOTINIB	4	BUB1
LOSMAPIMOD	3	BUB1
ICOTINIB	3	BUB1
AT-9283	2	BUB1
MILCICLIB	2	BUB1
XL-019	1	BUB1
CYC-116	1	BUB1
CUDC-101	1	BUB1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BUB1
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	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.