Microcephaly 12, primary, autosomal recessive

Summary

Microcephaly 12, primary, autosomal recessive (MONDO:0014484) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 12, primary, autosomal recessive
Mondo ID	MONDO:0014484
OMIM	616080
DOID	DOID:0070284
UMLS	C4015156
MedGen	863593
GARD	0016057
Is cancer (heuristic)	no

Also known as: autosomal recessive primary microcephaly caused by mutation in CDK6 · CDK6 autosomal recessive primary microcephaly · MCPH12 · microcephaly 12, primary, autosomal recessive

Data availability: 1 ClinVar variant · 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 12, 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 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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
157508	NM_001145306.2(CDK6):c.589G>A (p.Ala197Thr)	CDK6	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
CDK6	Supportive	Autosomal recessive	autosomal recessive primary microcephaly	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDK6	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
CDK6	HGNC:1777	ENSG00000105810	Q00534	Cyclin-dependent kinase 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDK6	Cyclin-dependent kinase 6	Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition.

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)
CDK6	Kinase	yes	2.7.11.22	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
adrenal tissue	1
pylorus	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDK6	262	ubiquitous	marker	adrenal tissue, trabecular bone tissue, pylorus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDK6	6,767

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDK6	Q00534	22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 28. 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
Diseases of Cellular Senescence	1	3806.7×	0.001	CDK6
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	1	3806.7×	0.001	CDK6
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	3806.7×	0.001	CDK6
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	1	3806.7×	0.001	CDK6
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	3806.7×	0.001	CDK6
Diseases of cellular response to stress	1	3806.7×	0.001	CDK6
Drug-mediated inhibition of CDK4/CDK6 activity	1	2284.0×	0.002	CDK6
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1	878.5×	0.004	CDK6
Regulation of RUNX1 Expression and Activity	1	671.8×	0.004	CDK6
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	1	634.4×	0.004	CDK6
Aberrant regulation of mitotic cell cycle due to RB1 defects	1	407.9×	0.005	CDK6
G1 Phase	1	393.8×	0.005	CDK6
Diseases of mitotic cell cycle	1	393.8×	0.005	CDK6
Oncogene Induced Senescence	1	335.9×	0.006	CDK6
Cyclin D associated events in G1	1	233.1×	0.008	CDK6
Mitotic G1 phase and G1/S transition	1	184.2×	0.010	CDK6
Transcriptional regulation by RUNX1	1	146.4×	0.011	CDK6
Cellular Senescence	1	137.6×	0.011	CDK6
Senescence-Associated Secretory Phenotype (SASP)	1	99.3×	0.015	CDK6
Oxidative Stress Induced Senescence	1	90.6×	0.015	CDK6
Cell Cycle, Mitotic	1	48.2×	0.028	CDK6
Cellular responses to stress	1	36.8×	0.034	CDK6
Cell Cycle	1	36.0×	0.034	CDK6
Cellular responses to stimuli	1	31.5×	0.037	CDK6
RNA Polymerase II Transcription	1	22.5×	0.050	CDK6
Gene expression (Transcription)	1	17.8×	0.060	CDK6
Generic Transcription Pathway	1	15.1×	0.069	CDK6
Disease	1	13.1×	0.076	CDK6

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
gliogenesis	1	2808.7×	0.003	CDK6
cell dedifferentiation	1	2808.7×	0.003	CDK6
regulation of erythrocyte differentiation	1	2808.7×	0.003	CDK6
negative regulation of monocyte differentiation	1	2407.4×	0.003	CDK6
generation of neurons	1	1532.0×	0.003	CDK6
regulation of hematopoietic stem cell differentiation	1	1532.0×	0.003	CDK6
type B pancreatic cell development	1	1296.3×	0.003	CDK6
regulation of G2/M transition of mitotic cell cycle	1	1296.3×	0.003	CDK6
lateral ventricle development	1	1296.3×	0.003	CDK6
astrocyte development	1	1123.5×	0.003	CDK6
regulation of cell motility	1	991.3×	0.003	CDK6
negative regulation of myeloid cell differentiation	1	936.2×	0.003	CDK6
hematopoietic stem cell differentiation	1	766.0×	0.003	CDK6
positive regulation of cell-matrix adhesion	1	674.1×	0.003	CDK6
negative regulation of cellular senescence	1	648.1×	0.003	CDK6
dentate gyrus development	1	624.1×	0.003	CDK6
T cell differentiation in thymus	1	411.0×	0.005	CDK6
negative regulation of osteoblast differentiation	1	295.6×	0.005	CDK6
positive regulation of fibroblast proliferation	1	295.6×	0.005	CDK6
negative regulation of cell cycle	1	290.6×	0.005	CDK6
negative regulation of epithelial cell proliferation	1	290.6×	0.005	CDK6
negative regulation of cell differentiation	1	285.6×	0.005	CDK6
G1/S transition of mitotic cell cycle	1	200.6×	0.007	CDK6
response to virus	1	144.0×	0.009	CDK6
Notch signaling pathway	1	141.6×	0.009	CDK6
regulation of gene expression	1	83.4×	0.015	CDK6
regulation of cell cycle	1	74.6×	0.016	CDK6
DNA damage response	1	53.5×	0.022	CDK6
cell division	1	46.2×	0.025	CDK6
negative regulation of cell population proliferation	1	42.1×	0.026	CDK6

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
CDK6	PALBOCICLIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDK6	45	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PALBOCICLIB	4	CDK6
ABEMACICLIB	4	CDK6
RIBOCICLIB	4	CDK6
TRILACICLIB	4	CDK6
MOMELOTINIB	4	CDK6
SORAFENIB	4	CDK6
DABRAFENIB	4	CDK6
OLAPARIB	4	CDK6
LEROCICLIB	3	CDK6
ALVOCIDIB	3	CDK6
DINACICLIB	3	CDK6
DALPICICLIB	3	CDK6
QUERCETIN	3	CDK6
DOVITINIB	3	CDK6
LESTAURTINIB	3	CDK6
RIVICICLIB	2	CDK6
ULECACICLIB	2	CDK6
CROZBACICLIB	2	CDK6
EBVACICLIB	2	CDK6
AT-7519	2	CDK6
ATIRMOCICLIB	2	CDK6
SELICICLIB	2	CDK6
NARAZACICLIB	2	CDK6
ECIRUCICLIB	2	CDK6
CULMERCICLIB	2	CDK6
ISTISOCICLIB	2	CDK6
TEGTOCICLIB	2	CDK6
ZOTIRACICLIB	2	CDK6
FISETIN	2	CDK6
RG-547	2	CDK6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CDK6	715	Binding:691, Functional:24

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CDK6	2.7.11.22	cyclin-dependent kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CDK6	715

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

30 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)
PALBOCICLIB	4	CDK6
ABEMACICLIB	4	CDK6
RIBOCICLIB	4	CDK6
TRILACICLIB	4	CDK6
MOMELOTINIB	4	CDK6
SORAFENIB	4	CDK6
DABRAFENIB	4	CDK6
OLAPARIB	4	CDK6
LEROCICLIB	3	CDK6
ALVOCIDIB	3	CDK6
DINACICLIB	3	CDK6
DALPICICLIB	3	CDK6
QUERCETIN	3	CDK6
DOVITINIB	3	CDK6
LESTAURTINIB	3	CDK6
RIVICICLIB	2	CDK6
ULECACICLIB	2	CDK6
CROZBACICLIB	2	CDK6
EBVACICLIB	2	CDK6
AT-7519	2	CDK6
ATIRMOCICLIB	2	CDK6
SELICICLIB	2	CDK6
NARAZACICLIB	2	CDK6
ECIRUCICLIB	2	CDK6
CULMERCICLIB	2	CDK6
ISTISOCICLIB	2	CDK6
TEGTOCICLIB	2	CDK6
ZOTIRACICLIB	2	CDK6
FISETIN	2	CDK6
RG-547	2	CDK6

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CDK6
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.