Autosomal recessive primary microcephaly

Summary

Autosomal recessive primary microcephaly (MONDO:0016660) is a disease (an umbrella term covering 29 Mondo subtypes) caused by variants in ASPM, KIF14, and STIL, with 27 cohort genes. The dominant Reactome pathway is Loss of Nlp from mitotic centrosomes (5 cohort genes).

At a glance

• Prevalence: 1-9 / 1 000 000 (Specific population) [Orphanet-validated]
• Causal genes: ASPM (GenCC Definitive), KIF14 (GenCC Definitive), STIL (GenCC Definitive)
• Umbrella term: 29 Mondo subtypes
• Cohort genes: 27
• ClinVar variants: 45
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.1	Specific population	Validated
Annual incidence	1-9 / 100 000	1	Pakistan	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0000219	Thin upper lip vermilion	Very frequent (80-99%)
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0000340	Sloping forehead	Very frequent (80-99%)
HP:0000582	Upslanted palpebral fissure	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001510	Growth delay	Very frequent (80-99%)
HP:0002282	Gray matter heterotopia	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0010864	Intellectual disability, severe	Very frequent (80-99%)
HP:0000076	Vesicoureteral reflux	Frequent (30-79%)
HP:0000122	Unilateral renal agenesis	Frequent (30-79%)
HP:0001274	Agenesis of corpus callosum	Frequent (30-79%)
HP:0001302	Pachygyria	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0002119	Ventriculomegaly	Frequent (30-79%)
HP:0003103	Abnormal cortical bone morphology	Frequent (30-79%)
HP:0007333	Hypoplasia of the frontal lobes	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive primary microcephaly
Mondo ID	MONDO:0016660
MeSH	C579935
OMIM	251200
Orphanet	2512
DOID	DOID:0070296
SNOMED CT	715981004
UMLS	C3711387
MedGen	777995
GARD	0012117
Is cancer (heuristic)	no

Also known as: MCPH · microcephalia vera · microcephaly vera · microcephaly, primary autosomal recessive · microcephaly, primary, autosomal recessive · true microcephaly

Data availability: 45 ClinVar variants · 27 GenCC gene-disease records.

Disease family

An umbrella term covering 29 Mondo subtypes.

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

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

Subtypes (29): 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 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

45 retrieved; paginated sample, class counts are floors:

25 pathogenic, 9 likely pathogenic, 5 pathogenic/likely pathogenic, 3 uncertain significance, 3 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
4688532	NC_000008.10:g.(6264211_6266799)_(6357451_6478974)del	ANGPT2	Pathogenic	criteria provided, single submitter
4688536	NC_000008.10:g.(?6264147)(6357451_6478974)del	ANGPT2	Pathogenic	criteria provided, single submitter
157795	NM_018136.5(ASPM):c.2419+2T>C	ASPM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
157867	NM_018136.5(ASPM):c.7160_7161del (p.Ser2387fs)	ASPM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21582	NM_018136.5(ASPM):c.3796G>T (p.Glu1266Ter)	ASPM	Pathogenic	criteria provided, multiple submitters, no conflicts
2581671	NM_018136.5(ASPM):c.8195_8196del (p.Arg2732fs)	ASPM	Pathogenic	criteria provided, single submitter
3384969	NM_018136.5(ASPM):c.6107_6110del (p.Val2036fs)	ASPM	Pathogenic	criteria provided, single submitter
3600659	NM_018136.5(ASPM):c.5505del (p.Phe1835fs)	ASPM	Pathogenic	criteria provided, multiple submitters, no conflicts
3902244	NM_018136.5(ASPM):c.3483_3484del (p.Ile1161fs)	ASPM	Pathogenic	criteria provided, single submitter
3902257	NM_018136.5(ASPM):c.1480del (p.Ser494fs)	ASPM	Pathogenic	criteria provided, single submitter
432552	NM_018136.5(ASPM):c.1697C>A (p.Ser566Ter)	ASPM	Pathogenic	criteria provided, multiple submitters, no conflicts
4687500	NM_018136.5(ASPM):c.4598_4601del (p.Asn1533fs)	ASPM	Pathogenic	criteria provided, single submitter
4960	NM_018136.5(ASPM):c.9178C>T (p.Gln3060Ter)	ASPM	Pathogenic	criteria provided, multiple submitters, no conflicts
631585	NM_018136.5(ASPM):c.4849C>T (p.Arg1617Ter)	ASPM	Pathogenic	criteria provided, multiple submitters, no conflicts
252992	NM_001206999.2(CIT):c.1111+1G>A	CIT	Pathogenic	criteria provided, single submitter
252993	NM_001206999.2(CIT):c.412C>T (p.Gln138Ter)	CIT	Pathogenic	no assertion criteria provided
252994	NM_001206999.2(CIT):c.473C>G (p.Pro158Arg)	CIT	Pathogenic	no assertion criteria provided
210670	NM_018451.5(CPAP):c.898_899del (p.Glu300fs)	CPAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
158830	NM_024596.5(MCPH1):c.1869_1870del (p.Ser623_Cys624insTer)	MCPH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2691298	NM_024596.5(MCPH1):c.698C>A (p.Ser233Ter)	MCPH1	Pathogenic	criteria provided, multiple submitters, no conflicts
2826934	NM_024596.5(MCPH1):c.595C>T (p.Gln199Ter)	MCPH1	Pathogenic	criteria provided, multiple submitters, no conflicts
30641	NM_024596.5(MCPH1):c.215C>T (p.Ser72Leu)	MCPH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3902579	NM_024596.5(MCPH1):c.2312del (p.Pro771fs)	MCPH1	Pathogenic	criteria provided, single submitter
4847425	NM_024596.5(MCPH1):c.2021C>G (p.Ser674Ter)	MCPH1	Pathogenic	criteria provided, single submitter
4847982	NC_000008.10:g.(?6264147)(6293684_6296473)del	MCPH1	Pathogenic	criteria provided, single submitter
4848157	NM_024596.5(MCPH1):c.1341_1344del (p.Ser448fs)	MCPH1	Pathogenic	criteria provided, single submitter
2581189	NM_024596.5(MCPH1):c.2404G>T (p.Gly802Ter)	MCPH1-AS1	Pathogenic	criteria provided, single submitter
31037	NM_001083961.2(WDR62):c.1531G>A (p.Asp511Asn)	WDR62	Pathogenic	criteria provided, multiple submitters, no conflicts
3336245	NC_000019.9:g.(36564434_36572334)_(36575647_36577588)del	WDR62	Pathogenic	criteria provided, single submitter
3896394	NC_000019.9:g.(36550933_36556859)_(36564434_36572334)del	WDR62	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 108 · Orphanet: 35 · 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
ASPM	Definitive	Autosomal recessive	autosomal recessive primary microcephaly	5
CPAP	Definitive	Autosomal recessive	microcephaly 6 with or without short stature	5
KIF14	Definitive	Autosomal recessive	autosomal recessive primary microcephaly	7
MCPH1	Definitive	Autosomal recessive	microcephaly 1, primary, autosomal recessive	6
MFSD2A	Definitive	Autosomal recessive	microcephaly 15, primary, autosomal recessive	4
STIL	Definitive	Autosomal recessive	autosomal recessive primary microcephaly	6
WDR62	Definitive	Autosomal recessive	microcephaly 2, primary, autosomal recessive, with or without cortical malformations	8
ANKLE2	Strong	Autosomal recessive	microcephaly 16, primary, autosomal recessive	4
CDK5RAP2	Strong	Autosomal recessive	microcephaly 3, primary, autosomal recessive	5
CEP135	Strong	Autosomal recessive	microcephaly 8, primary, autosomal recessive	3
CEP152	Strong	Autosomal recessive	microcephaly 9, primary, autosomal recessive	4
CIT	Strong	Autosomal recessive	microcephaly 17, primary, autosomal recessive	4
KNL1	Strong	Autosomal recessive	microcephaly 4, primary, autosomal recessive	4
SASS6	Strong	Autosomal recessive	microcephaly 14, primary, autosomal recessive	5
NCAPD3	Moderate	Autosomal recessive	microcephaly 22, primary, autosomal recessive	3
PHC1	Moderate	Autosomal recessive	microcephaly 11, primary, autosomal recessive	4
CDK6	Supportive	Autosomal recessive	autosomal recessive primary microcephaly	2
CEP63	Supportive	Autosomal recessive	autosomal recessive primary microcephaly	4
COPB2	Supportive	Autosomal recessive	autosomal recessive primary microcephaly	7
METTL5	Supportive	Autosomal recessive	autosomal recessive primary microcephaly	5
PYCR2	Supportive	Autosomal recessive	autosomal recessive primary microcephaly	5
TAF13	Supportive	Autosomal recessive	autosomal recessive primary microcephaly	5
TRAPPC14	Supportive	Autosomal recessive	autosomal recessive primary microcephaly
TEDC1	Limited	Autosomal recessive	microcephaly	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TAF13	Orphanet:2512	Autosomal recessive primary microcephaly
CPAP	Orphanet:2512	Autosomal recessive primary microcephaly
CPAP	Orphanet:808	Seckel syndrome
ASPM	Orphanet:2512	Autosomal recessive primary microcephaly
CIT	Orphanet:2512	Autosomal recessive primary microcephaly
WDR62	Orphanet:2512	Autosomal recessive primary microcephaly
MCPH1	Orphanet:2512	Autosomal recessive primary microcephaly
STIL	Orphanet:220386	Semilobar holoprosencephaly
STIL	Orphanet:2512	Autosomal recessive primary microcephaly
STIL	Orphanet:280195	Septopreoptic holoprosencephaly
STIL	Orphanet:93924	Lobar holoprosencephaly
STIL	Orphanet:93925	Alobar holoprosencephaly
STIL	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
STIL	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
CDK6	Orphanet:2512	Autosomal recessive primary microcephaly
CDK5RAP2	Orphanet:2512	Autosomal recessive primary microcephaly
KIF14	Orphanet:2512	Autosomal recessive primary microcephaly
KIF14	Orphanet:439897	Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome
COPB2	Orphanet:2512	Autosomal recessive primary microcephaly
KNL1	Orphanet:2512	Autosomal recessive primary microcephaly
METTL5	Orphanet:2512	Autosomal recessive primary microcephaly
SASS6	Orphanet:2512	Autosomal recessive primary microcephaly
TRAPPC14	Orphanet:2512	Autosomal recessive primary microcephaly
CEP63	Orphanet:808	Seckel syndrome
MFSD2A	Orphanet:2512	Autosomal recessive primary microcephaly
NCAPD3	Orphanet:2512	Autosomal recessive primary microcephaly
CEP135	Orphanet:2512	Autosomal recessive primary microcephaly
ANKLE2	Orphanet:2512	Autosomal recessive primary microcephaly
CEP152	Orphanet:2512	Autosomal recessive primary microcephaly
CEP152	Orphanet:808	Seckel syndrome
PYCR2	Orphanet:2512	Autosomal recessive primary microcephaly
PYCR2	Orphanet:481152	PYCR2-related microcephaly-progressive leukoencephalopathy
PHC1	Orphanet:2512	Autosomal recessive primary microcephaly
ZNF335	Orphanet:329228	Microcephalic primordial dwarfism due to ZNF335 deficiency
ANGPT2	Orphanet:363999	Non-immune hydrops fetalis

Cohort genes → proteins

27 cohort genes, 26 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	27

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TAF13	HGNC:11546	ENSG00000197780	Q15543	Transcription initiation factor TFIID subunit 13	gencc,clinvar
CPAP	HGNC:17272	ENSG00000151849	Q9HC77	Centrosomal P4.1-associated protein	gencc,clinvar
ASPM	HGNC:19048	ENSG00000066279	Q8IZT6	Abnormal spindle-like microcephaly-associated protein	gencc,clinvar
CIT	HGNC:1985	ENSG00000122966	O14578	Citron Rho-interacting kinase	gencc,clinvar
WDR62	HGNC:24502	ENSG00000075702	O43379	WD repeat-containing protein 62	gencc,clinvar
MCPH1	HGNC:6954	ENSG00000147316	Q8NEM0	Microcephalin	gencc,clinvar
STIL	HGNC:10879	ENSG00000123473	Q15468	SCL-interrupting locus protein	gencc
CDK6	HGNC:1777	ENSG00000105810	Q00534	Cyclin-dependent kinase 6	gencc
CDK5RAP2	HGNC:18672	ENSG00000136861	Q96SN8	CDK5 regulatory subunit-associated protein 2	gencc
KIF14	HGNC:19181	ENSG00000118193	Q15058	Kinesin-like protein KIF14	gencc
TEDC1	HGNC:20127	ENSG00000185347	Q86SX3	Tubulin epsilon and delta complex protein 1	gencc
COPB2	HGNC:2232	ENSG00000184432	P35606	Coatomer subunit beta'	gencc
KNL1	HGNC:24054	ENSG00000137812	Q8NG31	Outer kinetochore KNL1 complex subunit KNL1	gencc
METTL5	HGNC:25006	ENSG00000138382	Q9NRN9	rRNA N(6)-adenosine-methyltransferase METTL5	gencc
SASS6	HGNC:25403	ENSG00000156876	Q6UVJ0	Spindle assembly abnormal protein 6 homolog	gencc
TRAPPC14	HGNC:25604	ENSG00000146826	Q8WVR3	Trafficking protein particle complex subunit 14	gencc
CEP63	HGNC:25815	ENSG00000182923	Q96MT8	Centrosomal protein of 63 kDa	gencc
MFSD2A	HGNC:25897	ENSG00000168389	Q8NA29	Sodium-dependent lysophosphatidylcholine symporter 1	gencc
NCAPD3	HGNC:28952	ENSG00000151503	P42695	Condensin-2 complex subunit D3	gencc
CEP135	HGNC:29086	ENSG00000174799	Q66GS9	Centrosomal protein of 135 kDa	gencc
ANKLE2	HGNC:29101	ENSG00000176915	Q86XL3	Ankyrin repeat and LEM domain-containing protein 2	gencc
CEP152	HGNC:29298	ENSG00000103995	O94986	Centrosomal protein of 152 kDa	gencc
PYCR2	HGNC:30262	ENSG00000143811	Q96C36	Pyrroline-5-carboxylate reductase 2	gencc
PHC1	HGNC:3182	ENSG00000111752	P78364	Polyhomeotic-like protein 1	gencc
ZNF335	HGNC:15807	ENSG00000198026	Q9H4Z2	Zinc finger protein 335	clinvar
ANGPT2	HGNC:485	ENSG00000091879	O15123	Angiopoietin-2	clinvar
MCPH1-AS1	HGNC:51655	ENSG00000249898		MCPH1 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TAF13	Transcription initiation factor TFIID subunit 13	The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription.
CPAP	Centrosomal P4.1-associated protein	Plays an important role in cell division and centrosome function by participating in centriole duplication.
ASPM	Abnormal spindle-like microcephaly-associated protein	Involved in mitotic spindle regulation and coordination of mitotic processes.
CIT	Citron Rho-interacting kinase	Plays a role in cytokinesis.
WDR62	WD repeat-containing protein 62	Required for cerebral cortical development.
MCPH1	Microcephalin	Implicated in chromosome condensation and DNA damage induced cellular responses.
STIL	SCL-interrupting locus protein	Immediate-early gene.
CDK6	Cyclin-dependent kinase 6	Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition.
CDK5RAP2	CDK5 regulatory subunit-associated protein 2	Potential regulator of CDK5 activity via its interaction with CDK5R1.
KIF14	Kinesin-like protein KIF14	Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity.
TEDC1	Tubulin epsilon and delta complex protein 1	Acts as a positive regulator of ciliary hedgehog signaling.
COPB2	Coatomer subunit beta'	The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Go…
KNL1	Outer kinetochore KNL1 complex subunit KNL1	Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions.
METTL5	rRNA N(6)-adenosine-methyltransferase METTL5	Catalytic subunit of a heterodimer with TRMT112, which specifically methylates the 6th position of adenine in position 1832 of 18S rRNA.
SASS6	Spindle assembly abnormal protein 6 homolog	Central scaffolding component of the centrioles ensuring their 9-fold symmetry.
TRAPPC14	Trafficking protein particle complex subunit 14	Specific subunit of the TRAPP (transport protein particle) II complex, a highly conserved vesicle tethering complex that functions in late Golgi trafficking as a membrane tether.
CEP63	Centrosomal protein of 63 kDa	Required for normal spindle assembly.
MFSD2A	Sodium-dependent lysophosphatidylcholine symporter 1	Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function.
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.
CEP135	Centrosomal protein of 135 kDa	Centrosomal microtubule-binding protein involved in centriole biogenesis.
ANKLE2	Ankyrin repeat and LEM domain-containing protein 2	Involved in mitotic nuclear envelope reassembly by promoting dephosphorylation of BAF/BANF1 during mitotic exit.
CEP152	Centrosomal protein of 152 kDa	Necessary for centrosome duplication; the function also seems to involve CEP63, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication.
PYCR2	Pyrroline-5-carboxylate reductase 2	Oxidoreductase that catalyzes the last step in proline biosynthesis, which corresponds to the reduction of pyrroline-5-carboxylate to L-proline using NAD(P)H.
PHC1	Polyhomeotic-like protein 1	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.
ZNF335	Zinc finger protein 335	Component or associated component of some histone methyltransferase complexes may regulate transcription through recruitment of those complexes on gene promoters.
ANGPT2	Angiopoietin-2	Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling.

Protein-family classification

Druggable: 4 · Difficult: 5 · Unknown: 18 · Druggable fraction: 0.15

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
Transporter	1	2.9×	0.442
Kinase	2	2.0×	0.442
Scaffold/PPI	3	1.9×	0.442
Other/Unknown	18	1.2×	0.442
Antibody/Immunoglobulin	1	1.1×	0.732
Transcription factor	2	0.6×	0.856

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TAF13	Other/Unknown	no		TFIID_TAF13, Histone-fold
CPAP	Other/Unknown	no		CENPJ_C_dom, TCP10L/CENPJ, Tcp10_C_sf
ASPM	Antibody/Immunoglobulin	yes		IQ_motif_EF-hand-BS, CH_dom, ARM-like
CIT	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, CNH_dom
WDR62	Scaffold/PPI	no		WD40_rpt, Quinoprotein_ADH-like_sf, WD40/YVTN_repeat-like_dom_sf
MCPH1	Other/Unknown	no		BRCT_dom, Microcephalin-like, Microcephalin_mammal
STIL	Other/Unknown	no		STIL, STIL_CC, STIL_N
CDK6	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CDK5RAP2	Other/Unknown	no		Cnn_1N, CDK5RAP2, CDK5RAP2_MYOME_CC
KIF14	Other/Unknown	no		FHA_dom, Kinesin_motor_dom, SMAD_FHA_dom_sf
TEDC1	Other/Unknown	no		TEDC1_dom, TEDC1
COPB2	Scaffold/PPI	no		WD40_rpt, Beta-prop_COPA/B_2nd, WD40/YVTN_repeat-like_dom_sf
KNL1	Other/Unknown	no		Blinkin, Knl1_RWD_C, KNL1_MELT_rpt
METTL5	Other/Unknown	no		DNA_methylase_N6_adenine_CS, Small_mtfrase_dom, SAM-dependent_MTases_sf
SASS6	Other/Unknown	no		SAS-6_N, SAS-6_N_sf, SAS6_CC
TRAPPC14	Other/Unknown	no		TRAPPC14, TRAPP14_C, TRAPP14_N
CEP63	Other/Unknown	no		CEP63/Deup1_N, CEP63/Deup1_CC
MFSD2A	Transporter	yes		MFS_trans_sf, MFS_2
NCAPD3	Other/Unknown	no		ARM-like, NCAPD3, ARM-type_fold
CEP135	Other/Unknown	no		Centriole_BasalBody_StrucProt
ANKLE2	Scaffold/PPI	no		Ankyrin_rpt, LEM_dom, LEM/LEM-like_dom_sf
CEP152	Other/Unknown	no		CEP152/SHC-Transforming, CEP152_CC, CEP152_PLK4_bind
PYCR2	Other/Unknown	no		Pyrroline-COOH_reductase, 6-PGluconate_DH-like_C_sf, P5C_Rdtase_cat_N
PHC1	Transcription factor	no		SAM, Znf_FCS, SAM/pointed_sf
ZNF335	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Zinc_finger/UBP_domain
ANGPT2	Other/Unknown	no		Fibrinogen_a/b/g_C_dom, Fibrinogen_a/b/g_C_1, Fibrinogen_CS
MCPH1-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

24 cohort genes 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)	27
unknown	0

Top tissues across cohort

Tissue	Cohort genes
secondary oocyte	8
oocyte	5
ventricular zone	4
sperm	3
sural nerve	3
right testis	3
granulocyte	3
lateral nuclear group of thalamus	2
left testis	2
calcaneal tendon	2
primordial germ cell in gonad	2
trabecular bone tissue	2
mucosa of transverse colon	2
tendon of biceps brachii	2
parotid gland	2
stromal cell of endometrium	2
male germ line stem cell (sensu Vertebrata) in testis	2
buccal mucosa cell	2
right uterine tube	2
gingival epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TAF13	270	ubiquitous	marker	medial globus pallidus, lateral nuclear group of thalamus, gingival epithelium
CPAP	246	ubiquitous	marker	sperm, left lobe of thyroid gland, right lobe of thyroid gland
ASPM	176	ubiquitous	marker	oocyte, ventricular zone, secondary oocyte
CIT	232	ubiquitous	marker	lateral nuclear group of thalamus, right frontal lobe, sural nerve
WDR62	211	ubiquitous	marker	left testis, right testis, testis
MCPH1	204	ubiquitous	marker	secondary oocyte, ganglionic eminence, calcaneal tendon
STIL	221	ubiquitous	marker	secondary oocyte, oocyte, primordial germ cell in gonad
CDK6	262	ubiquitous	marker	adrenal tissue, trabecular bone tissue, pylorus
CDK5RAP2	272	ubiquitous	marker	sural nerve, ventricular zone, right coronary artery
KIF14	144	ubiquitous	marker	secondary oocyte, endometrium epithelium, trabecular bone tissue
TEDC1	169	ubiquitous	yes	tendon of biceps brachii, granulocyte, mucosa of transverse colon
COPB2	295	ubiquitous	marker	parotid gland, stromal cell of endometrium, type B pancreatic cell
KNL1	193	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, ventricular zone, primordial germ cell in gonad
METTL5	292	ubiquitous	marker	parotid gland, skeletal muscle tissue of biceps brachii, biceps brachii
SASS6	178	ubiquitous	marker	oocyte, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
TRAPPC14	262	ubiquitous	yes	mucosa of transverse colon, granulocyte, right testis
CEP63	282	ubiquitous	marker	calcaneal tendon, colonic epithelium, cortical plate
MFSD2A	220	ubiquitous	marker	right lobe of liver, skin of abdomen, ileal mucosa
NCAPD3	226	ubiquitous	marker	sural nerve, secondary oocyte, ventricular zone
CEP135	238	ubiquitous	marker	amniotic fluid, buccal mucosa cell, sperm
ANKLE2	289	ubiquitous	marker	stromal cell of endometrium, left testis, right testis
CEP152	218	ubiquitous	marker	secondary oocyte, oocyte, sperm
PYCR2	251	ubiquitous	marker	cardiac muscle of right atrium, right uterine tube, left ventricle myocardium
PHC1	252	ubiquitous	marker	right uterine tube, adenohypophysis, pituitary gland
ZNF335	199	ubiquitous	marker	granulocyte, right hemisphere of cerebellum, cerebellar hemisphere
ANGPT2	219	broad	marker	tendon of biceps brachii, popliteal artery, tibial artery
MCPH1-AS1	167	ubiquitous	yes	buccal mucosa cell, oocyte, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 79.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF14	6,868
CDK6	6,767
CIT	5,077
KNL1	3,438
COPB2	2,982
ASPM	2,949
SASS6	2,336
CPAP	2,242
CEP135	2,226
NCAPD3	2,202

Intra-cohort edges

A	B	Sources
ANKLE2	CEP135	string_interaction
ANKLE2	CEP152	string_interaction
ANKLE2	CPAP	string_interaction
ANKLE2	MCPH1	string_interaction
ANKLE2	MFSD2A	string_interaction
ANKLE2	SASS6	string_interaction
ANKLE2	TRAPPC14	string_interaction
ANKLE2	WDR62	string_interaction
ANKLE2	ZNF335	string_interaction
ASPM	CDK5RAP2	string_interaction
ASPM	CEP152	string_interaction
ASPM	CEP63	string_interaction
ASPM	CIT	string_interaction
ASPM	CPAP	string_interaction
ASPM	KIF14	string_interaction
ASPM	MCPH1	string_interaction
ASPM	STIL	string_interaction
ASPM	WDR62	string_interaction
ASPM	ZNF335	string_interaction
CDK5RAP2	CEP135	string_interaction
CDK5RAP2	CEP152	biogrid_interaction, intact, string_interaction
CDK5RAP2	CEP63	string_interaction
CDK5RAP2	CPAP	string_interaction
CDK5RAP2	MCPH1	string_interaction
CDK5RAP2	STIL	string_interaction
CDK5RAP2	WDR62	string_interaction
CDK5RAP2	ZNF335	string_interaction
CDK6	ZNF335	intact
CEP135	CEP152	string_interaction
CEP135	CEP63	string_interaction
CEP135	CPAP	intact, string_interaction
CEP135	MCPH1	string_interaction
CEP135	MFSD2A	string_interaction
CEP135	SASS6	intact, string_interaction
CEP135	STIL	string_interaction
CEP135	WDR62	string_interaction
CEP135	ZNF335	string_interaction
CEP152	CEP63	biogrid_interaction, string_interaction
CEP152	CPAP	string_interaction
CEP152	MCPH1	string_interaction
CEP152	SASS6	biogrid_interaction, string_interaction
CEP152	STIL	string_interaction
CEP152	TRAPPC14	string_interaction
CEP152	WDR62	intact, string_interaction
CEP152	ZNF335	string_interaction
CEP63	CPAP	string_interaction
CEP63	SASS6	string_interaction
CEP63	STIL	string_interaction
CEP63	WDR62	string_interaction
CIT	KIF14	string_interaction

Structural data

PDB: 18 · AlphaFold-only: 8 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TAF13	Q15543	28
CDK6	Q00534	22
MCPH1	Q8NEM0	9
KNL1	Q8NG31	7
ANGPT2	O15123	7
CPAP	Q9HC77	6
STIL	Q15468	5
CDK5RAP2	Q96SN8	4
METTL5	Q9NRN9	3
CEP63	Q96MT8	3
CEP152	O94986	3
COPB2	P35606	2
SASS6	Q6UVJ0	2
CEP135	Q66GS9	2
PYCR2	Q96C36	2
MFSD2A	Q8NA29	1
NCAPD3	P42695	1
PHC1	P78364	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TRAPPC14	Q8WVR3	71.53
CIT	O14578	69.75
KIF14	Q15058	65.68
ANKLE2	Q86XL3	65.14
TEDC1	Q86SX3	63.08
WDR62	O43379	61.19
ZNF335	Q9H4Z2	52.13
ASPM	Q8IZT6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 108. Enrichment computed across 27 evidence-associated genes (19 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 19 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Loss of Nlp from mitotic centrosomes	5	41.7×	4e-06	CPAP, CDK5RAP2, CEP63, CEP135, CEP152
Loss of proteins required for interphase microtubule organization from the centrosome	5	41.7×	4e-06	CPAP, CDK5RAP2, CEP63, CEP135, CEP152
AURKA Activation by TPX2	5	40.1×	4e-06	CPAP, CDK5RAP2, CEP63, CEP135, CEP152
Recruitment of mitotic centrosome proteins and complexes	5	35.8×	6e-06	CPAP, CDK5RAP2, CEP63, CEP135, CEP152
Regulation of PLK1 Activity at G2/M Transition	5	33.4×	6e-06	CPAP, CDK5RAP2, CEP63, CEP135, CEP152
Recruitment of NuMA to mitotic centrosomes	5	30.7×	8e-06	CPAP, CDK5RAP2, CEP63, CEP135, CEP152
Anchoring of the basal body to the plasma membrane	5	29.8×	8e-06	CPAP, CDK5RAP2, CEP63, CEP135, CEP152
Cell Cycle, Mitotic	6	15.2×	2e-05	MCPH1, CDK6, KNL1, CEP63, ANKLE2, CEP152
M Phase	5	17.4×	9e-05	MCPH1, KNL1, CEP63, ANKLE2, CEP152
Cell Cycle	6	11.4×	9e-05	MCPH1, CDK6, KNL1, CEP63, ANKLE2, CEP152
RHO GTPases activate CIT	2	63.3×	0.004	CIT, KIF14
Centrosome maturation	2	26.7×	0.021	CEP63, CEP152
Mitotic Prometaphase	3	10.9×	0.021	KNL1, CEP63, CEP152
Diseases of Cellular Senescence	1	200.3×	0.028	CDK6
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	1	200.3×	0.028	CDK6
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	200.3×	0.028	CDK6
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	1	200.3×	0.028	CDK6
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	200.3×	0.028	CDK6
Diseases of cellular response to stress	1	200.3×	0.028	CDK6
Condensation of Prophase Chromosomes	2	16.5×	0.035	MCPH1, NCAPD3
Drug-mediated inhibition of CDK4/CDK6 activity	1	120.2×	0.043	CDK6
Mitotic G2-G2/M phases	2	13.4×	0.045	CEP63, CEP152
G2/M Transition	2	13.4×	0.045	CEP63, CEP152
Cilium Assembly	2	11.4×	0.058	CEP63, CEP152
Mitotic Metaphase and Anaphase	2	10.2×	0.067	KNL1, ANKLE2
Mitotic Anaphase	2	10.2×	0.067	KNL1, ANKLE2
Signaling by Rho GTPases	3	5.4×	0.068	KIF14, KNL1, ANKLE2
Oxidative Stress Induced Senescence	2	9.5×	0.068	CDK6, PHC1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	3	5.3×	0.068	KIF14, KNL1, ANKLE2
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1	46.2×	0.077	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 26 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
centriole replication	7	197.3×	5e-13	CPAP, WDR62, CDK5RAP2, SASS6, CEP63, CEP135, CEP152
positive regulation of centriole replication	3	388.9×	4e-06	CPAP, STIL, SASS6
positive regulation of spindle assembly	3	243.1×	1e-05	CPAP, STIL, SASS6
cell division	7	12.4×	6e-05	CPAP, CDK6, KIF14, KNL1, CEP63, NCAPD3, ANKLE2
centrosome duplication	3	108.0×	1e-04	STIL, SASS6, CEP152
regulation of mitotic spindle organization	3	97.2×	1e-04	CPAP, STIL, SASS6
cerebral cortex development	4	31.6×	2e-04	ASPM, WDR62, MCPH1, KIF14
positive regulation of neuroblast proliferation	3	67.0×	3e-04	ASPM, WDR62, ZNF335
de novo centriole assembly involved in multi-ciliated epithelial cell differentiation	2	259.3×	6e-04	CEP63, CEP152
positive regulation of establishment of protein localization	2	216.1×	8e-04	CPAP, CEP135
positive regulation of G1/S transition of mitotic cell cycle	3	46.3×	8e-04	CPAP, STIL, SASS6
regulation of mitotic cell cycle spindle assembly checkpoint	2	162.0×	0.001	CDK5RAP2, KNL1
regulation of centrosome cycle	2	144.0×	0.001	WDR62, MCPH1
positive regulation of non-motile cilium assembly	2	144.0×	0.001	CPAP, CEP135
regulation of centriole replication	2	129.6×	0.002	CPAP, STIL
generation of neurons	2	117.8×	0.002	CIT, CDK6
microtubule organizing center organization	2	108.0×	0.002	STIL, CDK5RAP2
regulation of G2/M transition of mitotic cell cycle	2	99.7×	0.002	CDK6, KIF14
regulation of neuron differentiation	2	56.4×	0.007	WDR62, CDK5RAP2
protein localization to centrosome	2	51.9×	0.007	MCPH1, STIL
neuronal stem cell population maintenance	2	51.9×	0.007	ASPM, MCPH1
cerebellar granular layer structural organization	1	648.1×	0.012	KIF14
astral microtubule nucleation	1	648.1×	0.012	CPAP
negative regulation of asymmetric cell division	1	648.1×	0.012	ASPM
negative regulation of positive chemotaxis	1	648.1×	0.012	ANGPT2
lysophospholipid translocation	1	648.1×	0.012	MFSD2A
regulation of phosphatidylethanolamine metabolic process	1	648.1×	0.012	MFSD2A
obsolete regulation of phosphatidylserine metabolic process	1	648.1×	0.012	MFSD2A
regulation of cell maturation	1	648.1×	0.012	KIF14
positive regulation of meiosis I spindle assembly checkpoint	1	648.1×	0.012	KNL1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 24

Druggability breadth: 8 of 27 evidence-associated genes (30%) 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
CIT	MOMELOTINIB
CDK6	PALBOCICLIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDK6	45	4
CIT	41	4
NCAPD3	1	2
TAF13	0	0
CPAP	0	0
ASPM	0	0
WDR62	0	0
MCPH1	0	0
STIL	0	0
CDK5RAP2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	CDK6, CIT
AFATINIB	4	CIT
FEDRATINIB	4	CIT
SORAFENIB	4	CDK6, CIT
RUXOLITINIB	4	CIT
BARICITINIB	4	CIT
VANDETANIB	4	CIT
BOSUTINIB	4	CIT
ABEMACICLIB	4	CDK6, CIT
GILTERITINIB	4	CIT
SUNITINIB	4	CIT
ERLOTINIB	4	CIT
GEFITINIB	4	CIT
PALBOCICLIB	4	CDK6
RIBOCICLIB	4	CDK6
TRILACICLIB	4	CDK6
DABRAFENIB	4	CDK6
OLAPARIB	4	CDK6
VATALANIB	3	CIT
AFURESERTIB	3	CIT
CANERTINIB	3	CIT
FASUDIL	3	CIT
ALVOCIDIB	3	CDK6, CIT
DOVITINIB	3	CDK6, CIT
MOTESANIB	3	CIT
LESTAURTINIB	3	CDK6, CIT
RUBOXISTAURIN	3	CIT
LEROCICLIB	3	CDK6
DINACICLIB	3	CDK6
DALPICICLIB	3	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
CIT	145	Binding:145
NCAPD3	6	Binding:6
PYCR2	2	Binding:2
KIF14	1	Binding:1
COPB2	1	Binding:1
METTL5	1	Binding:1

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
CIT	145
CDK6	715

Pharmacogenomics

Cohort genes with a PharmGKB record: 26; 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)
MOMELOTINIB	4	CDK6, CIT
AFATINIB	4	CIT
FEDRATINIB	4	CIT
SORAFENIB	4	CDK6, CIT
RUXOLITINIB	4	CIT
BARICITINIB	4	CIT
VANDETANIB	4	CIT
BOSUTINIB	4	CIT
ABEMACICLIB	4	CDK6, CIT
GILTERITINIB	4	CIT
SUNITINIB	4	CIT
ERLOTINIB	4	CIT
GEFITINIB	4	CIT
PALBOCICLIB	4	CDK6
RIBOCICLIB	4	CDK6
TRILACICLIB	4	CDK6
DABRAFENIB	4	CDK6
OLAPARIB	4	CDK6
VATALANIB	3	CIT
AFURESERTIB	3	CIT
CANERTINIB	3	CIT
FASUDIL	3	CIT
ALVOCIDIB	3	CDK6, CIT
DOVITINIB	3	CDK6, CIT
MOTESANIB	3	CIT
LESTAURTINIB	3	CDK6, CIT
RUBOXISTAURIN	3	CIT
LEROCICLIB	3	CDK6
DINACICLIB	3	CDK6
DALPICICLIB	3	CDK6

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	CIT, CDK6
B	Phased (≥1) drug, not yet approved	1	NCAPD3
C	Druggable family + PDB, no drug	1	MFSD2A
D	Druggable family + AlphaFold only, no drug	1	ASPM
E	Difficult family or no structure, no drug	22	TAF13, CPAP, WDR62, MCPH1, STIL, CDK5RAP2, KIF14, TEDC1, COPB2, KNL1 (+12 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KIF14	1	CIT
TAF13	0	—
CPAP	0	—
ASPM	0	—
WDR62	0	—
MCPH1	0	—
STIL	0	—
CDK5RAP2	0	—
TEDC1	0	—
COPB2	1	—
KNL1	0	—
METTL5	1	—
SASS6	0	—
TRAPPC14	0	—
CEP63	0	—
MFSD2A	0	—
CEP135	0	—
ANKLE2	0	—
CEP152	0	—
PYCR2	2	—
PHC1	0	—
ZNF335	0	—
ANGPT2	0	—
MCPH1-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.