Mosaic variegated aneuploidy syndrome

Summary

Mosaic variegated aneuploidy syndrome (MONDO:0000141) is a disease (an umbrella term covering 7 Mondo subtypes) with 5 cohort genes. The dominant Reactome pathway is Mitotic Prometaphase (4 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 5
• ClinVar variants: 8
• Phenotypes (HPO): 64

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		41	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

64 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000286	Epicanthus	Very frequent (80-99%)
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000501	Glaucoma	Very frequent (80-99%)
HP:0000518	Cataract	Very frequent (80-99%)
HP:0000568	Microphthalmia	Very frequent (80-99%)
HP:0001305	Dandy-Walker malformation	Very frequent (80-99%)
HP:0001541	Ascites	Very frequent (80-99%)
HP:0001561	Polyhydramnios	Very frequent (80-99%)
HP:0002119	Ventriculomegaly	Very frequent (80-99%)
HP:0003560	Muscular dystrophy	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0007957	Corneal opacity	Very frequent (80-99%)
HP:0010880	Increased nuchal translucency	Very frequent (80-99%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000325	Triangular face	Frequent (30-79%)
HP:0000478	Abnormality of the eye	Frequent (30-79%)
HP:0000504	Abnormality of vision	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0000358	Posteriorly rotated ears	Occasional (5-29%)
HP:0000003	Multicystic kidney dysplasia	Occasional (5-29%)
HP:0000062	Ambiguous genitalia	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000340	Sloping forehead	Occasional (5-29%)
HP:0000348	High forehead	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000445	Wide nose	Occasional (5-29%)
HP:0000457	Depressed nasal ridge	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0000821	Hypothyroidism	Occasional (5-29%)
HP:0000924	Abnormality of the skeletal system	Occasional (5-29%)
HP:0000929	Abnormal skull morphology	Occasional (5-29%)
HP:0001000	Abnormality of skin pigmentation	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001360	Holoprosencephaly	Occasional (5-29%)
HP:0001510	Growth delay	Occasional (5-29%)
HP:0001511	Intrauterine growth retardation	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001659	Aortic regurgitation	Occasional (5-29%)
HP:0001679	Abnormal aortic morphology	Occasional (5-29%)
HP:0001680	Coarctation of aorta	Occasional (5-29%)
HP:0001682	Subvalvular aortic stenosis	Occasional (5-29%)
HP:0002007	Frontal bossing	Occasional (5-29%)
HP:0002101	Abnormal lung lobation	Occasional (5-29%)
HP:0002104	Apnea	Occasional (5-29%)
HP:0002247	Duodenal atresia	Occasional (5-29%)
HP:0002664	Neoplasm	Occasional (5-29%)
HP:0002667	Nephroblastoma	Occasional (5-29%)
HP:0002797	Osteolysis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	mosaic variegated aneuploidy syndrome
Mondo ID	MONDO:0000141
MeSH	C536987
OMIM	257300
Orphanet	1052
DOID	DOID:0080688
ICD-11	398235351
SNOMED CT	700056005
UMLS	C4551972
MedGen	1641418
GARD	0003007
Is cancer (heuristic)	no

Also known as: Warburton-Anyane-Yeboa syndrome

Data availability: 8 ClinVar variants · 5 GenCC gene-disease records · 5 cell lines.

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › mosaic variegated aneuploidy syndrome

Related subtypes (116): tuberous sclerosis, hereditary breast ovarian cancer syndrome, hereditary multiple osteochondromas, nevoid basal cell carcinoma syndrome, leukemia, chronic lymphocytic, susceptibility to, 2, blue rubber bleb nevus, cherubism, Beckwith-Wiedemann syndrome, multiple self-healing squamous epithelioma, erythroleukemia, familial, susceptibility to, goiter, multinodular 1, with or without Sertoli-Leydig cell tumors, hyperparathyroidism 2 with jaw tumors, Kaposi sarcoma, susceptibility to, hereditary leiomyomatosis and renal cell cancer, susceptibility to uveal melanoma, melanoma and neural system tumor syndrome, nasopharyngeal carcinoma, susceptibility to, 2, WAGR syndrome, neuroblastoma, susceptibility to, 1, Rothmund-Thomson syndrome, mismatch repair cancer syndrome 1, Wiskott-Aldrich syndrome, N syndrome, hereditary thrombocytopenia and hematologic cancer predisposition syndrome, prostate cancer/brain cancer susceptibility, Brooke-Spiegler syndrome, pancreatic cancer, susceptibility to, 1, Carney-Stratakis syndrome, nasopharyngeal carcinoma, susceptibility to, 1, ovarian cancer, susceptibility to, 1, colorectal cancer, susceptibility to, 1, lung cancer susceptibility 1, leukemia, chronic lymphocytic, susceptibility to, 1, Kostmann syndrome, colorectal cancer, susceptibility to, 2, colorectal cancer, susceptibility to, 3, colorectal cancer, susceptibility to, 5, colorectal cancer, susceptibility to, 6, colorectal cancer, susceptibility to, 7, leukemia, chronic lymphocytic, susceptibility to, 3, leukemia, chronic lymphocytic, susceptibility to, 4, leukemia, chronic lymphocytic, susceptibility to, 5, lung cancer susceptibility 3, colorectal cancer, susceptibility to, 8, colorectal cancer, susceptibility to, 9, colorectal cancer, susceptibility to, 10, colorectal cancer, susceptibility to, 11, lung cancer susceptibility 4, neuroblastoma, susceptibility to, 3, neuroblastoma, susceptibility to, 4, neuroblastoma, susceptibility to, 5, neuroblastoma, susceptibility to, 6, leukemia, acute lymphocytic, susceptibility to, 1, leukemia, acute lymphocytic, susceptibility to, 2, lung cancer susceptibility 5, BAP1-related tumor predisposition syndrome, familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome, Maffucci syndrome, basal cell carcinoma, susceptibility to, 7, colorectal cancer, susceptibility to, 12, leukemia, acute lymphoblastic, susceptibility to, 3, cholangiocarcinoma, susceptibility to, progeroid features-hepatocellular carcinoma predisposition syndrome, neuroblastoma, susceptibility to, 7, DDX41-related hematologic malignancy predisposition syndrome, nasopharyngeal carcinoma, susceptibility to, 3, familial isolated hyperparathyroidism, intestinal polyposis syndrome, dyskeratosis congenita, familial rhabdoid tumor, multiple endocrine neoplasia, hereditary pheochromocytoma-paraganglioma, PTEN hamartoma tumor syndrome, familial multiple fibrofolliculoma, hereditary retinoblastoma, familial atypical multiple mole melanoma syndrome, hereditary nonpolyposis colon cancer, Li-Fraumeni syndrome, Cobb syndrome, neurofibromatosis, susceptibility to familial cutaneous melanoma, pancreatic cancer, susceptibility to, 5, leukemia, acute myeloid, susceptibility to, diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, glioma susceptibility, hemangioma, capillary infantile, susceptibility to, CDH1-related diffuse gastric and lobular breast cancer syndrome, NTHL1-deficiency tumor predisposition syndrome, SAMD9-related spectrum and myeloid neoplasm risk, neuroblastoma, susceptibility to, 2, BARD1-related cancer predisposition, BRCA1-related cancer predisposition, BRCA2-related cancer predisposition, ATM-related cancer predisposition, CHEK2-related cancer predisposition, PALB2-related cancer predisposition, RAD51C-related cancer predisposition, RAD51D-related cancer predisposition, Li-fraumeni-like syndrome, breast cancer, familial, susceptibility to, 1, breast cancer, familial, susceptibility to, 2, breast cancer, familial, susceptibility to, 3, colorectal cancer, susceptibility to, 4, colorectal cancer, susceptibility to, on chromosome 15, ovarian cancer, familial, susceptibility to, 1, ovarian cancer, familial, susceptibility to, 2, ovarian cancer, familial, susceptibility to, 3, inherited hematologic cancer-predisposing syndrome, mosaic neurofibromatosis/schwannomatosis, tumor predisposition syndrome 2, prostate cancer, hereditary, X-linked 3, follicular lymphoma, susceptibility to, GPR161-related medulloblastoma predisposition, SAMD9L-related spectrum and myeloid neoplasm risk, HAVCR2-related cancer predisposition, EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition

Subtypes (7): mosaic variegated aneuploidy syndrome 1, mosaic variegated aneuploidy syndrome 2, mosaic variegated aneuploidy syndrome 3, mosaic variegated aneuploidy syndrome 4, mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition, Atelis syndrome 1, Atelis syndrome 2

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

8 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 1 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
431798	NM_014679.5(CEP57):c.724del (p.Arg242fs)	CEP57	Pathogenic	no assertion criteria provided
1172740	NM_001211.6(BUB1B):c.667C>T (p.Gln223Ter)	BUB1B	Likely pathogenic	criteria provided, single submitter
133779	NM_001211.6(BUB1B):c.1001C>T (p.Pro334Leu)	BUB1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1172748	NM_001211.6(BUB1B):c.698A>G (p.Lys233Arg)	BUB1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1320283	NM_001211.6(BUB1B):c.1083T>G (p.Ser361Arg)	BUB1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
465370	NM_001211.6(BUB1B):c.242A>G (p.Tyr81Cys)	BUB1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
583743	NC_000015.9:g.(?40453416)(40512966_?)dup	BUB1B	Uncertain significance	criteria provided, single submitter
830922	NC_000015.10:g.(?40183704)(40185652_?)del	BUB1B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 31 · Orphanet: 6 · 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
BUB1B	Definitive	Autosomal recessive	mosaic variegated aneuploidy syndrome 1	8
CEP57	Definitive	Autosomal recessive	mosaic variegated aneuploidy syndrome 2	5
TRIP13	Strong	Autosomal recessive	mosaic variegated aneuploidy syndrome 3	10
BUB1	Supportive	Autosomal dominant	mosaic variegated aneuploidy syndrome	7
BUB3	Supportive	Autosomal dominant	mosaic variegated aneuploidy syndrome

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BUB1B	Orphanet:1052	Mosaic variegated aneuploidy syndrome
CEP57	Orphanet:1052	Mosaic variegated aneuploidy syndrome
BUB1	Orphanet:1052	Mosaic variegated aneuploidy syndrome
BUB3	Orphanet:1052	Mosaic variegated aneuploidy syndrome
TRIP13	Orphanet:1052	Mosaic variegated aneuploidy syndrome
TRIP13	Orphanet:654	Nephroblastoma

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BUB1B	HGNC:1149	ENSG00000156970	O60566	Mitotic checkpoint serine/threonine-protein kinase BUB1 beta	gencc,clinvar
CEP57	HGNC:30794	ENSG00000166037	Q86XR8	Centrosomal protein of 57 kDa	gencc,clinvar
BUB1	HGNC:1148	ENSG00000169679	O43683	Mitotic checkpoint serine/threonine-protein kinase BUB1	gencc
BUB3	HGNC:1151	ENSG00000154473	O43684	Mitotic checkpoint protein BUB3	gencc
TRIP13	HGNC:12307	ENSG00000071539	Q15645	Pachytene checkpoint protein 2 homolog	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BUB1B	Mitotic checkpoint serine/threonine-protein kinase BUB1 beta	Essential component of the mitotic checkpoint.
CEP57	Centrosomal protein of 57 kDa	Centrosomal protein which may be required for microtubule attachment to centrosomes.
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.
BUB3	Mitotic checkpoint protein BUB3	Has a dual function in spindle-assembly checkpoint signaling and in promoting the establishment of correct kinetochore-microtubule (K-MT) attachments.
TRIP13	Pachytene checkpoint protein 2 homolog	Plays a key role in chromosome recombination and chromosome structure development during meiosis.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.4

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	2	11.1×	0.036
Scaffold/PPI	1	3.5×	0.386
Other/Unknown	2	0.7×	0.877

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BUB1B	Kinase	yes	2.7.11.1	Kinase-like_dom_sf, Mad3/Bub1_I, Bub1/Mad3
CEP57	Other/Unknown	no		Cep57_MT-bd_dom, Cep57_CLD, Centrosomal_MT-associated
BUB1	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
BUB3	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_PAC1
TRIP13	Other/Unknown	no		ClpA/B, AAA+_ATPase, ATPase_AAA_core

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	2
ventricular zone	2
sperm	2
secondary oocyte	1
calcaneal tendon	1
ganglionic eminence	1
primordial germ cell in gonad	1
epithelium of nasopharynx	1
gingival epithelium	1
bronchial epithelial cell	1
bronchus	1
epithelium of bronchus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BUB1B	210	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
CEP57	292	ubiquitous	marker	oocyte, sperm, calcaneal tendon
BUB1	185	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, ganglionic eminence
BUB3	295	ubiquitous	marker	gingival epithelium, sperm, epithelium of nasopharynx
TRIP13	212	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus

Protein interactions among cohort

Intra-cohort edges: 7.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRIP13	4,676
BUB3	4,326
BUB1B	4,042
BUB1	3,618
CEP57	1,345

Intra-cohort edges

A	B	Sources
BUB1	BUB1B	biogrid_interaction, intact, string_interaction
BUB1	BUB3	biogrid_interaction, intact, string_interaction
BUB1B	BUB3	biogrid_interaction, intact, string_interaction
BUB1B	CEP57	string_interaction
BUB1B	TRIP13	string_interaction
BUB3	TRIP13	string_interaction
CEP57	TRIP13	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BUB1B	O60566	9
BUB1	O43683	9
TRIP13	Q15645	6
CEP57	Q86XR8	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BUB3	O43684	96.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 40. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitotic Prometaphase	4	69.2×	1e-06	BUB1B, CEP57, BUB1, BUB3
M Phase	4	66.0×	1e-06	BUB1B, CEP57, BUB1, BUB3
Cell Cycle, Mitotic	4	48.2×	2e-06	BUB1B, CEP57, BUB1, BUB3
Amplification of signal from the kinetochores	3	147.7×	5e-06	BUB1B, BUB1, BUB3
Cell Cycle	4	36.0×	5e-06	BUB1B, CEP57, BUB1, BUB3
Mitotic Spindle Checkpoint	3	119.0×	6e-06	BUB1B, BUB1, BUB3
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	3	87.4×	1e-05	BUB1B, BUB1, BUB3
Mitotic Metaphase and Anaphase	3	72.6×	2e-05	BUB1B, BUB1, BUB3
Mitotic Anaphase	3	72.6×	2e-05	BUB1B, BUB1, BUB3
EML4 and NUDC in mitotic spindle formation	3	69.6×	2e-05	BUB1B, BUB1, BUB3
Cell Cycle Checkpoints	3	66.4×	2e-05	BUB1B, BUB1, BUB3
Resolution of Sister Chromatid Cohesion	3	64.9×	2e-05	BUB1B, BUB1, BUB3
RHO GTPases Activate Formins	3	58.3×	3e-05	BUB1B, BUB1, BUB3
RHO GTPase Effectors	3	51.0×	4e-05	BUB1B, BUB1, BUB3
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	2	317.2×	4e-05	BUB1B, BUB3
Separation of Sister Chromatids	3	45.6×	4e-05	BUB1B, BUB1, BUB3
Inactivation of APC/C via direct inhibition of the APC/C complex	2	259.6×	5e-05	BUB1B, BUB3
APC-Cdc20 mediated degradation of Nek2A	2	211.5×	7e-05	BUB1B, BUB3
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	2	211.5×	7e-05	BUB1B, BUB3
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	2	203.9×	7e-05	BUB1B, BUB3
APC/C:Cdc20 mediated degradation of mitotic proteins	2	178.4×	9e-05	BUB1B, BUB3
APC/C-mediated degradation of cell cycle proteins	2	167.9×	9e-05	BUB1B, BUB3
Regulation of mitotic cell cycle	2	167.9×	9e-05	BUB1B, BUB3
Regulation of APC/C activators between G1/S and early anaphase	2	154.3×	1e-04	BUB1B, BUB3
Signaling by Rho GTPases	3	25.6×	2e-04	BUB1B, BUB1, BUB3
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	3	25.1×	2e-04	BUB1B, BUB1, BUB3
Cdc20:Phospho-APC/C mediated degradation of Cyclin A	2	86.5×	3e-04	BUB1B, BUB3
Signal Transduction	3	7.6×	0.005	BUB1B, BUB1, BUB3
Centrosome maturation	1	63.4×	0.022	CEP57
Loss of Nlp from mitotic centrosomes	1	39.6×	0.032	CEP57

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitotic spindle assembly checkpoint signaling	4	449.4×	1e-09	BUB1B, BUB1, BUB3, TRIP13
meiotic sister chromatid cohesion, centromeric	2	1348.2×	9e-06	BUB1B, BUB1
cell division	3	27.7×	8e-04	BUB1B, BUB1, BUB3
regulation of sister chromatid cohesion	1	3370.4×	0.002	BUB1
positive regulation of maintenance of mitotic sister chromatid cohesion, centromeric	1	3370.4×	0.002	BUB1
spermatid development	2	58.1×	0.002	CEP57, TRIP13
meiotic recombination checkpoint signaling	1	1123.5×	0.003	TRIP13
metaphase/anaphase transition of mitotic cell cycle	1	421.3×	0.006	BUB1B
protein localization to chromosome, centromeric region	1	421.3×	0.006	BUB1B
female meiosis I	1	374.5×	0.006	TRIP13
regulation of chromosome segregation	1	374.5×	0.006	BUB1
protein localization to kinetochore	1	280.9×	0.008	BUB3
attachment of spindle microtubules to kinetochore	1	187.2×	0.011	BUB3
synaptonemal complex assembly	1	129.6×	0.014	TRIP13
oocyte maturation	1	120.4×	0.014	TRIP13
male meiosis I	1	116.2×	0.014	TRIP13
reciprocal meiotic recombination	1	112.3×	0.014	TRIP13
apoptotic process	2	11.5×	0.016	BUB1B, BUB1
oogenesis	1	76.6×	0.018	TRIP13
fibroblast growth factor receptor signaling pathway	1	57.1×	0.023	CEP57
meiotic cell cycle	1	48.9×	0.025	BUB3
double-strand break repair	1	40.6×	0.029	TRIP13
chromosome segregation	1	34.8×	0.032	BUB1
protein homooligomerization	1	24.4×	0.044	CEP57
transcription by RNA polymerase II	1	14.1×	0.072	TRIP13
spermatogenesis	1	7.0×	0.134	TRIP13

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 5 evidence-associated genes (80%) 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
BUB1B	CERITINIB
BUB1	GILTERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BUB1	10	4
BUB1B	1	4
CEP57	0	0
BUB3	0	0
TRIP13	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CERITINIB	4	BUB1B
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): 2.

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

Symbol	Assays	Type breakdown
BUB1	86	Binding:84, Functional:2
BUB1B	12	Binding:12
TRIP13	9	Binding:9
BUB3	7	Binding:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BUB1B	2.7.11.1	non-specific serine/threonine protein kinase
BUB1	2.7.11.1	non-specific serine/threonine protein kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

11 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)
CERITINIB	4	BUB1B
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)	2	BUB1B, 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	3	CEP57, BUB3, TRIP13

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CEP57	0	BUB1B
BUB3	7	BUB1B, BUB1
TRIP13	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.