Colorectal cancer, susceptibility to, 1

Summary

Colorectal cancer, susceptibility to, 1 (MONDO:0012132) is a cancer with 3 cohort genes (2 CIViC-evidence somatic drivers; 272 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Cohort genes: 3
• ClinVar variants: 272

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	colorectal cancer, susceptibility to, 1
Mondo ID	MONDO:0012132
OMIM	608812
UMLS	C1837315
MedGen	324734
GARD	0027810
Is cancer (heuristic)	yes

Also known as: colorectal cancer caused by mutation in GALNT12 · colorectal cancer, susceptibility to, 1 · colorectal cancer, susceptibility to, type 1 · CRCS1 · GALNT12 colorectal cancer

Data availability: 272 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › colorectal cancer, susceptibility to, 1

Related subtypes (116): mosaic variegated aneuploidy syndrome, 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, 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

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

272 retrieved; paginated sample, class counts are floors:

213 uncertain significance, 28 conflicting classifications of pathogenicity, 18 benign/likely benign, 11 likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1476050	NM_024642.5(GALNT12):c.1418A>G (p.Gln473Arg)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1773953	NM_024642.5(GALNT12):c.149C>T (p.Pro50Leu)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1781265	NM_024642.5(GALNT12):c.1064C>T (p.Thr355Ile)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
220637	NM_024642.5(GALNT12):c.776T>C (p.Val259Ala)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
220845	NM_024642.5(GALNT12):c.566A>G (p.Asn189Ser)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
224569	NM_024642.5(GALNT12):c.907G>A (p.Asp303Asn)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241508	NM_024642.5(GALNT12):c.136_138delinsAGA (p.Gly46Arg)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241518	NM_024642.5(GALNT12):c.889C>T (p.Arg297Trp)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3227895	NM_024642.5(GALNT12):c.104C>G (p.Ser35Trp)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3280550	NM_024642.5(GALNT12):c.759G>A (p.Val253=)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3572304	NM_024642.5(GALNT12):c.*9G>A	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
410578	NM_024642.5(GALNT12):c.608A>G (p.Asn203Ser)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
410579	NM_024642.5(GALNT12):c.1277A>G (p.Lys426Arg)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
410586	NM_024642.5(GALNT12):c.404T>C (p.Leu135Ser)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
410589	NM_024642.5(GALNT12):c.719C>T (p.Pro240Leu)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
410594	NM_024642.5(GALNT12):c.25C>G (p.Arg9Gly)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
416219	NM_024642.5(GALNT12):c.1301C>T (p.Pro434Leu)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
416220	NM_024642.5(GALNT12):c.975G>A (p.Leu325=)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485645	NM_024642.5(GALNT12):c.1655G>A (p.Arg552Lys)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485648	NM_024642.5(GALNT12):c.329G>A (p.Arg110His)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485649	NM_024642.5(GALNT12):c.1339G>A (p.Gly447Arg)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485655	NM_024642.5(GALNT12):c.609C>A (p.Asn203Lys)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485657	NM_024642.5(GALNT12):c.814G>A (p.Gly272Arg)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485665	NM_024642.5(GALNT12):c.212C>T (p.Pro71Leu)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485689	NM_024642.5(GALNT12):c.139G>A (p.Ala47Thr)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
699565	NM_024642.5(GALNT12):c.129C>T (p.Ala43=)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
827561	NM_024642.5(GALNT12):c.829G>A (p.Gly277Ser)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
859404	NM_024642.5(GALNT12):c.171_184del (p.Pro58fs)	GALNT12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
236692	NM_000051.4(ATM):c.2579A>T (p.Asp860Val)	ATM	Uncertain significance	criteria provided, multiple submitters, no conflicts
3367142	NM_007294.4(BRCA1):c.4250T>C (p.Val1417Ala)	BRCA1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 17 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRCA1	LoF	BLCA,BRCA,MEL,OVT	CIViC #6
ATM	LoF	BLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTC	CIViC #69

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
GALNT12	Limited	Autosomal dominant	colorectal cancer, susceptibility to, 1	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRCA1	Orphanet:1331	Familial prostate cancer
BRCA1	Orphanet:1333	Familial pancreatic carcinoma
BRCA1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA1	Orphanet:168829	Primary peritoneal carcinoma
BRCA1	Orphanet:227535	Hereditary breast cancer
BRCA1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA1	Orphanet:694963	Inflammatory breast cancer
BRCA1	Orphanet:70567	Cholangiocarcinoma
BRCA1	Orphanet:84	Fanconi anemia
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
ATM	Orphanet:227535	Hereditary breast cancer
ATM	Orphanet:370109	Ataxia-telangiectasia variant
ATM	Orphanet:440437	Familial colorectal cancer Type X
ATM	Orphanet:52416	Mantle cell lymphoma
ATM	Orphanet:67038	B-cell chronic lymphocytic leukemia

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GALNT12	HGNC:19877	ENSG00000119514	Q8IXK2	Polypeptide N-acetylgalactosaminyltransferase 12	gencc,clinvar
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GALNT12	Polypeptide N-acetylgalactosaminyltransferase 12	Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
ATM	Serine-protein kinase ATM	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.67

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	9.2×	0.313
Enzyme (other)	1	4.0×	0.321
Transcription factor	1	2.8×	0.321

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GALNT12	Enzyme (other)	yes	2.4.1.41	Ricin_B_lectin, Glyco_trans_2-like, Nucleotide-diphossugar_trans
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus epididymis	1
mucosa of sigmoid colon	1
palpebral conjunctiva	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
ventricular zone	1
calcaneal tendon	1
colonic epithelium	1
corpus callosum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GALNT12	232	ubiquitous	marker	palpebral conjunctiva, mucosa of sigmoid colon, corpus epididymis
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRCA1	9,064
ATM	7,383
GALNT12	911

Intra-cohort edges

A	B	Sources
ATM	BRCA1	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRCA1	P38398	33
ATM	Q13315	14
GALNT12	Q8IXK2	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 81. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2	634.4×	1e-04	BRCA1, ATM
Diseases of DNA Double-Strand Break Repair	2	543.8×	1e-04	BRCA1, ATM
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	2	543.8×	1e-04	BRCA1, ATM
Resolution of D-Loop Structures	2	423.0×	1e-04	BRCA1, ATM
Diseases of DNA repair	2	380.7×	1e-04	BRCA1, ATM
DNA Double Strand Break Response	2	317.2×	1e-04	BRCA1, ATM
Impaired BRCA2 binding to PALB2	2	304.5×	1e-04	BRCA1, ATM
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	2	282.0×	1e-04	BRCA1, ATM
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	2	282.0×	1e-04	BRCA1, ATM
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	2	282.0×	1e-04	BRCA1, ATM
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	2	262.5×	1e-04	BRCA1, ATM
Homologous DNA Pairing and Strand Exchange	2	253.8×	1e-04	BRCA1, ATM
Homology Directed Repair	2	205.8×	2e-04	BRCA1, ATM
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	2	205.8×	2e-04	BRCA1, ATM
Impaired BRCA2 binding to RAD51	2	205.8×	2e-04	BRCA1, ATM
Resolution of D-loop Structures through Holliday Junction Intermediates	2	200.3×	2e-04	BRCA1, ATM
HDR through Single Strand Annealing (SSA)	2	195.2×	2e-04	BRCA1, ATM
Meiosis	2	190.3×	2e-04	BRCA1, ATM
Presynaptic phase of homologous DNA pairing and strand exchange	2	181.3×	2e-04	BRCA1, ATM
DNA Double-Strand Break Repair	2	165.5×	2e-04	BRCA1, ATM
Reproduction	2	126.9×	3e-04	BRCA1, ATM
HDR through Homologous Recombination (HRR)	2	126.9×	3e-04	BRCA1, ATM
TP53 Regulates Transcription of DNA Repair Genes	2	120.8×	3e-04	BRCA1, ATM
Nonhomologous End-Joining (NHEJ)	2	112.0×	4e-04	BRCA1, ATM
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	2	97.6×	4e-04	BRCA1, ATM
G2/M Checkpoints	2	89.6×	5e-04	BRCA1, ATM
Regulation of TP53 Activity	2	88.5×	5e-04	BRCA1, ATM
Meiotic recombination	2	86.5×	5e-04	BRCA1, ATM
G2/M DNA damage checkpoint	2	80.1×	6e-04	BRCA1, ATM
Regulation of TP53 Activity through Phosphorylation	2	78.5×	6e-04	BRCA1, ATM

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitotic G2 DNA damage checkpoint signaling	2	295.6×	9e-04	BRCA1, ATM
response to ionizing radiation	2	274.0×	9e-04	BRCA1, ATM
intrinsic apoptotic signaling pathway in response to DNA damage	2	216.1×	1e-03	BRCA1, ATM
double-strand break repair	2	135.4×	0.002	BRCA1, ATM
double-strand break repair via homologous recombination	2	104.0×	0.003	BRCA1, ATM
establishment of RNA localization to telomere	1	2808.7×	0.005	ATM
establishment of protein-containing complex localization to telomere	1	2808.7×	0.005	ATM
positive regulation of telomerase catalytic core complex assembly	1	2808.7×	0.005	ATM
pre-B cell allelic exclusion	1	1872.4×	0.005	ATM
cellular response to nitrosative stress	1	1872.4×	0.005	ATM
regulation of cell cycle	2	49.7×	0.005	BRCA1, ATM
peptidyl-serine autophosphorylation	1	1123.5×	0.006	ATM
cellular response to indole-3-methanol	1	1123.5×	0.006	BRCA1
negative regulation of telomere capping	1	1123.5×	0.006	ATM
regulation of telomere maintenance via telomerase	1	936.2×	0.006	ATM
chordate embryonic development	1	936.2×	0.006	BRCA1
positive regulation of telomere maintenance via telomere lengthening	1	936.2×	0.006	ATM
DNA damage response	2	35.7×	0.006	BRCA1, ATM
lipoprotein catabolic process	1	802.5×	0.006	ATM
negative regulation of centriole replication	1	802.5×	0.006	BRCA1
V(D)J recombination	1	702.2×	0.007	ATM
DNA strand resection involved in replication fork processing	1	702.2×	0.007	BRCA1
meiotic telomere clustering	1	624.1×	0.007	ATM
DNA damage tolerance	1	561.7×	0.007	BRCA1
female meiotic nuclear division	1	561.7×	0.007	ATM
histone mRNA catabolic process	1	561.7×	0.007	ATM
cellular response to X-ray	1	561.7×	0.007	ATM
DNA double-strand break processing	1	510.7×	0.007	ATM
positive regulation of gene expression	2	25.8×	0.007	BRCA1, ATM
homologous recombination	1	468.1×	0.007	BRCA1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
BRCA1	RIBOFLAVIN
ATM	AMIODARONE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATM	35	4
BRCA1	12	4
GALNT12	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ATM, BRCA1
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
CURCUMIN	3	BRCA1
SURAMIN	3	BRCA1
SURAMIN HEXASODIUM	3	BRCA1
DACTOLISIB	3	ATM

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
ATM	240	Binding:233, Functional:5, ADMET:2
BRCA1	13	Binding:9, Functional:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GALNT12	2.4.1.41	polypeptide N-acetylgalactosaminyltransferase
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
ATM	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ATM	240

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ATM, BRCA1
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
CURCUMIN	3	BRCA1
SURAMIN	3	BRCA1
SURAMIN HEXASODIUM	3	BRCA1
DACTOLISIB	3	ATM

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	BRCA1, ATM
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	GALNT12
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GALNT12	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.