Familial prostate carcinoma

Summary

Familial prostate carcinoma (MONDO:0023122) is a cancer with 3 cohort genes (1 CIViC-evidence somatic driver) and 1 clinical trial.

At a glance

• Classification: Cancer
• Cohort genes: 3
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial prostate carcinoma
Mondo ID	MONDO:0023122
NCIT	C103817
UMLS	C4722328
MedGen	1667326
GARD	0004520
Is cancer (heuristic)	yes

Also known as: hereditary prostate carcinoma · prostate cancer, familial · prostate cancer, hereditary

Data availability: 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › prostate carcinoma › familial prostate carcinoma

Related subtypes (8): prostate squamous cell carcinoma, primary prostate urothelial carcinoma, metastatic prostate carcinoma, prostate adenocarcinoma, grade III prostatic intraepithelial neoplasia, prostate small cell carcinoma, hormone-resistant prostate carcinoma, castration-resistant prostate carcinoma

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 28 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
ANTXR1	LoF	LUNG,MEL,STAD,UTUC	CIViC #524

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
ANTXR1	Limited	Autosomal dominant	familial prostate carcinoma	16
ATR	Limited	Autosomal dominant	familial prostate carcinoma	10
MAD1L1	Limited	Unknown	familial prostate carcinoma	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANTXR1	Orphanet:2067	GAPO syndrome
ATR	Orphanet:313846	Familial cutaneous telangiectasia and oropharyngeal cancer predisposition syndrome
ATR	Orphanet:808	Seckel syndrome

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
ANTXR1	HGNC:21014	ENSG00000169604	Q9H6X2	Anthrax toxin receptor 1	gencc
MAD1L1	HGNC:6762	ENSG00000002822	Q9Y6D9	Mitotic spindle assembly checkpoint protein MAD1	gencc
ATR	HGNC:882	ENSG00000175054	Q13535	Serine/threonine-protein kinase ATR	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANTXR1	Anthrax toxin receptor 1	Plays a role in cell attachment and migration.
MAD1L1	Mitotic spindle assembly checkpoint protein MAD1	Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate.
ATR	Serine/threonine-protein kinase ATR	Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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×	0.209
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ANTXR1	Other/Unknown	no		VWF_A, Anthrax_toxin_rcpt_C, Anthrax_toxin_rcpt_extracel
MAD1L1	Other/Unknown	no		Mad1
ATR	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
decidua	1
palpebral conjunctiva	1
stromal cell of endometrium	1
left testis	1
right testis	1
sural nerve	1
Brodmann (1909) area 23	1
adrenal tissue	1
epithelium of nasopharynx	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANTXR1	270	ubiquitous	marker	stromal cell of endometrium, decidua, palpebral conjunctiva
MAD1L1	137	ubiquitous	marker	sural nerve, right testis, left testis
ATR	289	ubiquitous	marker	Brodmann (1909) area 23, epithelium of nasopharynx, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATR	3,541
MAD1L1	2,947
ANTXR1	2,039

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATR	Q13535	10
ANTXR1	Q9H6X2	5
MAD1L1	Q9Y6D9	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 51. 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
Cell Cycle Checkpoints	2	59.0×	0.019	MAD1L1, ATR
Uptake and function of anthrax toxins	1	317.2×	0.035	ANTXR1
Diseases of DNA Double-Strand Break Repair	1	271.9×	0.035	ATR
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	271.9×	0.035	ATR
Diseases of DNA repair	1	190.3×	0.035	ATR
Cellular response to heat stress	1	131.3×	0.035	ATR
Homologous DNA Pairing and Strand Exchange	1	126.9×	0.035	ATR
Homology Directed Repair	1	102.9×	0.035	ATR
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	102.9×	0.035	ATR
Impaired BRCA2 binding to RAD51	1	102.9×	0.035	ATR
Activation of ATR in response to replication stress	1	100.2×	0.035	ATR
HDR through Single Strand Annealing (SSA)	1	97.6×	0.035	ATR
Meiosis	1	95.2×	0.035	ATR
Fanconi Anemia Pathway	1	92.8×	0.035	ATR
Presynaptic phase of homologous DNA pairing and strand exchange	1	90.6×	0.035	ATR
Cell Cycle	2	24.0×	0.035	MAD1L1, ATR
DNA Double-Strand Break Repair	1	82.8×	0.036	ATR
Amplification of signal from the kinetochores	1	65.6×	0.040	MAD1L1
Reproduction	1	63.4×	0.040	ATR
HDR through Homologous Recombination (HRR)	1	63.4×	0.040	ATR
TP53 Regulates Transcription of DNA Repair Genes	1	60.4×	0.040	ATR
Mitotic Spindle Checkpoint	1	52.9×	0.044	MAD1L1
Meiotic synapsis	1	47.0×	0.044	ATR
Regulation of HSF1-mediated heat shock response	1	46.4×	0.044	ATR
G2/M Checkpoints	1	44.8×	0.044	ATR
Regulation of TP53 Activity	1	44.3×	0.044	ATR
G2/M DNA damage checkpoint	1	40.1×	0.044	ATR
Regulation of TP53 Activity through Phosphorylation	1	39.2×	0.044	ATR
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	38.8×	0.044	MAD1L1
Processing of DNA double-strand break ends	1	38.1×	0.044	ATR

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
establishment of RNA localization to telomere	1	2808.7×	0.004	ATR
establishment of protein-containing complex localization to telomere	1	2808.7×	0.004	ATR
positive regulation of telomerase catalytic core complex assembly	1	2808.7×	0.004	ATR
nuclear membrane disassembly	1	1872.4×	0.004	ATR
deactivation of mitotic spindle assembly checkpoint	1	1872.4×	0.004	MAD1L1
negative regulation of extracellular matrix assembly	1	1404.3×	0.005	ANTXR1
regulation of metaphase plate congression	1	1123.5×	0.005	MAD1L1
protein localization to chromosome, telomeric region	1	510.7×	0.008	ATR
positive regulation of mitotic cell cycle spindle assembly checkpoint	1	510.7×	0.008	MAD1L1
response to arsenic-containing substance	1	401.2×	0.008	ATR
attachment of mitotic spindle microtubules to kinetochore	1	351.1×	0.008	MAD1L1
regulation of cellular response to heat	1	351.1×	0.008	ATR
positive regulation of DNA damage response, signal transduction by p53 class mediator	1	330.4×	0.008	ATR
replicative senescence	1	330.4×	0.008	ATR
negative regulation of DNA replication	1	295.6×	0.009	ATR
mitotic G2/M transition checkpoint	1	267.5×	0.009	ATR
positive regulation of telomere maintenance via telomerase	1	244.2×	0.009	ATR
cellular response to gamma radiation	1	200.6×	0.010	ATR
regulation of double-strand break repair	1	193.7×	0.010	ATR
mitotic spindle assembly checkpoint signaling	1	187.2×	0.010	MAD1L1
nucleobase-containing compound metabolic process	1	175.5×	0.011	ATR
positive regulation of epidermal growth factor receptor signaling pathway	1	165.2×	0.011	ANTXR1
interstrand cross-link repair	1	144.0×	0.012	ATR
replication fork processing	1	140.4×	0.012	ATR
DNA damage checkpoint signaling	1	130.6×	0.012	ATR
blood vessel development	1	124.8×	0.012	ANTXR1
substrate adhesion-dependent cell spreading	1	114.6×	0.012	ANTXR1
thymus development	1	112.3×	0.012	MAD1L1
negative regulation of T cell proliferation	1	110.1×	0.012	MAD1L1
response to mechanical stimulus	1	100.3×	0.013	ATR

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATR	8	3
ANTXR1	0	0
MAD1L1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CERALASERTIB	3	ATR
DACTOLISIB	3	ATR
BERZOSERTIB	2	ATR
CAMONSERTIB	2	ATR
TUVUSERTIB	2	ATR
ELIMUSERTIB	1	ATR
M4344	1	ATR
AEW-541	1	ATR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ATR	231	Binding:226, Functional:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATR	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
ATR	231

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

8 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)
CERALASERTIB	3	ATR
DACTOLISIB	3	ATR
BERZOSERTIB	2	ATR
CAMONSERTIB	2	ATR
TUVUSERTIB	2	ATR
ELIMUSERTIB	1	ATR
M4344	1	ATR
AEW-541	1	ATR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	ATR
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	ANTXR1, MAD1L1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ANTXR1	0	—
MAD1L1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02381015	Not specified	COMPLETED	Clinical Validity and Utility of Genomic-targeted Chemoprevention of PCa: Aim 4a