Prostate cancer, hereditary, 2

Summary

Prostate cancer, hereditary, 2 (MONDO:0013872) is a cancer with 1 cohort gene.

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 39

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	prostate cancer, hereditary, 2
Mondo ID	MONDO:0013872
OMIM	614731
UMLS	C3539120
MedGen	761328
GARD	0015839
Is cancer (heuristic)	yes

Also known as: ELAC2 familial prostate cancer · familial prostate cancer caused by mutation in ELAC2 · HPC2 · prostate cancer, hereditary, 2 · prostate cancer, hereditary, 2, susceptibility to · prostate cancer, hereditary, type 2

Data availability: 39 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › prostate cancer, hereditary › prostate cancer, hereditary, 2

Related subtypes (17): prostate cancer, hereditary, X-linked 1, prostate cancer, hereditary, X-linked 2, prostate cancer, hereditary, 1, prostate cancer, hereditary, 8, prostate cancer, hereditary, 3, prostate cancer, hereditary, 4, prostate cancer, hereditary, 5, prostate cancer, hereditary, 6, prostate cancer, hereditary, 7, prostate cancer, hereditary, 9, prostate cancer, hereditary, 10, prostate cancer, hereditary, 12, prostate cancer, hereditary, 13, prostate cancer, hereditary, 11, prostate cancer, hereditary, 14, prostate cancer, hereditary, 15, familial 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

ClinVar germline variants

39 retrieved; paginated sample, class counts are floors:

13 benign, 7 uncertain significance, 7 conflicting classifications of pathogenicity, 5 benign/likely benign, 3 likely benign, 2 pathogenic, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1685768	NM_018127.7(ELAC2):c.225C>G (p.Tyr75Ter)	ELAC2	Pathogenic	criteria provided, single submitter
3383145	NM_018127.7(ELAC2):c.225C>A (p.Tyr75Ter)	ELAC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5057	NM_018127.6(ELAC2):c.1641dup (p.His548Alafs)	ELAC2	Pathogenic	criteria provided, single submitter
1029514	NM_018127.7(ELAC2):c.1908+1G>A	ELAC2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
241271	NM_018127.7(ELAC2):c.155C>G (p.Ser52Cys)	ELAC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
415248	NM_018127.7(ELAC2):c.347C>T (p.Ser116Phe)	ELAC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5058	NM_018127.7(ELAC2):c.2342G>A (p.Arg781His)	ELAC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
576991	NM_018127.7(ELAC2):c.1924G>A (p.Val642Met)	ELAC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
698763	NM_018127.7(ELAC2):c.195G>A (p.Ala65=)	ELAC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
845391	NM_018127.7(ELAC2):c.520G>A (p.Glu174Lys)	ELAC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
858177	NM_018127.7(ELAC2):c.2245C>T (p.His749Tyr)	ELAC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1359788	NM_018127.7(ELAC2):c.1865A>G (p.Glu622Gly)	ELAC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2227685	NM_018127.7(ELAC2):c.829G>A (p.Ala277Thr)	ELAC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
225347	NM_018127.7(ELAC2):c.1698+1G>C	ELAC2	Uncertain significance	criteria provided, single submitter
408862	NM_018127.7(ELAC2):c.2375C>T (p.Ala792Val)	ELAC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
474562	NM_018127.7(ELAC2):c.1780C>G (p.Gln594Glu)	ELAC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
541491	NM_018127.7(ELAC2):c.1186A>G (p.Ile396Val)	ELAC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
659632	NM_018127.7(ELAC2):c.1871T>C (p.Leu624Ser)	ELAC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
220685	NM_018127.7(ELAC2):c.2376G>A (p.Ala792=)	ELAC2	Likely benign	criteria provided, multiple submitters, no conflicts
241270	NM_018127.7(ELAC2):c.1479G>C (p.Pro493=)	ELAC2	Benign	criteria provided, multiple submitters, no conflicts
241272	NM_018127.7(ELAC2):c.155C>T (p.Ser52Phe)	ELAC2	Likely benign	criteria provided, multiple submitters, no conflicts
241279	NM_018127.7(ELAC2):c.368-4T>A	ELAC2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
379967	NM_018127.7(ELAC2):c.297-11T>C	ELAC2	Benign	criteria provided, multiple submitters, no conflicts
379968	NM_018127.7(ELAC2):c.1218+15C>T	ELAC2	Benign	criteria provided, multiple submitters, no conflicts
379969	NM_018127.7(ELAC2):c.1304+17A>T	ELAC2	Benign	criteria provided, multiple submitters, no conflicts
379970	NM_018127.7(ELAC2):c.1305-8T>C	ELAC2	Benign	criteria provided, multiple submitters, no conflicts
379971	NM_018127.7(ELAC2):c.1560A>G (p.Thr520=)	ELAC2	Benign	criteria provided, multiple submitters, no conflicts
380021	NM_018127.7(ELAC2):c.491-14T>C	ELAC2	Benign	criteria provided, multiple submitters, no conflicts
380022	NM_018127.7(ELAC2):c.1893A>G (p.Thr631=)	ELAC2	Benign	criteria provided, multiple submitters, no conflicts
380183	NM_018127.7(ELAC2):c.798-20G>T	ELAC2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ELAC2	Orphanet:1331	Familial prostate cancer
ELAC2	Orphanet:369913	Combined oxidative phosphorylation defect type 17

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ELAC2	HGNC:14198	ENSG00000006744	Q9BQ52	Zinc phosphodiesterase ELAC protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ELAC2	Zinc phosphodiesterase ELAC protein 2	Zinc phosphodiesterase, which displays mitochondrial tRNA 3’-processing endonuclease activity.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ELAC2	Enzyme (other)	yes	3.1.26.11	tRNase_Z_dom, RibonucZ/Hydroxyglut_hydro, RNZ2-like

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
apex of heart	1
mucosa of stomach	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ELAC2	286	ubiquitous	marker	adrenal tissue, mucosa of stomach, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ELAC2	2,512

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ELAC2	Q9BQ52	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis	1	3806.7×	0.002	ELAC2
tRNA processing in the mitochondrion	1	2284.0×	0.002	ELAC2
rRNA processing in the mitochondrion	1	1268.9×	0.002	ELAC2
Gene Silencing by RNA	1	356.9×	0.005	ELAC2
tRNA processing	1	356.9×	0.005	ELAC2
tRNA processing in the nucleus	1	196.9×	0.008	ELAC2
rRNA processing	1	146.4×	0.009	ELAC2
Metabolism of RNA	1	41.7×	0.027	ELAC2
Gene expression (Transcription)	1	17.8×	0.056	ELAC2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitochondrial tRNA processing	1	5617.3×	3e-04	ELAC2
mitochondrial tRNA 3’-end processing	1	4213.0×	3e-04	ELAC2
tRNA decay	1	3370.4×	3e-04	ELAC2
tRNA 3’-end processing	1	3370.4×	3e-04	ELAC2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ELAC2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ELAC2	3.1.26.11	tRNase Z

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 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.

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	0
C	Druggable family + PDB, no drug	1	ELAC2
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)
ELAC2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.