ELAC2

Chr 17AR

elaC ribonuclease Z 2

NCBI Gene: 60528ENSG00000006744UniProt: Q9BQ52

Zinc phosphodiesterase, which displays mitochondrial tRNA 3'-processing endonuclease activity. Involved in tRNA maturation, by removing a 3'-trailer from precursor tRNA (PubMed:21593607). Associates with mitochondrial DNA complexes at the nucleoids to initiate RNA processing and ribosome assembly (PubMed:24703694)

Primary Disease Associations & Inheritance

{Prostate cancer, hereditary, 2, susceptibility to}MIM #614731
Combined oxidative phosphorylation deficiency 17MIM #615440
AR
1289
ClinVar variants
3
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ELAC2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
3 Pathogenic / Likely Pathogenic· 25 VUS of 1289 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.05LOEUF
pLI 0.000
Z-score 1.30
OE 0.79 (0.61–1.05)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.41Z-score
OE missense 1.05 (0.98–1.14)
479 obs / 454.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.79 (0.61–1.05)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.98–1.14)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21
0≤1.21.6
LoF obs/exp: 36 / 45.5Missense obs/exp: 479 / 454.4Syn Z: -2.25

ClinVar Variant Classifications

1289 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
VUS25
Likely Benign68
Benign3
Conflicting1
3
Pathogenic
25
VUS
68
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
3
0
3
Likely Pathogenic
0
0
0
0
0
VUS
0
24
1
0
25
Likely Benign
0
0
40
28
68
Benign
0
0
3
0
3
Conflicting
—1
Total0244728100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ELAC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ELAC2-related infantile hypertrophic cardiomyopathy, lactic acidosis, and isolated complex I deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Prostate cancer, hereditary, 2, susceptibility to}

MIM #614731

Molecular basis of disorder known

Combined oxidative phosphorylation deficiency 17

MIM #615440

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Phenotype and Outcome of Infantile Cardiomyopathy Caused by a Homozygous ELAC2 Mutation.
Shinwari ZMA et al.·Cardiology
2017
Multi-omic profiling reveals an RNA processing rheostat that predisposes to prostate cancer.
Stentenbach M et al.·EMBO Mol Med
2023
Association between RNASEL, MSR1, and ELAC2 single nucleotide polymorphisms and gene expression in prostate cancer risk.
Alvarez-Cubero MJ et al.·Urol Oncol
2016
Association of HPC2/ELAC2 and RNASEL non-synonymous variants with prostate cancer risk in African American familial and sporadic cases.
Robbins CM et al.·Prostate
2008Cohort
Mutations in ELAC2 associated with hypertrophic cardiomyopathy impair mitochondrial tRNA 3'-end processing.
Saoura M et al.·Hum Mutat
2019
HPC2/ELAC2 polymorphisms and prostate cancer risk: analysis by age of onset of disease.
Meitz JC et al.·Br J Cancer
2002
Characterization of linkage disequilibrium structure, mutation history, and tagging SNPs, and their use in association analyses: ELAC2 and familial early-onset prostate cancer.
Camp NJ et al.·Genet Epidemiol
2005
Microcystin-leucine-arginine promotes the development of gallbladder carcinoma via regulating ELAC2.
Gu S et al.·Biochem Biophys Res Commun
2023
Prognostic role of genetic biomarkers in clinical progression of prostate cancer.
Alvarez-Cubero MJ et al.·Exp Mol Med
2015
Ser217Leu polymorphism of the HPC2/ELAC2 gene associated with prostatic cancer risk in Japanese men.
Takahashi H et al.·Int J Cancer
2003
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools