ELAC2

elaC ribonuclease Z 2, the group of Endoribonucleases|MBL fold containing DNA/RNA interacting subfamily

Basic information

Region (hg38): 17:12991612-13018065

Links

ENSG00000006744 ∙ NCBI:60528 ∙ OMIM:605367 ∙ HGNC:14198 ∙ Uniprot:Q9BQ52 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation defect type 17 (Supportive), mode of inheritance: AR
• combined oxidative phosphorylation defect type 17 (Strong), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR
• combined oxidative phosphorylation defect type 17 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 17	AR	Biochemical; Cardiovascular	The condition can include severe cardiac sequelae, such as hypertrophic cardiomyopathy, and though some individuals have been described as not responding to therapy, others have been reported as benefitting from cardiac surveillance and early insitution of cardioprotective therapy and and biochemical dietary and medical treatment (eg, high-fat diet, coenzyme Q10, riboflavin, thiamine, and carnitine)	Biochemical; Cardiovascular; Neurologic	23849775

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ELAC2 gene.

• Combined oxidative phosphorylation defect type 17 (26 variants)
• not provided (2 variants)
• Prostate cancer, hereditary, 2 (1 variants)
• Prostate cancer, hereditary, 2, susceptibility to (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ELAC2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				213	7	220
missense	1	5	347	7	3	363
nonsense	12	4	2			18
start loss						0
frameshift	14	1	6			21
inframe indel		1	13			14
splice donor/acceptor (+/-2bp)		17	6			23
splice region			20	54	6	80
non coding			9	187	65	261
Total	27	28	383	407	75

Highest pathogenic variant AF is 0.0000657

Variants in ELAC2

This is a list of pathogenic ClinVar variants found in the ELAC2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-12992498-C-T			Benign (Jun 14, 2018)
17-12992538-A-T			Benign (Jun 14, 2018)
17-12992612-G-A			Benign (Jun 23, 2018)
17-12992667-G-C			Benign (Jun 23, 2018)
17-12992785-C-A			Likely benign (Dec 06, 2019)
17-12992819-C-T		Combined oxidative phosphorylation defect type 17	Likely benign (Nov 27, 2023)
17-12992825-GCT-G		Combined oxidative phosphorylation defect type 17	Uncertain significance (Mar 08, 2022)
17-12992832-C-A		Combined oxidative phosphorylation defect type 17	Uncertain significance (Oct 22, 2023)
17-12992832-C-T		Combined oxidative phosphorylation defect type 17	Uncertain significance (Jul 15, 2022)
17-12992834-T-G		Combined oxidative phosphorylation defect type 17	Uncertain significance (May 05, 2022)
17-12992840-G-C		Combined oxidative phosphorylation defect type 17	Uncertain significance (Aug 30, 2021)
17-12992841-C-T		Combined oxidative phosphorylation defect type 17	Uncertain significance (Sep 28, 2022)
17-12992842-C-G		Combined oxidative phosphorylation defect type 17	Uncertain significance (May 24, 2022)
17-12992842-C-T		Combined oxidative phosphorylation defect type 17 • Prostate cancer, hereditary, 2	Likely benign (Jul 15, 2024)
17-12992844-G-A		Combined oxidative phosphorylation defect type 17	Uncertain significance (Mar 08, 2022)
17-12992845-T-C		Combined oxidative phosphorylation defect type 17	Likely benign (Jan 29, 2024)
17-12992847-G-C		Combined oxidative phosphorylation defect type 17	Uncertain significance (Dec 20, 2024)
17-12992850-C-T		Combined oxidative phosphorylation defect type 17	Uncertain significance (Apr 08, 2022)
17-12992851-CTCT-C		Combined oxidative phosphorylation defect type 17	Uncertain significance (Dec 02, 2024)
17-12992864-C-T		Combined oxidative phosphorylation defect type 17	Uncertain significance (Oct 17, 2022)
17-12992865-G-A		Combined oxidative phosphorylation defect type 17 • Inborn genetic diseases	Uncertain significance (Sep 10, 2023)
17-12992869-C-T		Combined oxidative phosphorylation defect type 17	Likely benign (Jul 30, 2024)
17-12992873-T-A		Combined oxidative phosphorylation defect type 17 • Inborn genetic diseases	Uncertain significance (May 23, 2024)
17-12992876-G-A		Combined oxidative phosphorylation defect type 17	Uncertain significance (Sep 01, 2021)
17-12992877-G-A		Combined oxidative phosphorylation defect type 17	Uncertain significance (Feb 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ELAC2	protein_coding	protein_coding	ENST00000338034	24	25797

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.72e-20	0.0771	125450	1	297	125748	0.00119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.410	479	454	1.05	0.0000268	5359
Missense in Polyphen		164	163.82	1.0011		1918
Synonymous	-2.25	219	180	1.21	0.0000114	1605
Loss of Function	1.30	36	45.5	0.792	0.00000236	523

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0111	0.0111
Ashkenazi Jewish	0.00	0.00
East Asian	0.000491	0.000489
Finnish	0.000647	0.000647
European (Non-Finnish)	0.000619	0.000571
Middle Eastern	0.000491	0.000489
South Asian	0.000490	0.000490
Other	0.000823	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Zinc phosphodiesterase, which displays mitochondrial tRNA 3'-processing endonuclease activity. Involved in tRNA maturation, by removing a 3'-trailer from precursor tRNA. {ECO:0000269|PubMed:21593607}.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 17 (COXPD17) [MIM:615440]: An autosomal recessive disorder of mitochondrial dysfunction characterized by onset of severe hypertrophic cardiomyopathy in the first year of life. Other features include hypotonia, poor growth, lactic acidosis, and failure to thrive. The disorder may be fatal in early childhood. {ECO:0000269|PubMed:23849775}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: RNA transport - Homo sapiens (human);tRNA processing;Metabolism of RNA;tRNA processing in the nucleus (Consensus)

Recessive Scores

• pRec: 0.0979

Intolerance Scores

• loftool: 0.929
• rvis_EVS: -0.91
• rvis_percentile_EVS: 10.12

Haploinsufficiency Scores

• pHI: 0.0435
• hipred: N
• hipred_score: 0.231
• ghis: 0.579

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.485

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Elac2
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: tRNA 3'-end processing;mitochondrial tRNA 3'-trailer cleavage, endonucleolytic;mitochondrial tRNA processing
• Cellular component: nucleus;nucleoplasm;mitochondrion;mitochondrial matrix;mitochondrial nucleoid
• Molecular function: RNA binding;endonuclease activity;tRNA-specific ribonuclease activity;metal ion binding