Combined oxidative phosphorylation defect type 17

Summary

Combined oxidative phosphorylation defect type 17 (MONDO:0014190) is a disease caused by ELAC2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ELAC2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 1,067

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		20	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	combined oxidative phosphorylation defect type 17
Mondo ID	MONDO:0014190
OMIM	615440
Orphanet	369913
DOID	DOID:0111496
UMLS	C3809526
MedGen	815856
GARD	0017589
Is cancer (heuristic)	no

Also known as: combined oxidative phosphorylation deficiency 17 · combined oxidative phosphorylation deficiency caused by mutation in ELAC2 · combined oxidative phosphorylation deficiency type 17 · COXPD17 · ELAC2 combined oxidative phosphorylation deficiency

Data availability: 1,067 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › inborn mitochondrial metabolism disorder › mitochondrial oxidative phosphorylation disorder › combined oxidative phosphorylation deficiency › combined oxidative phosphorylation defect type 17

Related subtypes (57): severe X-linked mitochondrial encephalomyopathy, hepatoencephalopathy due to combined oxidative phosphorylation defect type 1, combined oxidative phosphorylation defect type 2, fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3, combined oxidative phosphorylation defect type 4, hypotonia with lactic acidemia and hyperammonemia, combined oxidative phosphorylation defect type 7, combined oxidative phosphorylation defect type 8, combined oxidative phosphorylation defect type 9, mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency, combined oxidative phosphorylation defect type 11, leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome, combined oxidative phosphorylation defect type 13, combined oxidative phosphorylation defect type 14, combined oxidative phosphorylation defect type 15, infantile hypertrophic cardiomyopathy due to MRPL44 deficiency, growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome, combined oxidative phosphorylation deficiency 19, combined oxidative phosphorylation defect type 20, combined oxidative phosphorylation defect type 21, mitochondrial proton-transporting ATP synthase complex deficiency, combined oxidative phosphorylation defect type 23, combined oxidative phosphorylation defect type 24, combined oxidative phosphorylation defect type 25, combined oxidative phosphorylation defect type 26, combined oxidative phosphorylation defect type 27, combined oxidative phosphorylation deficiency 28, combined oxidative phosphorylation deficiency 29, combined oxidative phosphorylation defect type 30, lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome, combined oxidative phosphorylation deficiency 40, combined oxidative phosphorylation deficiency 41, combined oxidative phosphorylation deficiency 42, combined oxidative phosphorylation deficiency 43, combined oxidative phosphorylation deficiency 44, combined oxidative phosphorylation deficiency 52, combined oxidative phosphorylation deficiency 53, combined oxidative phosphorylation deficiency 54, combined oxidative phosphorylation deficiency 37, combined oxidative phosphorylation deficiency 38, combined oxidative phosphorylation deficiency 39, combined oxidative phosphorylation deficiency 45, combined oxidative phosphorylation deficiency 46, combined oxidative phosphorylation deficiency 47, combined oxidative phosphorylation deficiency 48, combined oxidative phosphorylation deficiency 51, combined oxidative phosphorylation deficiency 32, combined oxidative phosphorylation deficiency 33, combined oxidative phosphorylation deficiency 34, combined oxidative phosphorylation deficiency 35, combined oxidative phosphorylation deficiency 36, combined oxidative phosphorylation deficiency 55, combined oxidative phosphorylation deficiency 56, combined oxidative phosphorylation deficiency 57, combined oxidative phosphorylation deficiency 58, combined oxidative phosphorylation deficiency 59, combined oxidative phosphorylation deficiency 60

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

600 retrieved; paginated sample, class counts are floors:

301 uncertain significance, 249 likely benign, 18 pathogenic, 12 conflicting classifications of pathogenicity, 9 benign, 8 likely pathogenic, 2 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070631	NM_018127.7(ELAC2):c.1888C>T (p.Arg630Ter)	ELAC2	Pathogenic	criteria provided, single submitter
1073402	NM_018127.7(ELAC2):c.1435C>T (p.Gln479Ter)	ELAC2	Pathogenic	criteria provided, single submitter
1394254	NM_018127.7(ELAC2):c.1489C>T (p.Arg497Ter)	ELAC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451693	NM_018127.7(ELAC2):c.2179C>T (p.Gln727Ter)	ELAC2	Pathogenic	criteria provided, single submitter
1451714	NM_018127.7(ELAC2):c.1706del (p.Leu569fs)	ELAC2	Pathogenic	criteria provided, single submitter
1455401	NM_018127.7(ELAC2):c.273del (p.Gln92fs)	ELAC2	Pathogenic	criteria provided, single submitter
1456621	NC_000017.10:g.(?12920159)(12920458_?)del	ELAC2	Pathogenic	criteria provided, single submitter
1457297	NM_018127.7(ELAC2):c.766del (p.Val256fs)	ELAC2	Pathogenic	criteria provided, single submitter
1459699	NC_000017.10:g.(?12896135)(12921264_?)del	ELAC2	Pathogenic	criteria provided, single submitter
1954940	NM_018127.7(ELAC2):c.286C>T (p.Gln96Ter)	ELAC2	Pathogenic	criteria provided, single submitter
2014362	NM_018127.7(ELAC2):c.1864G>T (p.Glu622Ter)	ELAC2	Pathogenic	criteria provided, single submitter
2023381	NM_018127.7(ELAC2):c.383T>A (p.Leu128Ter)	ELAC2	Pathogenic	criteria provided, single submitter
2079196	NM_018127.7(ELAC2):c.2144del (p.Met715fs)	ELAC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2115943	NM_018127.7(ELAC2):c.1062C>G (p.Tyr354Ter)	ELAC2	Pathogenic	criteria provided, single submitter
2116681	NM_018127.7(ELAC2):c.1066C>T (p.Gln356Ter)	ELAC2	Pathogenic	criteria provided, single submitter
2147356	NM_018127.7(ELAC2):c.1727dup (p.Leu576fs)	ELAC2	Pathogenic	criteria provided, single submitter
2169867	NM_018127.7(ELAC2):c.1535dup (p.Leu513fs)	ELAC2	Pathogenic	criteria provided, single submitter
2177132	NM_018127.7(ELAC2):c.863_866del (p.Gly288fs)	ELAC2	Pathogenic	criteria provided, single submitter
2196861	NM_018127.7(ELAC2):c.1245del (p.Met416fs)	ELAC2	Pathogenic	criteria provided, single submitter
2577128	NM_018127.7(ELAC2):c.52C>T (p.Gln18Ter)	ELAC2	Pathogenic	criteria provided, multiple submitters, no conflicts
1029514	NM_018127.7(ELAC2):c.1908+1G>A	ELAC2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1475442	NM_018127.7(ELAC2):c.1305-2A>G	ELAC2	Likely pathogenic	criteria provided, single submitter
1484428	NM_018127.7(ELAC2):c.2030-2A>G	ELAC2	Likely pathogenic	criteria provided, single submitter
1490493	NM_018127.7(ELAC2):c.432+1G>A	ELAC2	Likely pathogenic	criteria provided, single submitter
1496568	NM_018127.7(ELAC2):c.246-2A>G	ELAC2	Likely pathogenic	criteria provided, single submitter
1525923	NM_018127.7(ELAC2):c.1080-1G>C	ELAC2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2041575	NM_018127.7(ELAC2):c.2109-6_2111del	ELAC2	Likely pathogenic	criteria provided, single submitter
2152423	NM_018127.7(ELAC2):c.797+1G>A	ELAC2	Likely pathogenic	criteria provided, single submitter
1016087	NM_018127.7(ELAC2):c.591G>A (p.Trp197Ter)	ELAC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1319721	NM_018127.7(ELAC2):c.1808+15C>T	ELAC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
ELAC2	Definitive	Autosomal recessive	combined oxidative phosphorylation defect type 17	4

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	gencc,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).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

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.