ELAC2

Summary

ELAC2 (elaC ribonuclease Z 2, HGNC:14198) is a protein-coding gene on chromosome 17p12, encoding Zinc phosphodiesterase ELAC protein 2 (Q9BQ52). Zinc phosphodiesterase, which displays mitochondrial tRNA 3’-processing endonuclease activity. It is a common-essential gene (DepMap: required in 95.8% of cancer cell lines).

The protein encoded by this gene has a C-terminal domain with tRNA 3′ processing endoribonuclease activity, which catalyzes the removal of the 3’ trailer from precursor tRNAs. The protein also interacts with activated Smad family member 2 (Smad2) and its nuclear partner forkhead box H1 (also known as FAST-1), and reduced expression can suppress transforming growth factor-beta induced growth arrest. Mutations in this gene result in an increased risk of prostate cancer. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 60528 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 1,275 total — 50 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 15
• Cancer dependency (DepMap): dependent in 95.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_018127

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14198
Approved symbol	ELAC2
Name	elaC ribonuclease Z 2
Location	17p12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10530, HPC2
Ensembl gene	ENSG00000006744
Ensembl biotype	protein_coding
OMIM	605367
Entrez	60528

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 31 protein_coding, 8 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000338034, ENST00000395962, ENST00000426905, ENST00000446899, ENST00000465825, ENST00000476042, ENST00000480891, ENST00000484122, ENST00000487229, ENST00000491478, ENST00000492559, ENST00000578071, ENST00000578104, ENST00000578991, ENST00000580504, ENST00000581499, ENST00000583371, ENST00000584650, ENST00000609101, ENST00000609345, ENST00000609757, ENST00000860246, ENST00000860247, ENST00000860248, ENST00000860249, ENST00000860250, ENST00000860251, ENST00000860252, ENST00000860253, ENST00000860254, ENST00000923771, ENST00000923772, ENST00000923773, ENST00000923774, ENST00000923775, ENST00000923776, ENST00000961320, ENST00000961321, ENST00000961322, ENST00000961323, ENST00000961324

RefSeq mRNA: 3 — MANE Select: NM_018127 NM_001165962, NM_018127, NM_173717

CCDS: CCDS11164, CCDS54093

Canonical transcript exons

ENST00000338034 — 24 exons

Exon	Start	End
ENSE00002703380	13017703	13018027
ENSE00003464261	13002274	13002359
ENSE00003465223	13003479	13003574
ENSE00003491740	12991612	12993045
ENSE00003492207	13005753	13005825
ENSE00003501716	12994963	12995062
ENSE00003515264	12993687	12993831
ENSE00003530024	12995703	12995812
ENSE00003534040	13014439	13014496
ENSE00003547137	13004989	13005101
ENSE00003564930	13002441	13002579
ENSE00003568774	12995940	12995978
ENSE00003576410	13013207	13013275
ENSE00003581012	12994764	12994884
ENSE00003590973	13000156	13000274
ENSE00003597202	13005921	13005979
ENSE00003628255	13010613	13010671
ENSE00003634733	12994425	12994503
ENSE00003644804	12996547	12996685
ENSE00003703301	13016862	13016932
ENSE00003706858	13015768	13015832
ENSE00003710104	13017071	13017121
ENSE00003786727	12998412	12998508
ENSE00003790069	13011663	13011782

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 96.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.2946 / max 192.5078, expressed in 1821 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164643	36.5821	1818
164639	1.4800	942
164642	0.5117	160
164640	0.3492	174
164641	0.2365	91
164638	0.1352	38

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	96.00	gold quality
mucosa of stomach	UBERON:0001199	95.90	gold quality
apex of heart	UBERON:0002098	95.53	gold quality
right adrenal gland cortex	UBERON:0035827	94.96	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.84	gold quality
lower esophagus	UBERON:0013473	94.81	gold quality
right adrenal gland	UBERON:0001233	94.78	gold quality
left adrenal gland	UBERON:0001234	94.71	gold quality
sural nerve	UBERON:0015488	94.63	gold quality
left adrenal gland cortex	UBERON:0035825	94.45	gold quality
gastrocnemius	UBERON:0001388	94.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.39	gold quality
adrenal gland	UBERON:0002369	94.22	gold quality
muscle of leg	UBERON:0001383	94.21	gold quality
colonic epithelium	UBERON:0000397	94.08	gold quality
adrenal cortex	UBERON:0001235	93.91	gold quality
heart left ventricle	UBERON:0002084	93.79	gold quality
esophagus	UBERON:0001043	93.57	gold quality
islet of Langerhans	UBERON:0000006	93.52	gold quality
cardiac ventricle	UBERON:0002082	93.48	gold quality
rectum	UBERON:0001052	93.42	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.41	gold quality
skin of leg	UBERON:0001511	93.31	gold quality
body of stomach	UBERON:0001161	93.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.09	gold quality
right atrium auricular region	UBERON:0006631	93.00	gold quality
smooth muscle tissue	UBERON:0001135	92.98	gold quality
popliteal artery	UBERON:0002250	92.90	gold quality
tibial artery	UBERON:0007610	92.90	gold quality
skin of abdomen	UBERON:0001416	92.85	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.65
E-MTAB-7303	no	864.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EED, RBPJ

miRNA regulators (miRDB)

34 targeting ELAC2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-9898	99.00	67.89	500
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-7154-3P	97.65	65.02	985
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-6839-5P	96.74	68.29	1088

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 95.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 31)

• ELAC2 harbors mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two Utah pedigrees (PMID:11175785)
• variation in the putative prostate cancer susceptibility gene ELAC2 contributes to the elevated risk of prostate cancer in Afro-Caribbean males from Tobago (PMID:12384782)
• Meta-analysis of associations of the Ser217Leu and Ala541Thr variants in ELAC2 (HPC2) and prostate cancer (PMID:12515253)
• Although the Leu217 and Thr541 variants of ELAC2 are less common in Japanese than in Caucasians, both variants confer significantly increased risk of prostate cancer in Japanese. (PMID:12522685)
• ELAC2 interacts with the gamma-tubulin complex and perturbation of ELAC2 might promote tumorigenesis through irregular cell division (PMID:12569551)
• There is no evidence that either ELAC2 polymorphism is associated with prostate cancer or PSA level. (PMID:12783937)
• polymorphism of the ELAC2 gene is associated with prostatic cancer risk in Japanese men (PMID:12949798)
• When considering joint genotypes, white men homozygous for the Leu217 variant on an Ala541/Ala541 background had an increased risk of prostate cancer [odds ratio (OR)=1.84; 95% confidence interval (CI), 1.11-3.06]. (PMID:14504198)
• ELAC2 has a role in prostate cancer (PMID:14625808)
• Thr allele at 541 in HPC2/ELAC2 has strong significance in the predisposition of sporadic Pca in Japan. (PMID:15368467)
• Single nucleotide polymorphisms associated with hereditary prostate cancer. (PMID:16114055)
• candidate prostate cancer susceptibility gene ELAC2 potentiates TGF-beta/Smad-induced transcriptional responses (PMID:16636667)
• The oncogenic role of HPC2 in human primary breast carcinomas is determined by its capacity to inhibit INK4a/ARF proteins(p16INK4a, p14ARF, or h-TERT) or to induce telomerase activity. (PMID:17145810)
• Common SNPs and haplotypes of ELAC2 are associated with risk of aggressive prostate cancer. (PMID:18375959)
• Changes in K(M) observed with some of the substitutions suggest contacts between tRNase Z and substrate tRNA in this region, and changes in tRNA structure provide an additional basis for interpretation of the kinetic effects.[tRNase Z] (PMID:18421255)
• HPC2/ELAC2 and RNASEL may play a role, however minor, in prostate cancer risk among African American men. (PMID:18767027)
• The findings reveal that 3’ end processing is a limiting step for defective tRNA maturation and demonstrate that overexpression of ELAC2 can promote defective tRNA 3’ processing in vivo. (PMID:19555350)
• The present data suggest the possibility that human cytosolic tRNase ZL modulates gene expression through a subset of microRNAs in the cells. (PMID:19751732)
• Our findings corroborate the involvement of ELAC2, MSR1, and RNASEL in the etiology of prostate cancer even in individuals without a family history. (PMID:20086112)
• Data describe polymorphisms in the HPC/ELAC-2 and alpha 1-antitrypsin genes that correlate with human diseases in an Indian population. (PMID:20119870)
• ELAC2 polymorphisms are associated with prostate cancer. (PMID:20231859)
• analysis of dual nuclear/mitochondrial targeting of the ELAC2 gene product by alternative translation initiation (PMID:21559454)
• results indicate that ELAC2 functions as a tRNase Z in human mitochondria and suggest that mt-tRNase Z preferentially cleaves molecules already processed by the proteinaceous mtRNase P (PMID:21593607)
• ELAC2 and PTCD1 affect the 3’ end processing of tRNAs. (PMID:21857155)
• ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy. (PMID:23849775)
• ELAC2 rs11545302 polymorphism was associated with PSA > 20 and rs4792311 was associated with TNM > 2. (PMID:27318894)
• A homozygous splicing mutation in ELAC2 suggests phenotypic variability including intellectual disability with minimal cardiac involvement (PMID:27769300)
• This study describes the cardiac phenotype and outcome of ELAC2 mutation in Infantile Cardiomyopathy (PMID:28441660)
• Our study thus broadly confirms the correlation of ELAC2 variants with severe infantile-onset forms of HCM and mitochondrial respiratory chain dysfunction. (PMID:31045291)
• A Study of Ser217Leu and Ala541Thr Polymorphism in the Men Afflicted with Prostate Cancer and in the Men being Suspicious of Prostate Cancer. (PMID:32592348)
• ELAC2 is a functional prostate cancer risk allele. (PMID:37353407)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	elac2	ENSDARG00000034060
mus_musculus	Elac2	ENSMUSG00000020549
rattus_norvegicus	Elac2	ENSRNOG00000003424
drosophila_melanogaster	RNaseZ	FBGN0028426

Paralogs (1): ELAC1 (ENSG00000141642)

Protein

Protein identifiers

Zinc phosphodiesterase ELAC protein 2 — Q9BQ52 (reviewed: Q9BQ52)

Alternative names: ElaC homolog protein 2, Heredity prostate cancer protein 2, Ribonuclease Z 2, tRNA 3 endonuclease 2, tRNase Z 2

All UniProt accessions (12): Q9BQ52, A0A0S2Z5M8, E7ES68, G5E9D5, H7C2I4, J3QL08, J3QLK4, J3QQT1, J3QRS2, V9GYS7, V9GYU5, V9GZ72

UniProt curated annotations — full annotation on UniProt →

Function. Zinc phosphodiesterase, which displays mitochondrial tRNA 3’-processing endonuclease activity. Involved in tRNA maturation, by removing a 3’-trailer from precursor tRNA. Associates with mitochondrial DNA complexes at the nucleoids to initiate RNA processing and ribosome assembly.

Subunit / interactions. Homodimer. Interacts with PTCD1.

Subcellular location. Mitochondrion. Mitochondrion matrix. Mitochondrion nucleoid. Nucleus.

Tissue specificity. Widely expressed. Highly expressed in heart, placenta, liver, skeletal muscle, kidney, pancreas, testis and ovary. Weakly expressed in brain, lung, spleen, thymus, prostate, small intestine, colon and leukocytes.

Disease relevance. Prostate cancer, hereditary, 2 (HPC2) [MIM:614731] A condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the RNase Z family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BQ52-1	1	yes
Q9BQ52-2	2
Q9BQ52-3	3
Q9BQ52-4	4

RefSeq proteins (3): NP_001159434, NP_060597, NP_776065 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027794	tRNase_Z_dom	Domain
IPR036866	RibonucZ/Hydroxyglut_hydro	Homologous_superfamily
IPR047151	RNZ2-like	Family

Pfam: PF13691, PF23023

Enzyme classification (BRENDA):

• EC 3.1.26.11 — tRNase Z (BRENDA: 80 organisms, 232 substrates, 22 inhibitors, 76 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

53 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BIS(P-NITROPHENYL)PHOSPHATE	1.2–22.2	9
PRE-TRNA(ARG1)	0.0003–0.0009	6
TRNA(HIS48)	—	4
PRE-TRNA(ARG2)	0.0003–0.0006	3
PRE-TRNAHIS	—	3
PRE-TRNAARG	—	2
R-L0	0.0008	2
PRE-TRNA(ARG)	—	1
PRE-TRNA(VAL)	—	1
PRE-TRNAGLU-CCUN17	0.0005	1
PRE-TRNAGLU-CUAN17	0.0015	1
PRE-TRNAGLU-UUAN17	0.001	1
PRE-TRNAGLY	—	1
PRE-TRNAHIS-AUG	—	1
PRE-TRNAHIS-CCA	—	1

UniProt features (112 total): strand 37, helix 32, sequence variant 13, modified residue 6, turn 6, splice variant 6, sequence conflict 4, region of interest 3, compositionally biased region 3, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
9EY0	ELECTRON MICROSCOPY	2.78
8CBL	ELECTRON MICROSCOPY	2.79
9EY1	ELECTRON MICROSCOPY	2.9
8RR1	ELECTRON MICROSCOPY	2.93
9EY2	ELECTRON MICROSCOPY	2.96
8Z0P	ELECTRON MICROSCOPY	3.1
8RR4	ELECTRON MICROSCOPY	3.2
8RR3	ELECTRON MICROSCOPY	3.4
8Z1G	ELECTRON MICROSCOPY	3.7
8Z1F	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQ52-F1	82.81	0.63

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 212, 229, 618, 736, 199, 208

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-6784531	tRNA processing in the nucleus
R-HSA-6785470	tRNA processing in the mitochondrion
R-HSA-8868766	rRNA processing in the mitochondrion
R-HSA-9708296	tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis
R-HSA-211000	Gene Silencing by RNA
R-HSA-72306	tRNA processing
R-HSA-72312	rRNA processing
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 196 (showing top): chr17p12, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, PUJANA_CHEK2_PCC_NETWORK, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, MODULE_66, MUELLER_PLURINET, GOMF_RNA_ENDONUCLEASE_ACTIVITY, ICHIBA_GRAFT_VERSUS_HOST_DISEASE_35D_DN

GO Biological Process (5): tRNA decay (GO:0016078), tRNA 3’-end processing (GO:0042780), mitochondrial tRNA processing (GO:0090646), mitochondrial tRNA 3’-end processing (GO:1990180), tRNA processing (GO:0008033)

GO Molecular Function (8): RNA binding (GO:0003723), RNA endonuclease activity (GO:0004521), tRNA-specific ribonuclease activity (GO:0004549), 3’-tRNA processing endoribonuclease activity (GO:0042781), metal ion binding (GO:0046872), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), mitochondrial nucleoid (GO:0042645)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
tRNA processing	2
Metabolism of RNA	2
rRNA processing	1
Gene Silencing by RNA	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
tRNA metabolic process	2
tRNA processing	2
tRNA 3’-end processing	2
RNA nuclease activity	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
RNA catabolic process	1
RNA 3’-end processing	1
mitochondrial RNA metabolic process	1
mitochondrial RNA processing	1
mitochondrial RNA 3’-end processing	1
mitochondrial tRNA processing	1
RNA processing	1
nucleic acid binding	1
endonuclease activity	1
catalytic activity, acting on a tRNA	1
tRNA-specific ribonuclease activity	1
RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism	1
cation binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
catalytic activity	1
nuclear lumen	1
intracellular organelle lumen	1
mitochondrial matrix	1
nucleoid	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2252 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELAC2	DCLRE1A	Q6PJP8	822
ELAC2	TRMT10C	Q7L0Y3	775
ELAC2	CPSF3	Q9UKF6	774
ELAC2	RNASEL	Q05823	759
ELAC2	PRORP	O15091	722
ELAC2	TRNT1	Q96Q11	716
ELAC2	MSR1	P21757	713
ELAC2	SUPV3L1	Q8IYB8	660
ELAC2	SRD5A2	P31213	643
ELAC2	GTPBP3	Q969Y2	641
ELAC2	MTO1	Q9Y2Z2	640
ELAC2	MTPAP	Q9NVV4	635
ELAC2	HSD17B10	Q99714	610
ELAC2	PNPT1	Q8TCS8	608
ELAC2	PTCD1	O75127	588

IntAct

53 interactions, top by confidence:

A	B	Type	Score
ELAC2	RNF123	psi-mi:“MI:0914”(association)	0.640
YBEY	NME4	psi-mi:“MI:0914”(association)	0.530
UQCRFS1	NDUFAB1	psi-mi:“MI:0914”(association)	0.530
	ELAC2	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Bag2		psi-mi:“MI:0914”(association)	0.350
CAMKK1		psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
YBEY	NUDT19	psi-mi:“MI:0914”(association)	0.350
MRPL21		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
DNAJC7	HSPA8	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
MALSU1	VWA8	psi-mi:“MI:0914”(association)	0.350
PFDN5	GTPBP10	psi-mi:“MI:0914”(association)	0.350
MRPL21	FDXR	psi-mi:“MI:0914”(association)	0.350
NTNG1	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPS24	VWA8	psi-mi:“MI:0914”(association)	0.350
AMACR	VWA8	psi-mi:“MI:0914”(association)	0.350
NDUFS7	NUDT19	psi-mi:“MI:0914”(association)	0.350
MRPS2	POLRMT	psi-mi:“MI:0914”(association)	0.350
BAG5	ACACB	psi-mi:“MI:0914”(association)	0.350
MYL10	BCKDK	psi-mi:“MI:0914”(association)	0.350
BHLHA15	RNASEH1	psi-mi:“MI:0914”(association)	0.350
GLYATL1	HSPD1	psi-mi:“MI:0914”(association)	0.350
ELAC2	BAG2	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (207): ELAC2 (Affinity Capture-MS), C12orf10 (Co-fractionation), CKAP5 (Co-fractionation), DDX5 (Co-fractionation), DNAJC17 (Co-fractionation), EIF2D (Co-fractionation), EIF6 (Co-fractionation), ELAC2 (Co-fractionation), FERMT2 (Co-fractionation), GLRX5 (Co-fractionation), GORASP2 (Co-fractionation), HARS (Co-fractionation), HNRNPF (Co-fractionation), HNRNPH1 (Co-fractionation), HNRNPK (Co-fractionation)

ESM2 similar proteins: A0A5F8AH41, A0AVI4, A0JMH2, A1Y9I9, A5WVX1, B0X4N1, B4P925, D3ZX08, O55171, O88512, O95050, O97972, P0DPD7, P0DPE0, P0DPE1, P10937, P10938, P11086, P40935, P40936, Q06AU9, Q08DK0, Q14CH7, Q32PE2, Q32Q92, Q3SZG9, Q3URQ7, Q568P9, Q5E9L5, Q5JTZ9, Q5RCH4, Q5RFR7, Q6NTR1, Q6NZB1, Q7QIL2, Q7TMC8, Q80YU0, Q8HY87, Q8K304, Q8NFF5

Diamond homologs: A0RYQ9, B6IRV8, P36159, P87168, Q10155, Q1DEJ2, Q5HP47, Q80Y81, Q8CGS5, Q8HY87, Q8MKW7, Q9BQ52, Q9GL72, Q9GL73, Q9YAV8, A6LFA6, B1WQW1, B9KYQ3, Q1IA50, Q49XV1, Q8VYS2, B2RIU4, Q51834, A8ABB4, B9LQT0, D4GZ88, A2C4C2, A7MHT9, A8ADW5, B0JGG3, B1IAL2, B2IMY3, B5E2R6, B7K1N1, B7K762, B8ZMQ6, C1C636, C1CD41, C1CJE0, C1CQF2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial ribosome-associated quality control	6	13.9×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	6	10.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1275 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	50
Likely pathogenic	26
Uncertain significance	446
Likely benign	593
Benign	86

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070631	NM_018127.7(ELAC2):c.1888C>T (p.Arg630Ter)	Pathogenic
1073402	NM_018127.7(ELAC2):c.1435C>T (p.Gln479Ter)	Pathogenic
1451693	NM_018127.7(ELAC2):c.2179C>T (p.Gln727Ter)	Pathogenic
1451714	NM_018127.7(ELAC2):c.1706del (p.Leu569fs)	Pathogenic
1455401	NM_018127.7(ELAC2):c.273del (p.Gln92fs)	Pathogenic
1456621	NC_000017.10:g.(?12920159)(12920458_?)del	Pathogenic
1457297	NM_018127.7(ELAC2):c.766del (p.Val256fs)	Pathogenic
1459699	NC_000017.10:g.(?12896135)(12921264_?)del	Pathogenic
1685768	NM_018127.7(ELAC2):c.225C>G (p.Tyr75Ter)	Pathogenic
1954940	NM_018127.7(ELAC2):c.286C>T (p.Gln96Ter)	Pathogenic
2014362	NM_018127.7(ELAC2):c.1864G>T (p.Glu622Ter)	Pathogenic
2023381	NM_018127.7(ELAC2):c.383T>A (p.Leu128Ter)	Pathogenic
2115943	NM_018127.7(ELAC2):c.1062C>G (p.Tyr354Ter)	Pathogenic
2116681	NM_018127.7(ELAC2):c.1066C>T (p.Gln356Ter)	Pathogenic
2147356	NM_018127.7(ELAC2):c.1727dup (p.Leu576fs)	Pathogenic
2169867	NM_018127.7(ELAC2):c.1535dup (p.Leu513fs)	Pathogenic
2177132	NM_018127.7(ELAC2):c.863_866del (p.Gly288fs)	Pathogenic
2196861	NM_018127.7(ELAC2):c.1245del (p.Met416fs)	Pathogenic
2577128	NM_018127.7(ELAC2):c.52C>T (p.Gln18Ter)	Pathogenic
2721694	NM_018127.7(ELAC2):c.865_866AG[2] (p.Glu290fs)	Pathogenic
2756840	NM_018127.7(ELAC2):c.299dup (p.Leu100fs)	Pathogenic
2988881	NM_018127.7(ELAC2):c.1214del (p.Cys405fs)	Pathogenic
3613950	NM_018127.7(ELAC2):c.406dup (p.Cys136fs)	Pathogenic
3616468	NM_018127.7(ELAC2):c.77_89del (p.Pro26fs)	Pathogenic
3628851	NM_018127.7(ELAC2):c.127C>T (p.Arg43Ter)	Pathogenic
3642387	NM_018127.7(ELAC2):c.1071G>A (p.Trp357Ter)	Pathogenic
3649547	NM_018127.7(ELAC2):c.526G>T (p.Glu176Ter)	Pathogenic
3656695	NM_018127.7(ELAC2):c.2278del (p.Met760fs)	Pathogenic
3661835	NM_018127.7(ELAC2):c.1802_1803insAACCA (p.His601fs)	Pathogenic
3672099	NM_018127.7(ELAC2):c.1423+1G>A	Pathogenic

SpliceAI

3361 predictions. Top by Δscore:

Variant	Effect	Δscore
17:12993041:CAGAC:C	acceptor_gain	1.0000
17:12993042:AGAC:A	acceptor_gain	1.0000
17:12993043:GAC:G	acceptor_gain	1.0000
17:12993043:GACC:G	acceptor_loss	1.0000
17:12993044:AC:A	acceptor_gain	1.0000
17:12993044:ACCT:A	acceptor_loss	1.0000
17:12993045:CC:C	acceptor_gain	1.0000
17:12993046:C:CA	acceptor_loss	1.0000
17:12993046:C:CC	acceptor_gain	1.0000
17:12993047:T:A	acceptor_loss	1.0000
17:12993054:C:CT	acceptor_gain	1.0000
17:12993056:CAA:C	acceptor_gain	1.0000
17:12993057:A:T	acceptor_gain	1.0000
17:12993058:A:AC	acceptor_gain	1.0000
17:12993058:A:C	acceptor_gain	1.0000
17:12993681:A:AC	donor_gain	1.0000
17:12993682:C:CC	donor_gain	1.0000
17:12993682:CAGA:C	donor_gain	1.0000
17:12993684:GAC:G	donor_loss	1.0000
17:12993686:CCTTC:C	donor_loss	1.0000
17:12993709:C:CA	donor_gain	1.0000
17:12993716:T:A	donor_gain	1.0000
17:12993827:TTGTG:T	acceptor_gain	1.0000
17:12993828:TGTG:T	acceptor_gain	1.0000
17:12993829:GTG:G	acceptor_gain	1.0000
17:12993830:TG:T	acceptor_gain	1.0000
17:12993832:C:CC	acceptor_gain	1.0000
17:12993838:G:C	acceptor_gain	1.0000
17:12993838:G:GC	acceptor_gain	1.0000
17:12994446:T:TA	donor_gain	1.0000

AlphaMissense

5420 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:12993770:G:C	H724D	0.999
17:12994427:G:C	H702Q	0.999
17:12994427:G:T	H702Q	0.999
17:12994429:G:C	H702D	0.999
17:12994474:C:G	A687P	0.999
17:12994476:T:A	E686V	0.999
17:12994795:G:C	D666E	0.999
17:12994795:G:T	D666E	0.999
17:12994796:T:A	D666V	0.999
17:12994796:T:G	D666A	0.999
17:12996555:G:C	H551D	0.999
17:12996556:A:C	D550E	0.999
17:12996556:A:T	D550E	0.999
17:12996557:T:A	D550V	0.999
17:12996557:T:C	D550G	0.999
17:12996557:T:G	D550A	0.999
17:12996558:C:G	D550H	0.999
17:12998432:A:C	S500R	0.999
17:12998432:A:T	S500R	0.999
17:12998434:T:G	S500R	0.999
17:12998442:C:G	R497P	0.999
17:12993762:G:C	S726R	0.998
17:12993762:G:T	S726R	0.998
17:12993764:T:G	S726R	0.998
17:12993768:G:C	H724Q	0.998
17:12993768:G:T	H724Q	0.998
17:12994475:T:A	E686D	0.998
17:12994475:T:G	E686D	0.998
17:12994796:T:C	D666G	0.998
17:12994797:C:G	D666H	0.998

dbSNP variants (sampled 300 via entrez): RS1000000156 (17:13017498 C>G), RS1000095240 (17:13012367 C>A), RS1000147076 (17:12993203 T>C), RS1000188093 (17:13000873 G>A), RS1000219292 (17:13000733 C>A,G,T), RS1000349460 (17:12995987 G>A), RS1000361851 (17:13002565 G>A), RS1000399007 (17:13006085 T>C), RS1000653888 (17:12997120 C>T), RS1000686298 (17:12996832 A>C,G), RS1000962857 (17:13001632 A>C), RS1001097389 (17:13011149 C>T), RS1001103018 (17:13015186 T>C), RS1001202690 (17:12992074 A>T), RS1001313161 (17:13014923 G>T)

Disease associations

OMIM: gene MIM:605367 | disease phenotypes: MIM:615440, MIM:614731, MIM:167000

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation defect type 17	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Mondo (5): combined oxidative phosphorylation defect type 17 (MONDO:0014190), prostate cancer, hereditary, 2 (MONDO:0013872), intellectual disability (MONDO:0001071), ovarian cancer (MONDO:0008170), microcephaly (MONDO:0001149)

Orphanet (4): Combined oxidative phosphorylation defect type 17 (Orphanet:369913), Familial prostate cancer (Orphanet:1331), Rare ovarian cancer (Orphanet:213500), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001522	Death in infancy
HP:0001635	Congestive heart failure
HP:0001639	Hypertrophic cardiomyopathy
HP:0003128	Lactic acidosis
HP:0003593	Infantile onset
HP:0003819	Death in childhood
HP:0008897	Postnatal growth retardation
HP:0011923	Decreased activity of mitochondrial complex I

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004750_11	Squamous cell lung carcinoma	4.000000e-06

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects reaction	2
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Tretinoin	decreases expression	2
Cadmium Chloride	decreases expression	2
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
urushiol	decreases expression	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	decreases expression	1
potassium chromate(VI)	increases expression	1
gossypol acetic acid	decreases expression	1
cupric chloride	affects expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
ProstaCaid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	affects methylation	1
Caffeine	decreases phosphorylation	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00001806	PHASE3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	PHASE3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	PHASE3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	PHASE3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	PHASE3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	PHASE3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	PHASE3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer