ELAC1

Summary

ELAC1 (elaC ribonuclease Z 1, HGNC:14197) is a protein-coding gene on chromosome 18q21.2, encoding Zinc phosphodiesterase ELAC protein 1 (Q9H777). Zinc phosphodiesterase, which displays some tRNA 3’-processing endonuclease activity.

Enables tRNA-specific ribonuclease activity. Involved in rescue of stalled ribosome and tRNA 3’-end processing. Located in cytosol and nucleoplasm.

Source: NCBI Gene 55520 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_018696

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14197
Approved symbol	ELAC1
Name	elaC ribonuclease Z 1
Location	18q21.2
Locus type	gene with protein product
Status	Approved
Aliases	D29
Ensembl gene	ENSG00000141642
Ensembl biotype	protein_coding
OMIM	608079
Entrez	55520

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000269466, ENST00000586966, ENST00000588577, ENST00000591429, ENST00000858935, ENST00000858936, ENST00000858937, ENST00000858938, ENST00000858939, ENST00000858940, ENST00000858941, ENST00000917712, ENST00000961942, ENST00000961943, ENST00000961944

RefSeq mRNA: 1 — MANE Select: NM_018696 NM_018696

CCDS: CCDS11949

Canonical transcript exons

ENST00000269466 — 4 exons

Exon	Start	End
ENSE00000950200	50984096	50984563
ENSE00000950201	50986619	50988121
ENSE00001216917	50968040	50968114
ENSE00003614593	50974397	50974561

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 83.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.7839 / max 53.0413, expressed in 1788 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170267	9.7839	1788

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	83.01	gold quality
calcaneal tendon	UBERON:0003701	81.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.76	gold quality
right adrenal gland	UBERON:0001233	80.67	gold quality
right lobe of thyroid gland	UBERON:0001119	80.51	gold quality
tendon	UBERON:0000043	80.42	gold quality
body of pancreas	UBERON:0001150	80.39	gold quality
left adrenal gland	UBERON:0001234	80.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.05	gold quality
right adrenal gland cortex	UBERON:0035827	79.99	gold quality
left adrenal gland cortex	UBERON:0035825	79.77	gold quality
right lobe of liver	UBERON:0001114	79.62	gold quality
pancreas	UBERON:0001264	79.52	gold quality
mucosa of transverse colon	UBERON:0004991	79.51	gold quality
tendon of biceps brachii	UBERON:0008188	79.32	gold quality
adenohypophysis	UBERON:0002196	79.29	gold quality
left lobe of thyroid gland	UBERON:0001120	79.22	gold quality
rectum	UBERON:0001052	78.68	gold quality
thyroid gland	UBERON:0002046	78.61	gold quality
monocyte	CL:0000576	78.44	gold quality
leukocyte	CL:0000738	78.35	gold quality
mononuclear cell	CL:0000842	78.18	gold quality
adrenal gland	UBERON:0002369	78.16	gold quality
adrenal cortex	UBERON:0001235	78.12	gold quality
granulocyte	CL:0000094	77.96	gold quality
pituitary gland	UBERON:0000007	77.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.62	gold quality
body of stomach	UBERON:0001161	76.38	gold quality
apex of heart	UBERON:0002098	76.05	gold quality
ventricular zone	UBERON:0003053	76.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting ELAC1, 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-497-5P	99.92	71.83	2674
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6809-3P	99.91	71.45	3814
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-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378B	98.43	65.36	573
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548
HSA-MIR-378E	98.43	65.99	551
HSA-MIR-378F	98.43	65.66	554
HSA-MIR-378H	98.43	66.16	545
HSA-MIR-378I	98.43	66.10	548
HSA-MIR-5589-5P	98.34	64.82	1148

Literature-anchored findings (GeneRIF, showing 4)

• Human tRNase ZS gene expression appears to be post-transcriptionally regulated. (PMID:18573253)
• ELAC1 Repairs tRNAs Cleaved during Ribosome-Associated Quality Control. (PMID:32075755)
• Transcription from the proximal promoter of ELAC1, a gene for tRNA repair, is upregulated by interferons. (PMID:34808499)
• Genes for tRNA recycling are upregulated in response to infection with Theiler’s mouse encephalitis virus. (PMID:34864548)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	elac1	ENSDARG00000045095
mus_musculus	Elac1	ENSMUSG00000036941
rattus_norvegicus	Elac1	ENSRNOG00000000113

Paralogs (1): ELAC2 (ENSG00000006744)

Protein

Protein identifiers

Zinc phosphodiesterase ELAC protein 1 — Q9H777 (reviewed: Q9H777)

Alternative names: Deleted in Ma29, ElaC homolog protein 1, Ribonuclease Z 1, tRNA 3 endonuclease 1, tRNase Z 1

All UniProt accessions (3): Q9H777, K7EIJ1, K7EPH7

UniProt curated annotations — full annotation on UniProt →

Function. Zinc phosphodiesterase, which displays some tRNA 3’-processing endonuclease activity. Specifically involved in tRNA repair: acts downstream of the ribosome-associated quality control (RQC) pathway by removing a 2’,3’-cyclic phosphate from tRNAs following cleavage by ANKZF1. tRNAs are then processed by TRNT1.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Tissue specificity. Widely expressed. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Cofactor. Binds 2 Zn(2+) ions.

Similarity. Belongs to the RNase Z family.

RefSeq proteins (1): NP_061166* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013471	RNase_Z/BN	Family
IPR036866	RibonucZ/Hydroxyglut_hydro	Homologous_superfamily

Pfam: 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 (45 total): strand 18, helix 10, binding site 8, turn 3, sequence conflict 2, chain 1, active site 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3ZWF	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H777-F1	91.90	0.79

Functional residue map

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

Catalytic / active sites (1): 66 (proton acceptor)

Ligand- & substrate-binding residues (8): 62; 64; 66; 67; 182; 253; 253; 313

Mutagenesis-validated functional residues (1):

Position	Phenotype
64	abolsihed trnase activity and ability to repair trnas downstream of ankzf1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 135 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, MODULE_255, GOMF_NUCLEASE_ACTIVITY, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MODULE_317, GOBP_TRANSLATION, GOMF_RNA_ENDONUCLEASE_ACTIVITY, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_TRANSLATIONAL_ELONGATION

GO Biological Process (4): tRNA 3’-end processing (GO:0042780), rescue of stalled cytosolic ribosome (GO:0072344), tRNA 3’-terminal CCA addition (GO:0001680), tRNA processing (GO:0008033)

GO Molecular Function (7): 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), RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism (GO:0016891)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
tRNA 3’-end processing	2
tRNA processing	1
RNA 3’-end processing	1
cytoplasmic translational elongation	1
ribosome disassembly	1
CCA tRNA nucleotidyltransferase activity	1
CC tRNA cytidylyltransferase activity	1
ATP:3’-cytidine-cytidine-tRNA adenylyltransferase activity	1
RNA processing	1
tRNA metabolic process	1
RNA nuclease 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
RNA endonuclease activity	1
hydrolase activity, acting on ester bonds	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELAC1	TRNT1	Q96Q11	640
ELAC1	INTS11	Q5TA45	607
ELAC1	INTS9	Q9NV88	593
ELAC1	MBLAC1	A4D2B0	531
ELAC1	DCLRE1A	Q6PJP8	519
ELAC1	REXO2	Q9Y3B8	492
ELAC1	CPSF3	Q9UKF6	478
ELAC1	LACTB2	Q53H82	476
ELAC1	SUPV3L1	Q8IYB8	469
ELAC1	CPSF2	Q9P2I0	443
ELAC1	MEX3C	Q5U5Q3	441
ELAC1	DCLRE1B	Q9H816	412
ELAC1	HAGH	Q16775	410
ELAC1	EXOSC10	Q01780	382
ELAC1	GTPBP3	Q969Y2	382

IntAct

0 interactions, top by confidence:

BioGRID (5): ELAC1 (Biochemical Activity), ELAC1 (Protein-RNA), ELAC1 (Protein-RNA), ELAC1 (Positive Genetic), ELAC1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1L9WLF1, A0A4P8DJU1, A0A7R7ZLL0, A2C7W3, A2QX23, A6QLU1, A7DZP8, A7SMW7, B4F6K2, G3KLH5, M1WCF7, O24495, O24496, O35952, O94250, P13995, P18155, P35571, Q05584, Q0P5C2, Q12320, Q16775, Q26547, Q28333, Q2TAP9, Q3B7M2, Q3T094, Q4R6C1, Q4VK78, Q4W945, Q58CN9, Q5ZI23, Q5ZLY2, Q64521, Q6NYF0, Q6P963, Q769K2, Q7V6G8, Q8K009, Q8LDW8

Diamond homologs: A0A217ER65, A0A2W1NDJ7, A0A345MJY6, A0A4Y6UQ63, A0A516KNH9, A0A848M4Z0, A0A8G1LR08, A0AK82, A0PTY0, A0Q1D1, A1KL99, A1R0H8, A1UIW4, A2BY56, A2C4C2, A3Q2B8, A4T2G4, A5MZX7, A5VJA0, A6LU82, A6UUY8, A6VFJ7, A7GSG2, A8ABB4, A8MGK0, A9A3X2, A9KSU3, B0JGG3, B2G6S0, B2HMC3, B2S197, B2S457, B2TN28, B2V377, B5RMU7, B5RQ92, B6YT50, B7IWQ5, B7J0K1, B7K1N1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

786 predictions. Top by Δscore:

Variant	Effect	Δscore
18:50974395:A:AG	acceptor_gain	1.0000
18:50974395:AG:A	acceptor_gain	1.0000
18:50974396:G:GG	acceptor_gain	1.0000
18:50974396:GG:G	acceptor_gain	1.0000
18:50984396:G:GT	donor_gain	1.0000
18:50968712:C:G	donor_gain	0.9900
18:50974390:GTTGC:G	acceptor_loss	0.9900
18:50974391:TTGCA:T	acceptor_loss	0.9900
18:50974392:TGCA:T	acceptor_loss	0.9900
18:50974392:TGCAG:T	acceptor_loss	0.9900
18:50974393:GCA:G	acceptor_loss	0.9900
18:50974393:GCAG:G	acceptor_loss	0.9900
18:50974394:CA:C	acceptor_loss	0.9900
18:50974394:CAGG:C	acceptor_loss	0.9900
18:50974395:A:AC	acceptor_loss	0.9900
18:50974395:AGGG:A	acceptor_loss	0.9900
18:50974395:AGGGT:A	acceptor_gain	0.9900
18:50974396:G:GA	acceptor_loss	0.9900
18:50974396:GGGTG:G	acceptor_gain	0.9900
18:50974558:GCAG:G	donor_gain	0.9900
18:50974559:CAG:C	donor_loss	0.9900
18:50974560:AG:A	donor_loss	0.9900
18:50974560:AGG:A	donor_loss	0.9900
18:50974561:GG:G	donor_loss	0.9900
18:50974561:GGTT:G	donor_loss	0.9900
18:50974562:G:T	donor_loss	0.9900
18:50974562:GTT:G	donor_loss	0.9900
18:50974563:T:G	donor_loss	0.9900
18:50986618:GGT:G	acceptor_gain	0.9900
18:50987059:GTGA:G	donor_gain	0.9900

AlphaMissense

2375 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:50984135:A:T	D66V	0.999
18:50986751:A:T	D253V	0.999
18:50986817:A:T	E275V	0.999
18:50987050:G:C	D353H	0.999
18:50974430:G:A	G9E	0.998
18:50974515:T:G	C37W	0.998
18:50984135:A:C	D66A	0.998
18:50984136:C:A	D66E	0.998
18:50984136:C:G	D66E	0.998
18:50984222:G:A	G95D	0.998
18:50984482:C:G	H182D	0.998
18:50984552:T:A	L205H	0.998
18:50986819:G:C	A276P	0.998
18:50986864:C:G	H291D	0.998
18:50986936:A:C	S315R	0.998
18:50986938:T:A	S315R	0.998
18:50986938:T:G	S315R	0.998
18:50974429:G:T	G9W	0.997
18:50974513:T:C	C37R	0.997
18:50974514:G:A	C37Y	0.997
18:50974516:G:T	G38W	0.997
18:50984135:A:G	D66G	0.997
18:50984147:G:A	G70D	0.997
18:50984159:T:C	L74P	0.997
18:50986930:C:G	H313D	0.997
18:50986943:G:C	R317T	0.997
18:50986943:G:T	R317M	0.997
18:50986944:G:C	R317S	0.997
18:50986944:G:T	R317S	0.997
18:50974429:G:A	G9R	0.996

dbSNP variants (sampled 300 via entrez): RS1000197488 (18:50978762 G>C), RS1000481110 (18:50985368 C>T), RS1000833459 (18:50966706 C>A), RS1001154473 (18:50972625 G>A,C), RS1001211418 (18:50979824 T>G), RS1001229277 (18:50973362 G>A), RS1001243486 (18:50977735 C>G,T), RS1001473941 (18:50983231 C>T), RS1001614613 (18:50966652 C>G), RS1001909803 (18:50972442 C>T), RS1002247991 (18:50977020 C>A,T), RS1002473521 (18:50967340 T>C), RS1002583314 (18:50975438 G>A), RS1002598545 (18:50983523 A>G), RS1002634225 (18:50975765 C>G)

Disease associations

OMIM: gene MIM:608079 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001538_12	Immune reponse to smallpox (secreted IFN-alpha)	2.000000e-07
GCST002758_2	Oligoclonal band status in multiple sclerosis	8.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0005206	oligoclonal band measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
Air Pollutants	affects expression, increases abundance, increases expression	2
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases expression	1
cylindrospermopsin	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lead	affects expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1
Thimerosal	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SL82	HAP1 ELAC1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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