ENDOV

Summary

ENDOV (endonuclease V, HGNC:26640) is a protein-coding gene on chromosome 17q25.3, encoding Endonuclease V (Q8N8Q3). Endoribonuclease that specifically cleaves inosine-containing RNAs: cleaves RNA at the second phosphodiester bond 3’ to inosine.

Enables DNA binding activity; RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism; and single-stranded RNA binding activity. Predicted to be involved in DNA repair. Located in cytoplasmic stress granule and nucleolus.

Source: NCBI Gene 284131 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 80 total
• GTEx eGene: eQTL in 31 tissues, sQTL in 48 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.44 (unconstrained)
• MANE Select transcript: NM_173627
• Notable: 80 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26640
Approved symbol	ENDOV
Name	endonuclease V
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35220
Ensembl gene	ENSG00000173818
Ensembl biotype	protein_coding
OMIM	619821
Entrez	284131

Gene structure

Transcript identifiers

Ensembl transcripts: 62 — 42 protein_coding, 12 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 3 retained_intron

MANE Select: ENST00000518137

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 7, TSL 3: 9, TSL 4: 7, TSL 5: 3

ENST00000518137, ENST00000323854, ENST00000517295, ENST00000517795, ENST00000518644, ENST00000518901, ENST00000518907, ENST00000519117, ENST00000519331, ENST00000520118, ENST00000520136, ENST00000520284, ENST00000520367, ENST00000520484, ENST00000520537, ENST00000520565, ENST00000520910, ENST00000521330, ENST00000521565, ENST00000521634, ENST00000521830, ENST00000521847, ENST00000522200, ENST00000522577, ENST00000522751, ENST00000523165, ENST00000523228, ENST00000523828, ENST00000523999, ENST00000572886, ENST00000858819, ENST00000858820, ENST00000858821, ENST00000858822, ENST00000858823, ENST00000992798, ENST00000992799, ENST00000992800, ENST00000992801, ENST00000992802, ENST00000992803, ENST00000992804, ENST00000992805, ENST00000992806, ENST00001022772, ENST00001022773, ENST00001022774, ENST00001022775, ENST00001022776, ENST00001058102, ENST00001058103, ENST00001058104, ENST00001101860, ENST00001101861, ENST00001101862, ENST00001101863, ENST00001101864, ENST00001101865, ENST00001124251, ENST00001124252, ENST00001126731, ENST00001142052

RefSeq mRNA: 5 — MANE Select: NM_173627 NM_001164637, NM_001164638, NM_001352760, NM_001352761, NM_173627

CCDS: CCDS54172, CCDS54173, CCDS54174

Canonical transcript exons

ENST00000518137 — 10 exons

Exon	Start	End
ENSE00002112997	80415167	80415250
ENSE00002498626	80429773	80429831
ENSE00003463496	80425032	80425100
ENSE00003480396	80423520	80423632
ENSE00003481097	80422206	80422245
ENSE00003495191	80415650	80415821
ENSE00003595020	80421828	80421962
ENSE00003631980	80428596	80428660
ENSE00003789646	80425492	80425620
ENSE00004800131	80436133	80438086

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 96.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4211 / max 71.7681, expressed in 1747 samples.

Highest expression (Bgee): kidney epithelium, upper arm skin, parotid gland, uterine tube, cardiac muscle of right atrium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ENDOV is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 48 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 79 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	2.8e-71	+1.49	17:80418261:T:C
Skin Sun Exposed Lower leg	sqtl	5.2e-68	+2.19	17:80417033:G:T
Cells Cultured fibroblasts	sqtl	1.1e-66	+2.27	17:80417033:G:T
Lung	sqtl	2.8e-43	+2.11	17:80417033:G:T
Nerve Tibial	sqtl	6.5e-43	+1.99	17:80417033:G:T
Thyroid	sqtl	6.6e-40	-0.94	17:80418261:T:C
Skin Not Sun Exposed Suprapubic	sqtl	1.2e-39	+1.81	17:80417033:G:T
Adipose Subcutaneous	sqtl	7.9e-37	+1.77	17:80417033:G:T
Breast Mammary Tissue	sqtl	1.0e-32	+2.11	17:80403108:C:T
Muscle Skeletal	sqtl	2.2e-29	+1.46	17:80378776:G:T
Cells EBV-transformed lymphocytes	sqtl	1.1e-27	+2.22	17:80417033:G:T
Esophagus Gastroesophageal Junction	sqtl	7.2e-26	+2.17	17:80397633:T:G
Esophagus Muscularis	sqtl	2.3e-25	-0.86	17:80421934:G:A
Artery Tibial	sqtl	3.5e-24	-0.73	17:80418261:T:C
Esophagus Mucosa	sqtl	1.9e-23	+0.78	17:80418261:T:C
Colon Transverse	sqtl	2.2e-22	-0.87	17:80421934:G:A
Adipose Visceral Omentum	sqtl	1.2e-21	-0.78	17:80421934:G:A
Colon Sigmoid	sqtl	9.6e-19	-0.90	17:80418261:T:C
Stomach	sqtl	1.0e-18	-0.91	17:80421934:G:A
Spleen	sqtl	2.4e-15	-1.04	17:80421934:G:A

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
163245	3.6552	1640
163246	2.7146	1361
163247	0.0513	10

Top tissues by expression

showing 100 of 241 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	96.22	gold quality
upper arm skin	UBERON:0004263	95.32	gold quality
parotid gland	UBERON:0001831	93.84	silver quality
right uterine tube	UBERON:0001302	92.32	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.10	gold quality
left ventricle myocardium	UBERON:0006566	91.79	gold quality
lateral globus pallidus	UBERON:0002476	91.68	silver quality
vena cava	UBERON:0004087	91.18	silver quality
right hemisphere of cerebellum	UBERON:0014890	90.75	gold quality
cerebellar hemisphere	UBERON:0002245	90.49	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.37	gold quality
cerebellar cortex	UBERON:0002129	90.31	gold quality
cortical plate	UBERON:0005343	90.05	gold quality
left testis	UBERON:0004533	89.98	gold quality
metanephros cortex	UBERON:0010533	89.81	gold quality
cerebellum	UBERON:0002037	89.68	gold quality
right testis	UBERON:0004534	89.67	gold quality
adenohypophysis	UBERON:0002196	89.38	gold quality
epithelial cell of pancreas	CL:0000083	89.16	gold quality
nucleus accumbens	UBERON:0001882	89.06	gold quality
body of uterus	UBERON:0009853	89.04	gold quality
pituitary gland	UBERON:0000007	89.03	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.00	silver quality
cardia of stomach	UBERON:0001162	88.98	silver quality
endocervix	UBERON:0000458	88.54	gold quality
substantia nigra pars compacta	UBERON:0001965	88.40	silver quality
left ovary	UBERON:0002119	88.39	gold quality
left lobe of thyroid gland	UBERON:0001120	88.36	gold quality
skin of leg	UBERON:0001511	88.26	gold quality
cortex of kidney	UBERON:0001225	88.21	gold quality
right frontal lobe	UBERON:0002810	88.13	gold quality
ganglionic eminence	UBERON:0004023	88.13	gold quality
right ovary	UBERON:0002118	88.11	gold quality
gastrocnemius	UBERON:0001388	88.04	gold quality
pancreatic ductal cell	CL:0002079	88.03	silver quality
pericardium	UBERON:0002407	88.01	silver quality
testis	UBERON:0000473	87.92	gold quality
right lobe of thyroid gland	UBERON:0001119	87.87	gold quality
ectocervix	UBERON:0012249	87.71	gold quality
vastus lateralis	UBERON:0001379	87.69	gold quality
thyroid gland	UBERON:0002046	87.63	gold quality
apex of heart	UBERON:0002098	87.59	gold quality
pharyngeal mucosa	UBERON:0000355	87.57	silver quality
putamen	UBERON:0001874	87.56	gold quality
muscle of leg	UBERON:0001383	87.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.43	gold quality
hypothalamus	UBERON:0001898	87.34	gold quality
tibial nerve	UBERON:0001323	87.23	gold quality
amygdala	UBERON:0001876	87.21	gold quality
spleen	UBERON:0002106	87.15	gold quality
muscle tissue	UBERON:0002385	87.14	gold quality
anterior cingulate cortex	UBERON:0009835	87.13	gold quality
pylorus	UBERON:0001166	87.09	silver quality
skeletal muscle tissue	UBERON:0001134	87.02	gold quality
stromal cell of endometrium	CL:0002255	87.01	gold quality
uterine cervix	UBERON:0000002	86.95	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.93	gold quality
heart right ventricle	UBERON:0002080	86.92	silver quality
skin of abdomen	UBERON:0001416	86.90	gold quality
lower esophagus mucosa	UBERON:0035834	86.88	gold quality
saliva-secreting gland	UBERON:0001044	86.78	gold quality
metanephros	UBERON:0000081	86.71	gold quality
trachea	UBERON:0003126	86.70	silver quality
ventral tegmental area	UBERON:0002691	86.65	gold quality
caudate nucleus	UBERON:0001873	86.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.54	gold quality
fundus of stomach	UBERON:0001160	86.49	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.45	gold quality
deltoid	UBERON:0001476	86.44	silver quality
lower esophagus	UBERON:0013473	86.41	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.39	gold quality
prefrontal cortex	UBERON:0000451	86.33	gold quality
brain	UBERON:0000955	86.32	gold quality
body of stomach	UBERON:0001161	86.31	gold quality
left uterine tube	UBERON:0001303	86.23	gold quality
spinal cord	UBERON:0002240	86.22	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.22	gold quality
transverse colon	UBERON:0001157	86.09	gold quality
quadriceps femoris	UBERON:0001377	86.09	gold quality
midbrain	UBERON:0001891	86.07	gold quality
upper lobe of left lung	UBERON:0008952	86.07	gold quality
forebrain	UBERON:0001890	86.01	gold quality
substantia nigra	UBERON:0002038	86.01	gold quality
minor salivary gland	UBERON:0001830	85.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.94	gold quality
right lung	UBERON:0002167	85.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.84	gold quality
mucosa of stomach	UBERON:0001199	85.82	gold quality
pons	UBERON:0000988	85.77	silver quality
neocortex	UBERON:0001950	85.77	gold quality
frontal cortex	UBERON:0001870	85.72	gold quality
right lobe of liver	UBERON:0001114	85.66	gold quality
zone of skin	UBERON:0000014	85.55	gold quality
nipple	UBERON:0002030	85.55	gold quality
temporal lobe	UBERON:0001871	85.48	gold quality
small intestine	UBERON:0002108	85.40	gold quality
body of pancreas	UBERON:0001150	85.36	gold quality
stomach	UBERON:0000945	85.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.83
E-GEOD-100618	no	91.84

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Retina	tissue	24.4
Nucleus accumbens	tissue	23.1
Choroid plexus	tissue	19.2
Hippocampus	tissue	19.2
Postcentral gyrus	tissue	17.6
Locus coeruleus	tissue	16.7
Frontal cortex	tissue	13.3
Skin 1	tissue	12.8
Epididymis	tissue	11.0
Testis	tissue	10.9
Vagina	tissue	10.0
Salivary gland	tissue	9.8
Fallopian tube	tissue	9.6
Skeletal muscle	tissue	9.3
Pancreas	tissue	9.3
Pituitary gland	tissue	9.0
Prostate	tissue	7.9
Ovary	tissue	7.8
Endometrium 1	tissue	7.3
Kidney	tissue	7.2
Lung	tissue	7.1
Spleen	tissue	7.1
Caudate putamen	tissue	7.1
Liver	tissue	6.8
Breast	tissue	6.3
Stomach 1	tissue	6.2
Seminal vesicle	tissue	6.2
Gallbladder	tissue	6.0
Duodenum	tissue	5.9
Thyroid gland	tissue	5.7
Corpus callosum	tissue	5.6
Cervix	tissue	5.5
Parathyroid gland	tissue	5.5
Small intestine	tissue	5.4
Tongue	tissue	5.1
Spinal cord	tissue	5.1
Appendix	tissue	5.1
Lymph node	tissue	4.9
Esophagus	tissue	4.9
Thymus	tissue	4.9
Smooth muscle	tissue	4.7
Bone marrow	tissue	4.7
Adrenal gland	tissue	4.6
Adipose tissue	tissue	4.5
Substantia nigra	tissue	4.5
Rectum	tissue	4.4
Medulla oblongata	tissue	4.4
Periaqueductal gray	tissue	4.2
Hypothalamus	tissue	4.1
Colon	tissue	4.0
Placenta	tissue	4.0
Basal ganglia	tissue	3.9
Putamen	tissue	3.9
Midbrain	tissue	3.9
Thalamus	tissue	3.9
Superior colliculi	tissue	3.9
Ventral forebrain	tissue	3.9
Hippocampal formation	tissue	3.8
Pons	tissue	3.7
Urinary bladder	tissue	3.7

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Flocculonodular lobe (28.6), Vermis (26.5), Cerebellar cortex (26.2), Precentral gyrus (25.4), Basal amygdala (25.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ENDOV by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 54 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312

Functional genomics

gnomAD constraint: pLI 3.46e-14, LOEUF 1.44, missense Z -2.15 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000518137 — one region, missense o/e 1.17.

Literature-anchored findings (GeneRIF, showing 8)

• ENDOV is localized in the cytoplasm and nucleoli of human cells. (PMID:23139746)
• This previously unknown RNA incision activity may suggest a role for endonuclease V in normal RNA metabolism. (PMID:23912683)
• hEndoV controls the fate of inosine-containing RNA in humans. (PMID:23912718)
• ENDOV was significantly associated with schizophrenia. (PMID:25053281)
• Human EndoV appears inactive on DNA, but has been shown to incise various RNA substrates containing inosine. [review] (PMID:25824682)
• hEndoV is redistributed to stress granules as a strategy to create a local environment low in ATP to permit hEndoV activity. (PMID:27573237)
• Inosine-specific ribonuclease activity of natural variants of human endonuclease V (PMID:27800608)
• Base preference for inosine 3’-riboendonuclease activity of human endonuclease V: implications for cleavage of poly-A tails containing inosine. (PMID:38951658)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Endov	ENSMUSG00000039850
rattus_norvegicus	Endov	ENSRNOG00000003699

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2444688) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal skin morphology	1
increased circulating alkaline phosphatase level	1
decreased incidence of tumors by chemical induction	1
decreased circulating serum albumin level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Salmonella enterica subsp. enterica serovar Paratyphi B str. SPB7	A9N0L0	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Newport str. SL254	B4T100	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Heidelberg str. SL476	B4TCT7	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Paratyphi A str. AKU_12601	B5BJR7	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Agona str. SL483	B5F1I1	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Dublin str. CT_02021853	B5FQL3	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Enteritidis str. P125109	B5QYF3	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Gallinarum str. 287/91	B5RFI6	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Paratyphi C str. RKS4594	C0Q2T0	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Typhi	P68737	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2	P68738	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Choleraesuis str. SC-B67	Q57H57	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Paratyphi A str. ATCC 9150	Q5PKA2	100.0%	Diamond
Salmonella enterica subsp. arizonae serovar 62:z4,z23:-	A9MHD1	99.6%	Diamond
Salmonella enterica subsp. enterica serovar Schwarzengrund str. CVM19633	B4TQK8	99.6%	Diamond
Bacillus velezensis FZB42	A7Z9I5	85.3%	Diamond
Bacillus subtilis subsp. subtilis str. 168	P96724	85.3%	Diamond
Roseiflexus castenholzii DSM 13941	A7NSC5	84.2%	Diamond
Nostoc punctiforme PCC 73102	B2IWL4	80.8%	Diamond
Serratia proteamaculans 568	A8G8F8	79.4%	Diamond
Sodalis glossinidius str. ‘morsitans’	Q2NWR1	77.7%	Diamond
Pyrococcus horikoshii OT3	O58394	73.4%	Diamond
Pyrococcus furiosus DSM 3638	Q8U263	67.8%	Diamond
Azotobacter vinelandii DJ	C1DQ77	64.4%	Diamond
Natronomonas pharaonis DSM 2160	Q3IT64	58.2%	Diamond
Alkalilimnicola ehrlichii MLHE-1	Q0A5M1	56.4%	Diamond
Thermoplasma volcanium GSS1	Q97AL5	54.3%	Diamond
Aquifex aeolicus VF5	O66824	50.0%	Diamond
Schizosaccharomyces pombe 972h-	Q10348	44.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR4730	ncRNA	100616359
SLC26A11	protein-coding	284129
NPTX1	protein-coding	4884
RNF213	protein-coding	57674
SGSH	protein-coding	6448
CARD14	protein-coding	79092
RNF213-AS1	ncRNA	100294362
RPTOR	protein-coding	57521
EIF4A3	protein-coding	9775

Protein

Protein identifiers

Endonuclease V — Q8N8Q3 (reviewed: Q8N8Q3)

Alternative names: Inosine-specific endoribonuclease

All UniProt accessions (15): A0A0G2JLD4, E5RFW0, E5RGZ9, E5RHX4, E5RII5, E5RJ92, Q8N8Q3, H0YAY5, H0YBX8, H0YBZ5, I3L0L4, I3L1V3, I3L485, I3L4M6, I3L4V7

UniProt curated annotations — full annotation on UniProt →

Function. Endoribonuclease that specifically cleaves inosine-containing RNAs: cleaves RNA at the second phosphodiester bond 3’ to inosine. Active against both single-stranded and double-stranded RNAs. Has strong preference for single-stranded RNAs (ssRNAs) toward double-stranded RNAs (dsRNAs). Cleaves mRNAs and tRNAs containing inosine. Also able to cleave structure-specific dsRNA substrates containing the specific sites 5’-IIUI-3’ and 5’-UIUU-3’. Inosine is present in a number of RNAs following editing; the function of inosine-specific endoribonuclease is still unclear: it could either play a regulatory role in edited RNAs, or be involved in antiviral response by removing the hyperedited long viral dsRNA genome that has undergone A-to-I editing. Binds branched DNA structures. Endoribonuclease that specifically cleaves inosine-containing RNAs: cleaves RNA at the second phosphodiester bond 3’ to inosine. Active against both single-stranded and double-stranded RNAs. Cleaves tRNAs containing inosine. Endoribonuclease that specifically cleaves inosine-containing RNAs: cleaves RNA at the second phosphodiester bond 3’ to inosine. Active against both single-stranded and double-stranded RNAs. Cleaves tRNAs containing inosine.

Subunit / interactions. Monomer. Interacts with PABPC1; the interaction is RNA-dependent and stimulates ENDOV activity.

Subcellular location. Cytoplasm. Nucleus. Nucleolus. Stress granule Cytoplasm. Stress granule.

Activity regulation. Inhibited by normal intracellular concentrations of ATP.

Similarity. Belongs to the endonuclease V family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q8N8Q3-1	1, hENDOV 282	yes
Q8N8Q3-2	2
Q8N8Q3-3	3
Q8N8Q3-4	4
Q8N8Q3-5	5
Q8N8Q3-6	6, hENDOV 308
Q8N8Q3-7	7, hENDOV 309

RefSeq proteins (5): NP_001158109, NP_001158110, NP_001339689, NP_001339690, NP_775898* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007581	Endonuclease-V	Family

Pfam: PF04493

Enzyme classification (BRENDA)

• EC 3.1.21.7 — deoxyribonuclease V (BRENDA: 17 organisms, 91 substrates, 22 inhibitors, 4 Km, 8 kcat entries)
• EC 3.1.27.8 — Ribonuclease V (BRENDA: 2 organisms, 7 substrates, 0 inhibitors, 1 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
49-MER OLIGONUCLEOTIDE	0.003–0.024	4
POLY(A)	0.0357	1
18-MER RNA OLIGONUCLEOTIDE CONTAINING INOSINE	—	0
30-MER DNA/RNA CONTAINING INOSINE HYBRID	—	0
ACUGGACA[RI][RI]U[RI]CUCCGAGG	—	0

UniProt features (50 total): mutagenesis site 15, strand 10, helix 8, sequence variant 5, splice variant 5, binding site 2, chain 1, region of interest 1, sequence conflict 1, turn 1, site 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
6OZE	Crystal structure of the catalytic domain of human Endonuclease V …	X-RAY DIFFRACTION	1.5
4NSP	Crystal structure of human ENDOV	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N8Q3-F1	90.90	0.83

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

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)

Position	Role
91	interaction with target rna

Ligand- & substrate-binding residues (2)

Position	Role
52	Mg(2+)
126	Mg(2+)

Mutagenesis-validated functional residues (15)

Position	Phenotype
35–40	does not gain activity against single- or double-stranded dna.
52	abolishes ribonuclease activity.
57–60	does not gain activity against single- or double-stranded dna.
90–93	abolishes ability to bind branched dna and rna.
91	abolishes ribonuclease activity without affecting ability to bind branched dna.
100	abolishes ribonuclease activity.
115–119	does not gain activity against single- or double-stranded dna.
161–166	does not gain activity against single- or double-stranded dna.
171	no effect on subcellular location or activity; when associated with a-174.
174	no effect on subcellular location or activity; when associated with a-171.
225	no significant effect on activity.
226	no significant effect on activity.
227	68% decrease in activity.
228	46% decrease in activity.
248–249	abolishes ability to bind branched dna and rna.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 94 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, KAUFFMANN_DNA_REPAIR_GENES, GOMF_RNA_ENDONUCLEASE_ACTIVITY, GOBP_DNA_DAMAGE_RESPONSE, GOMF_DNA_ENDONUCLEASE_ACTIVITY, GOCC_CYTOPLASMIC_STRESS_GRANULE, GOCC_RIBONUCLEOPROTEIN_GRANULE, GOCC_NUCLEOLUS, GOBP_DNA_METABOLIC_PROCESS, SCGGAAGY_ELK1_02, GOMF_DNA_ENDONUCLEASE_ACTIVITY_PRODUCING_5_PHOSPHOMONOESTERS, MGGAAGTG_GABP_B, GOMF_MAGNESIUM_ION_BINDING

GO Biological Process (1): DNA repair (GO:0006281)

GO Molecular Function (12): magnesium ion binding (GO:0000287), DNA binding (GO:0003677), single-stranded RNA binding (GO:0003727), DNA endonuclease activity, producing 5’-phosphomonoesters (GO:0016888), RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism (GO:0016891), RNA binding (GO:0003723), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on ester bonds (GO:0016788), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleolus (GO:0005730), cytoplasm (GO:0005737), cytoplasmic stress granule (GO:0010494)

GO top-level categories

19 GO namespaces:

Category	Terms
nucleic acid binding	2
hydrolase activity, acting on ester bonds	2
DNA metabolic process	1
DNA damage response	1
metal ion binding	1
RNA binding	1
DNA endonuclease activity	1
RNA endonuclease activity	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
binding	1
catalytic activity	1
hydrolase activity	1
cation binding	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasmic ribonucleoprotein granule	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
cytoplasm	CC	direct assay
cytoplasmic stress granule	CC	direct assay
nucleolus	CC	direct assay
DNA binding	MF	direct assay
RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism	MF	direct assay
single-stranded RNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,238 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENDOV	ITPA	Q9BY32	602
ENDOV	HENMT1	Q5T8I9	551
ENDOV	AGO3	Q9H9G7	551
ENDOV	AGO4	Q9HCK5	551
ENDOV	MPG	P29372	550
ENDOV	TARBP2	Q15633	545
ENDOV	GEMIN5	Q8TEQ6	510
ENDOV	GEMIN6	Q8WXD5	498
ENDOV	NEIL1	Q96FI4	493
ENDOV	ZFP36	P26651	490
ENDOV	GEMIN2	O14893	487
ENDOV	EXO5	Q9H790	482
ENDOV	ZBTB39	O15060	479
ENDOV	ADAT3	Q96EY9	477
ENDOV	PPP1R27	Q86WC6	472

IntAct

Human interaction partners of ENDOV in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
PDCL	association	0.350	1
VWA8	association	0.350	1
NELFCD	physical association	0.000	1
PRPSAP2	physical association	0.000	1

BioGRID (44 interactions; top human partners by supporting records): ANKRD40 (Affinity Capture-MS; 3 records), APAF1 (Affinity Capture-MS; 3 records), PDCL (Affinity Capture-MS; 3 records), RNF31 (Affinity Capture-MS; 3 records), SEPHS2 (Affinity Capture-MS; 3 records), VWA8 (Affinity Capture-MS; 3 records), TSC22D3 (Affinity Capture-MS; 2 records), AMBRA1 (Proximity Label-MS), APEX1 (Affinity Capture-RNA), BBS2 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), DCAF15 (Proximity Label-MS), DCAF7 (Proximity Label-MS), DET1 (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for ENDOV: 80 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	1
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 1,461):

Position(s)	Effect	Δscore	Sites
17:80423633–80423634	donor_loss	1.0000	2
17:80425101–80425102	donor_loss	1.0000	5
17:80425621–80425622	donor_loss	1.0000	5
17:80415412	donor_gain	0.9900
17:80417728	acceptor_gain	0.9900
17:80423518–80423519	acceptor_loss	0.9900	6
17:80423633–80423634	donor_loss	0.9900	2
17:80425024	acceptor_gain	0.9900
17:80425030–80425031	acceptor_loss	0.9900	6
17:80436104	acceptor_gain	0.9900

AlphaMissense

642 missense substitutions predicted likely pathogenic (of 1,788 scored), across 164 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D126	8	0.980	0.995
D52	8	0.975	0.991
D240	8	0.963	0.987
H132	8	0.945	0.989
F98	8	0.921	0.992
H213	8	0.876	0.962
F183	8	0.862	0.972
H141	8	0.858	0.983
E100	7	0.974	0.986
W36	7	0.971	0.992
F95	7	0.964	0.989
F55	7	0.933	0.992
K155	7	0.932	0.995
W17	7	0.912	0.971
F136	7	0.905	0.978
F230	7	0.900	0.986
N128	7	0.881	0.984
E234	7	0.868	0.918
F72	7	0.842	0.927
D32	7	0.840	0.901

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Thyroid Carcinoma (TCGA)	unfavorable	7.31e-06
Prostate Adenocarcinoma (TCGA)	unfavorable	0.000446

Disease associations

OMIM: gene MIM:619821 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST009204_11	Total intracranial volume	9e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004886	intracranial volume measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
ferrous chloride	decreases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Catechin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Methapyrilene	decreases methylation	1
Phthalic Acids	increases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Particulate Matter	increases expression	1

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9E9	Ubigene HEK293 ENDOV KO	Transformed cell line	Female
CVCL_SM05	HAP1 ENDOV (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.