ENDOD1

Summary

ENDOD1 (endonuclease domain containing 1, HGNC:29129) is a protein-coding gene on chromosome 11q21, encoding Endonuclease domain-containing 1 protein (O94919). May act as a DNase and a RNase.

Predicted to enable endonuclease activity; metal ion binding activity; and nucleic acid binding activity. Predicted to be involved in innate immune response. Located in extracellular exosome and membrane.

Source: NCBI Gene 23052 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 89 total
• Druggable target: yes
• MANE Select transcript: NM_015036

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29129
Approved symbol	ENDOD1
Name	endonuclease domain containing 1
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0830
Ensembl gene	ENSG00000149218
Ensembl biotype	protein_coding
OMIM	619568
Entrez	23052

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000278505, ENST00000878168

RefSeq mRNA: 1 — MANE Select: NM_015036 NM_015036

CCDS: CCDS41699

Canonical transcript exons

ENST00000278505 — 2 exons

Exon	Start	End
ENSE00000989412	95089846	95090227
ENSE00001099123	95128377	95132645

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 97.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.8128 / max 536.2809, expressed in 1778 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116305	32.3666	1776
116306	0.7036	451
116304	0.4828	198
116307	0.1524	46
116302	0.0596	28
116303	0.0479	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	97.32	gold quality
corpus callosum	UBERON:0002336	97.18	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.05	gold quality
inferior vagus X ganglion	UBERON:0005363	96.63	gold quality
pons	UBERON:0000988	96.56	gold quality
trigeminal ganglion	UBERON:0001675	96.44	gold quality
right coronary artery	UBERON:0001625	95.57	gold quality
subthalamic nucleus	UBERON:0001906	95.37	gold quality
popliteal artery	UBERON:0002250	95.07	gold quality
tibial artery	UBERON:0007610	95.07	gold quality
calcaneal tendon	UBERON:0003701	94.94	gold quality
superior vestibular nucleus	UBERON:0007227	94.94	gold quality
biceps brachii	UBERON:0001507	94.88	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.82	gold quality
inferior olivary complex	UBERON:0002127	94.70	gold quality
medulla oblongata	UBERON:0001896	94.35	gold quality
left coronary artery	UBERON:0001626	94.31	gold quality
coronary artery	UBERON:0001621	94.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.19	gold quality
medial globus pallidus	UBERON:0002477	94.16	gold quality
spinal cord	UBERON:0002240	94.11	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.09	gold quality
globus pallidus	UBERON:0001875	94.07	gold quality
aorta	UBERON:0000947	93.72	gold quality
tibial nerve	UBERON:0001323	93.71	gold quality
rectum	UBERON:0001052	93.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.42	gold quality
colonic mucosa	UBERON:0000317	93.41	gold quality
hair follicle	UBERON:0002073	93.36	gold quality
cranial nerve II	UBERON:0000941	93.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

134 targeting ENDOD1, 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-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-146A-5P	99.96	68.93	988

Literature-anchored findings (GeneRIF, showing 1)

• Overexpression of ENDOD1 suppressed cell proliferation, induced G0/G1 cell cycle arrest and inhibited cell migration and invasion. (PMID:28532481)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-165i18.2	ENSDARG00000077239
danio_rerio	zgc:171534	ENSDARG00000105265
mus_musculus	Endod1	ENSMUSG00000037419
rattus_norvegicus	Endod1	ENSRNOG00000024757

Protein

Protein identifiers

Endonuclease domain-containing 1 protein — O94919 (reviewed: O94919)

All UniProt accessions (1): O94919

UniProt curated annotations — full annotation on UniProt →

Function. May act as a DNase and a RNase. Plays a role in the modulation of innate immune signaling through the cGAS-STING pathway by interacting with RNF26.

Subunit / interactions. Interacts with RNF26; this interaction is important to modulate innate immune signaling through the cGAS-STING pathway.

Subcellular location. Secreted.

Similarity. Belongs to the DNA/RNA non-specific endonuclease family.

RefSeq proteins (1): NP_055851* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001604	Endo_G_ENPP1-like_dom	Domain
IPR020821	ENPP1-3/EXOG-like_nuc-like	Domain
IPR039015	ENDOD1	Family
IPR044925	His-Me_finger_sf	Homologous_superfamily
IPR044929	DNA/RNA_non-sp_Endonuclease_sf	Homologous_superfamily

Pfam: PF01223

UniProt features (9 total): sequence variant 2, sequence conflict 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94919-F1	81.44	0.46

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 (1): 407

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation

MSigDB gene sets: 256 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOMF_ENDONUCLEASE_ACTIVITY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOMF_NUCLEASE_ACTIVITY, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, WEI_MYCN_TARGETS_WITH_E_BOX, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM

GO Biological Process (2): innate immune response (GO:0045087), immune system process (GO:0002376)

GO Molecular Function (6): nucleic acid binding (GO:0003676), endonuclease activity (GO:0004519), hydrolase activity (GO:0016787), metal ion binding (GO:0046872), nuclease activity (GO:0004518), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), cytosol (GO:0005829), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
immune response	1
defense response to symbiont	1
biological_process	1
nuclease activity	1
catalytic activity	1
cation binding	1
catalytic activity, acting on a nucleic acid	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

1608 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENDOD1	TMEM33	P57088	706
ENDOD1	TMEM43	Q9BTV4	706
ENDOD1	RNF26	Q9BY78	658
ENDOD1	TMED1	Q13445	550
ENDOD1	C2CD2	Q9Y426	488
ENDOD1	FAM8A1	Q9UBU6	485
ENDOD1	TM2D1	Q9BX74	475
ENDOD1	LMAN2	Q12907	428
ENDOD1	UAP1	Q16222	418
ENDOD1	CRYZL1	O95825	403
ENDOD1	FBXO4	Q9UKT5	395
ENDOD1	ECHDC1	Q9NTX5	384
ENDOD1	TRDMT1	O14717	383
ENDOD1	UBTD2	Q8WUN7	381
ENDOD1	ABHD1	Q96SE0	377

IntAct

127 interactions, top by confidence:

A	B	Type	Score
COG7	ILVBL	psi-mi:“MI:0914”(association)	0.640
BZW2	ENDOD1	psi-mi:“MI:0914”(association)	0.640
LYPD3	SCAMP1	psi-mi:“MI:0914”(association)	0.640
ENDOD1	VSNL1	psi-mi:“MI:0915”(physical association)	0.560
SLC19A2	ENDOD1	psi-mi:“MI:0915”(physical association)	0.560
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
BZW2	SLC27A2	psi-mi:“MI:0914”(association)	0.530
SMPD3	ENDOD1	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
REEP1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
SSMEM1	ENDOD1	psi-mi:“MI:0914”(association)	0.530
TMEM43	ENDOD1	psi-mi:“MI:0914”(association)	0.530
AGPAT3	ENDOD1	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
RFFL	TUSC2	psi-mi:“MI:0914”(association)	0.530
SLC34A2	LGALS8	psi-mi:“MI:0914”(association)	0.530
FLVCR1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
STOM	EI24	psi-mi:“MI:0914”(association)	0.510
env	PGRMC1	psi-mi:“MI:0914”(association)	0.460
Dicer1	ENDOD1	psi-mi:“MI:0914”(association)	0.350
Uso1	SLC30A6	psi-mi:“MI:0914”(association)	0.350
KIF21A	NCOA4	psi-mi:“MI:0914”(association)	0.350

BioGRID (138): ENDOD1 (Affinity Capture-RNA), ENDOD1 (Affinity Capture-RNA), ENDOD1 (Affinity Capture-RNA), ENDOD1 (Affinity Capture-RNA), ENDOD1 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M9PDM1, A2VDN0, E1B9E5, F1MWM0, F1QYC4, O09051, O35600, O70418, O88393, O94919, O95477, P0DP43, P26342, P35054, P41233, P41234, P49932, P58239, P70668, P78363, Q03167, Q16661, Q1KLX0, Q1KLX2, Q1KLX5, Q1KLY5, Q1KLY7, Q1KLY8, Q20CR4, Q3TT99, Q4G0G5, Q4TVR5, Q4VSN4, Q4VSN5, Q5ZKZ4, Q6W3E5, Q6XUX1, Q6XUX2, Q6XUX3, Q8C522

Diamond homologs: O94919, Q8C522

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 147 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
Neutrophil degranulation	15	4.2×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

338 predictions. Top by Δscore:

Variant	Effect	Δscore
11:95090225:CAGGT:C	donor_loss	1.0000
11:95090226:AGG:A	donor_loss	1.0000
11:95090227:GGTA:G	donor_loss	1.0000
11:95090229:T:A	donor_loss	1.0000
11:95090224:GCAG:G	donor_gain	0.9900
11:95090228:G:GG	donor_gain	0.9900
11:95128371:TTGCA:T	acceptor_loss	0.9900
11:95128372:TGCA:T	acceptor_loss	0.9900
11:95128373:GCA:G	acceptor_loss	0.9900
11:95128374:CAG:C	acceptor_loss	0.9900
11:95128375:A:AG	acceptor_gain	0.9900
11:95128375:A:T	acceptor_loss	0.9900
11:95128375:AGATC:A	acceptor_gain	0.9900
11:95128376:G:GA	acceptor_loss	0.9900
11:95128376:G:GG	acceptor_gain	0.9900
11:95128376:GATC:G	acceptor_gain	0.9900
11:95128376:GATCG:G	acceptor_gain	0.9900
11:95127340:G:GT	donor_gain	0.9600
11:95129044:G:T	donor_gain	0.9600
11:95128376:GA:G	acceptor_gain	0.9400
11:95128376:GAT:G	acceptor_gain	0.9400
11:95093962:G:GT	donor_gain	0.9300
11:95129044:G:GT	donor_gain	0.9000
11:95130335:G:A	acceptor_gain	0.8900
11:95128450:G:GT	donor_gain	0.8700
11:95132357:C:G	acceptor_gain	0.8700
11:95105908:G:GT	donor_gain	0.8600
11:95128372:T:TA	acceptor_gain	0.8600
11:95130334:T:A	acceptor_gain	0.8600
11:95128450:G:T	donor_gain	0.8500

AlphaMissense

3263 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:95128772:G:C	W232C	0.994
11:95128772:G:T	W232C	0.994
11:95090124:C:A	A66D	0.993
11:95128870:T:G	F265C	0.993
11:95128734:T:A	W220R	0.992
11:95128734:T:C	W220R	0.992
11:95090018:T:C	F31L	0.991
11:95090020:T:A	F31L	0.991
11:95090020:T:G	F31L	0.991
11:95090120:T:C	F65L	0.991
11:95090122:C:A	F65L	0.991
11:95090122:C:G	F65L	0.991
11:95128837:T:C	L254P	0.991
11:95128736:G:C	W220C	0.990
11:95128736:G:T	W220C	0.990
11:95128596:T:A	W174R	0.989
11:95128596:T:C	W174R	0.989
11:95128870:T:C	F265S	0.988
11:95128881:T:A	C269S	0.987
11:95128882:G:C	C269S	0.987
11:95090019:T:G	F31C	0.986
11:95128770:T:A	W232R	0.986
11:95128770:T:C	W232R	0.986
11:95128779:G:C	G235R	0.985
11:95090093:T:A	C56S	0.984
11:95090094:G:C	C56S	0.984
11:95128562:T:A	N162K	0.984
11:95128562:T:G	N162K	0.984
11:95090027:T:A	C34S	0.983
11:95090028:G:C	C34S	0.983

dbSNP variants (sampled 300 via entrez): RS1000026675 (11:95096586 T>C), RS1000198742 (11:95102912 A>G), RS1000243705 (11:95109273 G>A), RS1000369317 (11:95090245 C>A,G,T), RS1000540025 (11:95114526 G>C), RS1000593278 (11:95121186 A>C,G), RS1000633008 (11:95103216 C>T), RS1000723481 (11:95122022 A>C), RS1000891581 (11:95114875 C>G,T), RS1000974941 (11:95091552 C>T), RS1001029414 (11:95098293 T>C), RS1001064481 (11:95128031 A>G), RS1001081755 (11:95097907 C>G,T), RS1001235328 (11:95091900 G>A), RS1001386469 (11:95118095 T>G)

Disease associations

OMIM: gene MIM:619568 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004599_25	Mean platelet volume	6.000000e-20
GCST006979_417	Heel bone mineral density	4.000000e-09
GCST009615_13	Triglyceride levels x loop diuretics use interaction	1.000000e-06
GCST90002385_210	High light scatter reticulocyte count	2.000000e-10
GCST90002386_359	High light scatter reticulocyte percentage of red cells	3.000000e-10
GCST90002395_97	Mean platelet volume	6.000000e-45
GCST90002402_384	Platelet count	3.000000e-11
GCST90002405_289	Reticulocyte count	1.000000e-13
GCST90002406_375	Reticulocyte fraction of red cells	3.000000e-14

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004530	triglyceride measurement
EFO:0007986	reticulocyte count
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066995 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.61	Kd	246.2	nM	CHEMBL5653589
6.60	ED50	249	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148320: Binding affinity to human ENDOD1 incubated for 45 mins by Kinobead based pull down assay	kd	0.2462	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases expression	3
Acetaminophen	affects expression, increases expression	3
Benzo(a)pyrene	increases expression, affects methylation	2
Doxorubicin	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Rotenone	increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Aflatoxin B1	increases methylation, increases expression	2
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
pyrvinium	decreases reaction, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
gedatolisib	decreases reaction, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651362	Binding	Binding affinity to human ENDOD1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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