ENDOG

Summary

ENDOG (endonuclease G, HGNC:3346) is a protein-coding gene on chromosome 9q34.11, encoding Endonuclease G, mitochondrial (Q14249). Endonuclease that preferentially catalyzes the cleavage of double-stranded 5-hydroxymethylcytosine (5hmC)-modified DNA.

The protein encoded by this gene is a nuclear encoded endonuclease that is localized in the mitochondrion. The encoded protein is widely distributed among animals and cleaves DNA at GC tracts. This protein is capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA.

Source: NCBI Gene 2021 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 58 total
• Druggable target: yes
• MANE Select transcript: NM_004435

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3346
Approved symbol	ENDOG
Name	endonuclease G
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167136
Ensembl biotype	protein_coding
OMIM	600440
Entrez	2021

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000372642, ENST00000854121

RefSeq mRNA: 1 — MANE Select: NM_004435 NM_004435

CCDS: CCDS6912

Canonical transcript exons

ENST00000372642 — 3 exons

Exon	Start	End
ENSE00001110217	128820739	128820848
ENSE00001458288	128822328	128822676
ENSE00001458291	128818500	128819185

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 96.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.1457 / max 91.3627, expressed in 1743 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98842	6.4816	1647
98841	3.6641	1536

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	96.38	gold quality
apex of heart	UBERON:0002098	96.25	gold quality
gastrocnemius	UBERON:0001388	95.87	gold quality
triceps brachii	UBERON:0001509	95.17	gold quality
body of tongue	UBERON:0011876	94.98	gold quality
muscle of leg	UBERON:0001383	94.90	gold quality
muscle organ	UBERON:0001630	94.54	gold quality
vastus lateralis	UBERON:0001379	94.15	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.85	gold quality
quadriceps femoris	UBERON:0001377	93.82	gold quality
skeletal muscle tissue	UBERON:0001134	93.04	gold quality
diaphragm	UBERON:0001103	93.02	silver quality
biceps brachii	UBERON:0001507	92.86	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.78	gold quality
mucosa of transverse colon	UBERON:0004991	92.23	gold quality
heart left ventricle	UBERON:0002084	92.17	gold quality
cardiac ventricle	UBERON:0002082	92.01	gold quality
gluteal muscle	UBERON:0002000	91.73	gold quality
right lobe of liver	UBERON:0001114	91.36	gold quality
epithelium of bronchus	UBERON:0002031	90.94	gold quality
right atrium auricular region	UBERON:0006631	90.66	gold quality
bronchus	UBERON:0002185	90.49	gold quality
bronchial epithelial cell	CL:0002328	90.47	gold quality
muscle tissue	UBERON:0002385	89.72	gold quality
cardiac atrium	UBERON:0002081	89.42	gold quality
heart	UBERON:0000948	89.05	gold quality
deltoid	UBERON:0001476	89.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.74	gold quality
heart right ventricle	UBERON:0002080	88.29	gold quality
tongue	UBERON:0001723	88.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.69

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 39)

• examination of submitochondrial localization and its ability to cleave R-loops in order to clarify role in mtDNA replication (PMID:12444964)
• endonuclease G and apoptosis-inducing factor are relocated and have roles in calcium induced signaling and oxidative stress-related impairment of mitochondria (PMID:15182854)
• EndoG forms complexes with AIF and FEN-1 but not with PCNA. Heat shock proteins 70 interact with EndoG and are involved in the regulation of its activity. (PMID:16133872)
• Our findings suggest that the presence of EndoG in non-invasive breast cancer cells determines their sensitivity to apoptosis, which may be taken into consideration for developing the chemotherapeutic strategy for cancer treatment. (PMID:17046751)
• Hypochlorous acid induced Bax-dependent mitochondrial permeability which led to cell death without caspase activity by processes involving AIF/EndoG-dependent pathways. (PMID:17107772)
• study of cellular localization of the endonuclease G, AIF & AMID during apoptosis using bioinformatics and image analysis (PMID:17347867)
• EndoG inactivation by loss of expression may not occur in colorectal and gastric cancers. Rather, neo-expression of EndoG may play a role in both colorectal and gastric tumorigenesis. (PMID:18705403)
• data showed that loss of EndoG expression is a feature of hepatocellular carcinomas (PMID:18754329)
• These results suggest that Bim, Bcl-xL, FAK and endonuclease G are involved in safingol-induced apoptosis of detached oral squamous cell carcinoma. (PMID:19199036)
• Results suggest that human Endonuclease G shares a similar catalytic mechanism with nuclease A from Anabaena. (PMID:19272175)
• nuclear translocation of apoptosis-inducing factor and endonuclease G play a crucial role in (-)-Epigallocatechin-3-gallate -induced apoptosis of human laryngeal epidermoid carcinoma Hep2 cells (PMID:19781850)
• When EndoG gene expression was downregulated by lentiviral shRNA vectors, we found a significant reduction in the replicative life span and a corresponding increase in cell death. (PMID:20211237)
• ENDOG might contribute to cancer pathogenesis by expressional alterations, but not by somatic mutations (PMID:21080888)
• Benzyl isothiocyanate induces apoptosis in DU 145 cells through the release of AIF and Endo G from the mitochondria and also promotes caspase-3 activation. (PMID:21206973)
• Data show that among the 13 SNPs in the 3 genes, only 3 were found to be polymorphic: R196K and K277R in the DFFB gene, and S12L in the EndoG gene, and all 6 SNPs in the FEN-1 gene were entirely monoallelic. (PMID:22011247)
• Conclude that EndoG and TOPO2a may actively participate in apoptotic chromatin degradation. (PMID:22160858)
• Ethyl gallate induces apoptosis of HL-60 cells by promoting the expression of caspases-8, -9, -3, apoptosis-inducing factor and endonuclease G. (PMID:23109891)
• CHIP overexpression reduces EndoG levels, and results in reduced or no oxidative stress-induced cell death in cultured cancer cells. (PMID:23764847)
• These data indicate that HSV-1 UL12.5 deploys cellular proteins, including ENDOG and EXOG, to destroy mtDNA and contribute to a growing body of literature highlighting roles for ENDOG and EXOG in mtDNA maintenance. (PMID:23986585)
• Using gene reporter assays, we show that promoter variations in 11 intrinsic apoptosis genes, including ADPRT, APAF1, BCL2, BAD, BID, MCL1, BIRC4, BCL2L1, ENDOG, YWHAB, and YWHAQ, influence promoter activity in an allele-specific manner. (PMID:24038028)
• Endonuclease G mediates alpha-synuclein cytotoxicity during Parkinson’s disease. (PMID:24129513)
• Data indicate that older muscles showed a 3-fold greater fraction of endonuclease G (a mitochondrial proapoptotic factor)-positive myonuclei. (PMID:24371120)
• Endonuclease G (EndoG), an apoptotic nuclease, as an essential factor for MLLbcr-specific DNA recombination after induction of replication stress. (PMID:25132265)
• study demonstrate EndoG interacts with cellular Inhibitor of Apoptosis Protein 1 (cIAP1); results indicate IAPs interact and ubiquitinate EndoG via K63-mediated isopeptide linkages without affecting EndoG levels and EndoG-mediated cell death, suggesting EndoG ubiquitination by IAPs may serve as a regulatory signal independent of proteasomal degradation (PMID:25139236)
• Data suggest that endonuclease G (EndoG) inhibitors have the potential to be utilized for amelioration of cell injuries in which participation of EndoG is essential. (PMID:25401220)
• Results show that BNIP3 interacts with the voltage-dependent anion channel (VDAC) to directly induce mitochondrial release and nuclear translocation of EndoG. (PMID:25436615)
• our study established a link between Endo G and mitochondrial function during cardiac hypertrophy (PMID:26492643)
• These findings suggest that non-viral DNA vectors are also substrates for EndoG in its role in homologous recombination (PMID:27239850)
• EndoG is not a mediator of exogenous DNA clearance, but in non-physiological circumstances, it may nonspecifically cleave intracellular DNA regardless of its origin. (PMID:27260396)
• Overexpression of EndoG in capital ES, Cyrillicsmall a, Cyrilliccapital ES, Cyrillicsmall o, Cyrillic-2 cells downregulated the expression of active full-length hTERT variant and upregulated non-active spliced variant. (PMID:27420614)
• ndoG digests long non-coding RNA and produces 47-mer RNA oligonucleotide complementary to hTERT pre-mRNA exon 8 and intron 8 junction place. Interaction of 47-mer RNA oligonucleotide and hTERT pre-mRNA causes alternative splicing. (PMID:27797329)
• Galectin-3-induced cell death in HIV-1-infected macrophages is most likely related to the translocation of Endo G from the cytoplasm to the nucleus. (PMID:27981746)
• Overexpression of EndoG in CD4+ T cells downregulated the expression of the active full-length hTERT variant and upregulated the inactive alternatively spliced variant. (PMID:28320284)
• EndoG is an endonuclease with the unique ability to inactivate another endonuclease, DNase I, and to modulate the development of apoptosis. (PMID:30521874)
• Autophagy restricts mitochondrial DNA damage-induced release of ENDOG (endonuclease G) to regulate genome stability. (PMID:33465003)
• Assessment of the Role of Nuclear ENDOG Gene and mtDNA Variations on Paternal Mitochondrial Elimination (PME) in Infertile Men: An Experimental Study. (PMID:35477840)
• Unleashing a novel function of Endonuclease G in mitochondrial genome instability. (PMID:36394256)
• Endonuclease G promotes preeclampsia by regulating the Wnt signaling pathway. (PMID:36852641)
• Apoptotic endonuclease EndoG induces alternative splicing of Caspase-2. (PMID:39239896)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	endog	ENSDARG00000058865
mus_musculus	Endog	ENSMUSG00000015337
rattus_norvegicus	Endog	ENSRNOG00000016033
drosophila_melanogaster	EndoG	FBGN0033690
drosophila_melanogaster	Tengl4	FBGN0037857
drosophila_melanogaster	Tengl2	FBGN0052463
caenorhabditis_elegans	cps-6	WBGENE00000787

Paralogs (1): EXOG (ENSG00000157036)

Protein

Protein identifiers

Endonuclease G, mitochondrial — Q14249 (reviewed: Q14249)

All UniProt accessions (2): Q14249, E5KNL5

UniProt curated annotations — full annotation on UniProt →

Function. Endonuclease that preferentially catalyzes the cleavage of double-stranded 5-hydroxymethylcytosine (5hmC)-modified DNA. The 5hmC-modified nucleotide does not increase the binding affinity, but instead increases the efficiency of cutting and specifies the site of cleavage for the modified DNAs. Shows significantly higher affinity for four-stranded Holliday junction over duplex and single-stranded DNAs. Promotes conservative recombination when the DNA is 5hmC-modified. Promotes autophagy through the suppression of mTOR by its phosphorylation-mediated interaction with YWHAG and its endonuclease activity-mediated DNA damage response. GSK3-beta mediated phosphorylation of ENDOG enhances its interaction with YWHAG, leading to the release of TSC2 and PIK3C3 from YWHAG resulting in mTOR pathway suppression and autophagy initiation. Promotes cleavage of mtDNA in response to oxidative and nitrosative stress, in turn inducing compensatory mtDNA replication.

Subunit / interactions. Homodimer; disulfide-linked. Homodimerization is essential for enzyme activity. Interacts with YWHAG.

Subcellular location. Mitochondrion.

Post-translational modifications. GSK3-beta-mediated dual phosphorylations at Thr-128 and Ser-288 is necessary for its interaction with YWHAG and the induction of autophagy.

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

RefSeq proteins (1): NP_004426* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001604	Endo_G_ENPP1-like_dom	Domain
IPR018524	DNA/RNA_endonuclease_AS	Active_site
IPR020821	ENPP1-3/EXOG-like_nuc-like	Domain
IPR040255	Non-specific_endonuclease	Family
IPR044925	His-Me_finger_sf	Homologous_superfamily
IPR044929	DNA/RNA_non-sp_Endonuclease_sf	Homologous_superfamily

Pfam: PF01223

UniProt features (16 total): mutagenesis site 4, sequence conflict 2, modified residue 2, transit peptide 1, chain 1, region of interest 1, active site 1, binding site 1, site 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14249-F1	85.67	0.74

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 (2): 141 (proton acceptor); 110 (essential for catalytic activity)

Ligand- & substrate-binding residues (1): 172

Post-translational modifications (2): 128, 288

Disulfide bonds (1): 113

Mutagenesis-validated functional residues (4):

Position	Phenotype
128	loss of phosphorylation. suppresses interaction with ywhag and induction of autophagy; when associated with a-288.
128	phosphomimetic mutant. no effect on its interaction with ywhag. enhances interaction with ywhag; when associated with t-
288	loss of phosphorylation. suppresses interaction with ywhag and induction of autophagy; when associated with a-128.
288	phosphomimetic mutant. no effect on its interaction with ywhag. enhances interaction with ywhag; when associated with t-

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 201 (showing top): GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_AUTOPHAGY, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_RESPONSE_TO_PEPTIDE, GOMF_NUCLEASE_ACTIVITY, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_MITOCHONDRIAL_DNA_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP

GO Biological Process (20): in utero embryonic development (GO:0001701), apoptotic DNA fragmentation (GO:0006309), DNA recombination (GO:0006310), DNA damage response (GO:0006974), response to mechanical stimulus (GO:0009612), positive regulation of autophagy (GO:0010508), negative regulation of TOR signaling (GO:0032007), mitochondrial DNA catabolic process (GO:0032043), response to estradiol (GO:0032355), cellular response to oxidative stress (GO:0034599), response to tumor necrosis factor (GO:0034612), positive regulation of apoptotic process (GO:0043065), response to antibiotic (GO:0046677), cellular response to calcium ion (GO:0071277), cellular response to glucose stimulus (GO:0071333), cellular response to hypoxia (GO:0071456), positive regulation of mitochondrial DNA replication (GO:0090297), positive regulation of hydrogen peroxide-mediated programmed cell death (GO:1901300), positive regulation of apoptotic DNA fragmentation (GO:1902512), DNA catabolic process (GO:0006308)

GO Molecular Function (12): single-stranded DNA endonuclease activity (GO:0000014), magnesium ion binding (GO:0000287), nucleic acid binding (GO:0003676), DNA endonuclease activity (GO:0004520), RNA endonuclease activity (GO:0004521), protein homodimerization activity (GO:0042803), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), DNA nuclease activity (GO:0004536), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), perikaryon (GO:0043204), perinuclear region of cytoplasm (GO:0048471)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA catabolic process	2
DNA metabolic process	2
cellular response to stress	2
positive regulation of programmed cell death	2
DNA nuclease activity	2
binding	2
endonuclease activity	2
nuclease activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
cellular anatomical structure	2
chordate embryonic development	1
apoptotic nuclear changes	1
response to external stimulus	1
response to abiotic stimulus	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
TOR signaling	1
regulation of TOR signaling	1
negative regulation of intracellular signal transduction	1
mitochondrion	1
mitochondrial DNA metabolic process	1
response to lipid	1
response to oxygen-containing compound	1
response to oxidative stress	1
cellular response to chemical stress	1
response to cytokine	1
apoptotic process	1
regulation of apoptotic process	1
response to chemical	1
response to calcium ion	1
cellular response to metal ion	1
intracellular glucose homeostasis	1
response to glucose	1
cellular response to hexose stimulus	1
response to hypoxia	1
cellular response to decreased oxygen levels	1
mitochondrial DNA replication	1
regulation of mitochondrial DNA replication	1

Protein interactions and networks

STRING

1564 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENDOG	CYCS	P00001	938
ENDOG	DIABLO	Q9NR28	908
ENDOG	SPOUT1	Q5T280	855
ENDOG	AIFM1	O95831	854
ENDOG	TBC1D13	Q9NVG8	838
ENDOG	HTRA2	O43464	807
ENDOG	KYAT1	Q16773	783
ENDOG	DFFA	O00273	768
ENDOG	CASP9	P55211	746
ENDOG	APAF1	O14727	744
ENDOG	BCL2	P10415	708
ENDOG	DFFB	O76075	706
ENDOG	RASSF6	Q6ZTQ3	698
ENDOG	CASP3	P42574	690
ENDOG	FEN1	P39748	673

IntAct

78 interactions, top by confidence:

A	B	Type	Score
NFYC	NFYA	psi-mi:“MI:0914”(association)	0.850
PCGF2	CBX4	psi-mi:“MI:0914”(association)	0.840
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
DNAJB4	DNAJB5	psi-mi:“MI:0914”(association)	0.730
DNAJA4	DNAJA2	psi-mi:“MI:0914”(association)	0.710
ITLN2	ENDOG	psi-mi:“MI:0915”(physical association)	0.640
EPHA8	EFNA5	psi-mi:“MI:0914”(association)	0.610
PRKACG	UBB	psi-mi:“MI:0914”(association)	0.530
BAG4	DNAJC13	psi-mi:“MI:0914”(association)	0.530
DNAJA1	HERC2	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
PSME1	POLR3A	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
DNAJA1	DNAJA2	psi-mi:“MI:0914”(association)	0.530
ITLN1	HSPA5	psi-mi:“MI:0914”(association)	0.530
HSPA2	DNAJC13	psi-mi:“MI:0914”(association)	0.530
DNAJA4	ENDOG	psi-mi:“MI:0915”(physical association)	0.500
TNKS	ENDOG	psi-mi:“MI:0407”(direct interaction)	0.440
AIFM1	HAX1	psi-mi:“MI:2364”(proximity)	0.420
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420

BioGRID (104): BIRC2 (Affinity Capture-Western), ENDOG (Affinity Capture-MS), ENDOG (Affinity Capture-MS), ENDOG (Affinity Capture-MS), ENDOG (Affinity Capture-MS), ENDOG (Affinity Capture-MS), ENDOG (Affinity Capture-MS), ENDOG (Affinity Capture-MS), DKC1 (Co-fractionation), ENDOG (Affinity Capture-MS), ENDOG (Affinity Capture-MS), ENDOG (Affinity Capture-MS), ENDOG (Affinity Capture-MS), ENDOG (Affinity Capture-MS), ENDOG (Affinity Capture-MS)

ESM2 similar proteins: A1A4L8, A2BDX3, A4RPM5, A5GFZ6, A6NK58, B0W377, B3MLX7, B4FAT0, B4LRB9, B4N7R4, B4NXF7, B6TNK6, D3KU66, D3KU67, O08600, O19179, O43323, O95396, P22989, P29038, P52785, P55203, P85971, Q02846, Q08DH8, Q0VFH3, Q14249, Q14BV6, Q17CA7, Q3KQV9, Q3TW96, Q561R2, Q58E95, Q5K4L6, Q5PQQ1, Q5ZKI2, Q61488, Q6PAT0, Q7PY41, Q7QFL7

Diamond homologs: O08600, P08466, P38446, P38447, P81203, P81204, Q0IH72, Q10480, Q14249, Q502K1, Q8C163, Q95NM6, Q9Y2C4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ENDOG	up-regulates	BAX
BIRC2	“up-regulates activity”	ENDOG	ubiquitination
BAK1	up-regulates	ENDOG

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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
Regulation of HSF1-mediated heat shock response	7	17.4×	6e-05
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	5	17.3×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein refolding	6	49.3×	9e-07
response to heat	5	27.7×	2e-04
response to unfolded protein	5	19.8×	8e-04
protein folding	10	13.6×	9e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1013 predictions. Top by Δscore:

Variant	Effect	Δscore
9:128820737:A:AC	acceptor_loss	1.0000
9:128820737:A:AG	acceptor_gain	1.0000
9:128820738:G:GG	acceptor_gain	1.0000
9:128819181:CCCAG:C	donor_loss	0.9900
9:128819182:CCAG:C	donor_loss	0.9900
9:128819183:CAGG:C	donor_loss	0.9900
9:128819184:AGGT:A	donor_loss	0.9900
9:128819185:GG:G	donor_loss	0.9900
9:128819186:G:GA	donor_loss	0.9900
9:128819187:T:A	donor_loss	0.9900
9:128820737:AG:A	acceptor_gain	0.9900
9:128820737:AGGT:A	acceptor_gain	0.9900
9:128820738:GG:G	acceptor_gain	0.9900
9:128820738:GGT:G	acceptor_gain	0.9900
9:128820738:GGTG:G	acceptor_gain	0.9900
9:128820738:GGTGC:G	acceptor_gain	0.9900
9:128822109:CCAG:C	acceptor_gain	0.9900
9:128820734:A:AG	acceptor_gain	0.9800
9:128822326:A:AG	acceptor_gain	0.9800
9:128822327:G:GG	acceptor_gain	0.9800
9:128820735:C:G	acceptor_gain	0.9700
9:128822327:GGACA:G	acceptor_gain	0.9700
9:128820734:ACCAG:A	acceptor_gain	0.9600
9:128820849:G:GG	donor_gain	0.9600
9:128821509:G:GT	donor_gain	0.9600
9:128821999:CACCT:C	acceptor_gain	0.9500
9:128822121:A:C	acceptor_gain	0.9500
9:128822354:TAAAG:T	acceptor_gain	0.9500
9:128822357:AGTAC:A	acceptor_gain	0.9500
9:128822322:CCACA:C	acceptor_loss	0.9400

AlphaMissense

1889 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:128819159:T:C	F159L	0.999
9:128819161:C:A	F159L	0.999
9:128819161:C:G	F159L	0.999
9:128819173:C:A	N163K	0.999
9:128819173:C:G	N163K	0.999
9:128820763:T:A	W176R	0.999
9:128820763:T:C	W176R	0.999
9:128819027:T:C	F115L	0.998
9:128819029:C:A	F115L	0.998
9:128819029:C:G	F115L	0.998
9:128819168:A:C	S162R	0.998
9:128819170:C:A	S162R	0.998
9:128819170:C:G	S162R	0.998
9:128820765:G:C	W176C	0.998
9:128820765:G:T	W176C	0.998
9:128820776:A:T	E180V	0.998
9:128820830:G:A	G198E	0.998
9:128822409:G:C	K231N	0.998
9:128822409:G:T	K231N	0.998
9:128822469:C:A	N251K	0.998
9:128822469:C:G	N251K	0.998
9:128818964:T:A	W94R	0.997
9:128818964:T:C	W94R	0.997
9:128819028:T:G	F115C	0.997
9:128819105:C:G	H141D	0.997
9:128819107:C:A	H141Q	0.997
9:128819107:C:G	H141Q	0.997
9:128819112:C:A	A143D	0.997
9:128820777:G:C	E180D	0.997
9:128820777:G:T	E180D	0.997

dbSNP variants (sampled 300 via entrez): RS1000377291 (9:128819721 A>C), RS1000742076 (9:128819925 C>T), RS1002121987 (9:128817105 A>C,G), RS1002880121 (9:128819336 C>G,T), RS1003795098 (9:128823165 G>A,C), RS1004126732 (9:128822998 C>T), RS1004175835 (9:128819418 T>A), RS1006146926 (9:128822035 C>G), RS1006178260 (9:128821817 A>G), RS1006223644 (9:128821947 C>T), RS1006508111 (9:128816526 TCACTTG>T), RS1006761992 (9:128821875 C>T), RS1007157532 (9:128823057 C>T), RS1007318197 (9:128820460 C>T), RS1008099180 (9:128818973 G>A)

Disease associations

OMIM: gene MIM:600440 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST006879_1	Blood metabolite levels	1.000000e-09
GCST006879_18	Blood metabolite levels	3.000000e-43
GCST006879_19	Blood metabolite levels	4.000000e-83
GCST006879_2	Blood metabolite levels	2.000000e-12
GCST006879_20	Blood metabolite levels	5.000000e-12
GCST006879_21	Blood metabolite levels	2.000000e-22
GCST006879_22	Blood metabolite levels	2.000000e-20

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3804749 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
Quercetin	affects cotreatment, increases expression	3
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	3
Resveratrol	affects localization, decreases reaction	2
Acetylcysteine	decreases reaction, increases localization, affects cotreatment, affects localization	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Cyclosporine	decreases expression	2
cationic amphipathic peptide RT2	increases expression	1
lupiwighteone	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
danthron	affects localization, increases expression	1
naringin	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	increases expression	1
lead acetate	decreases expression	1
tetrandrine	decreases expression	1
perfosfamide	decreases reaction, increases localization, increases response to substance, increases expression	1
trichostatin A	increases expression	1
sulforaphane	increases expression	1
fisetin	increases localization	1
cobaltous chloride	decreases expression	1
bufalin	increases expression	1
3,3’,4,5’-tetrahydroxystilbene	affects localization, decreases reaction	1
beta-methylcholine	affects expression	1
celastrol	increases expression	1
casticin	decreases expression	1
di-n-butylphosphoric acid	affects 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
CHEMBL3807465	Binding	Activation of endonuclease G in human HL60 cells at 0.1 to 1 uM after 48 hrs by Western blot analysis	5-Ene-4-thiazolidinones induce apoptosis in mammalian leukemia cells. — Eur J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SM01	HAP1 ENDOG (-) 1	Cancer cell line	Male
CVCL_SM02	HAP1 ENDOG (-) 2	Cancer cell line	Male
CVCL_SM03	HAP1 ENDOG (-) 3	Cancer cell line	Male
CVCL_SM04	HAP1 ENDOG (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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