ENTPD5

Summary

ENTPD5 (ectonucleoside triphosphate diphosphohydrolase 5 (inactive), HGNC:3367) is a protein-coding gene on chromosome 14q24.3, encoding Nucleoside diphosphate phosphatase ENTPD5 (O75356). Hydrolyzes nucleoside diphosphates with a preference for GDP, IDP and UDP compared to ADP and CDP.

The protein encoded by this gene is similar to E-type nucleotidases (NTPases)/ecto-ATPase/apyrases. NTPases, such as CD39, mediate catabolism of extracellular nucleotides. ENTPD5 contains 4 apyrase-conserved regions which is characteristic of NTPases.

Source: NCBI Gene 957 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 111 total — 2 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001249

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3367
Approved symbol	ENTPD5
Name	ectonucleoside triphosphate diphosphohydrolase 5 (inactive)
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	NTPDase-5
Ensembl gene	ENSG00000187097
Ensembl biotype	protein_coding
OMIM	603162
Entrez	957

Gene structure

Transcript identifiers

Ensembl transcripts: 59 — 56 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000334696, ENST00000553284, ENST00000554664, ENST00000555829, ENST00000556108, ENST00000556242, ENST00000557325, ENST00000557681, ENST00000900873, ENST00000900874, ENST00000900875, ENST00000900876, ENST00000900877, ENST00000900878, ENST00000900879, ENST00000900880, ENST00000900881, ENST00000900882, ENST00000900883, ENST00000900884, ENST00000900885, ENST00000900886, ENST00000900887, ENST00000900888, ENST00000900889, ENST00000900890, ENST00000900891, ENST00000900892, ENST00000900893, ENST00000900894, ENST00000900895, ENST00000900896, ENST00000900897, ENST00000900898, ENST00000900899, ENST00000900900, ENST00000900901, ENST00000900902, ENST00000900903, ENST00000900904, ENST00000900905, ENST00000900906, ENST00000900907, ENST00000900908, ENST00000900909, ENST00000900910, ENST00000900911, ENST00000900912, ENST00000900913, ENST00000900914, ENST00000900915, ENST00000900916, ENST00000900917, ENST00000900918, ENST00000900919, ENST00000928046, ENST00000971785, ENST00000971786, ENST00000971787

RefSeq mRNA: 14 — MANE Select: NM_001249 NM_001249, NM_001321984, NM_001321985, NM_001321986, NM_001321987, NM_001321988, NM_001330189, NM_001382256, NM_001382257, NM_001382258, NM_001382259, NM_001382260, NM_001382262, NM_001382263

CCDS: CCDS81825, CCDS9825

Canonical transcript exons

ENST00000334696 — 16 exons

Exon	Start	End
ENSE00001331467	73970010	73970125
ENSE00001331468	73971852	73971908
ENSE00001331470	73972884	73973024
ENSE00001331473	73974924	73974985
ENSE00001331480	73975936	73976015
ENSE00001331482	73976324	73976412
ENSE00001331484	73977024	73977059
ENSE00001331488	73977299	73977374
ENSE00001331490	73983018	73983161
ENSE00001331493	73986814	73986893
ENSE00001331499	73963230	73967014
ENSE00001331508	73987886	73988172
ENSE00001367344	73973877	73973978
ENSE00001413071	74011091	74011150
ENSE00001413534	74015824	74015930
ENSE00002222689	74019250	74019288

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 97.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.8509 / max 108.4542, expressed in 1560 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144010	3.2551	1558
144008	0.4021	37
144009	0.1937	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	97.92	gold quality
colonic mucosa	UBERON:0000317	97.90	gold quality
rectum	UBERON:0001052	97.82	gold quality
jejunal mucosa	UBERON:0000399	97.30	gold quality
duodenum	UBERON:0002114	94.96	gold quality
liver	UBERON:0002107	94.64	gold quality
mucosa of transverse colon	UBERON:0004991	94.44	gold quality
right lobe of liver	UBERON:0001114	93.85	gold quality
transverse colon	UBERON:0001157	90.28	gold quality
adult mammalian kidney	UBERON:0000082	90.09	gold quality
colonic epithelium	UBERON:0000397	90.04	gold quality
esophagus squamous epithelium	UBERON:0006920	89.86	gold quality
jejunum	UBERON:0002115	88.38	gold quality
kidney	UBERON:0002113	87.96	gold quality
ileal mucosa	UBERON:0000331	87.95	gold quality
renal medulla	UBERON:0000362	87.70	gold quality
large intestine	UBERON:0000059	87.27	gold quality
intestine	UBERON:0000160	87.25	gold quality
small intestine	UBERON:0002108	86.95	gold quality
colon	UBERON:0001155	86.93	gold quality
epithelium of esophagus	UBERON:0001976	86.45	gold quality
prostate gland	UBERON:0002367	86.36	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.28	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.14	gold quality
urethra	UBERON:0000057	85.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.31	gold quality
oral cavity	UBERON:0000167	84.17	gold quality
adult organism	UBERON:0007023	84.06	gold quality
gall bladder	UBERON:0002110	83.70	gold quality
metanephros cortex	UBERON:0010533	83.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	254.42
E-ANND-3	yes	6.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

140 targeting ENTPD5, 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-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-539-5P	99.93	70.30	2855

Literature-anchored findings (GeneRIF, showing 15)

• deregulation and loss of expression in the progression of laryngeal neoplasia [PCPH] (PMID:12489110)
• Results positively identify PCPH as a good early molecular marker for testicular neoplasms, and strongly indicate that immunodetection of truncated PCPH polypeptides may be a useful diagnostic tool for testicular germ cell tumors. (PMID:16465363)
• PCPH/ENTPD5 expression enhances the invasiveness of human prostate cancer cells by a protein kinase C delta-dependent mechanism (PMID:18006831)
• Findings identify PCPH as an important participant in the chemotherapy response of prostate cancer cells and establish a role for PCPH-PKCalpha-Bcl-2 functional interactions in the drug response process. (PMID:19117992)
• Study reports that ENTPD5, an endoplasmic reticulum (ER) enzyme, is upregulated in cell lines and primary human tumor samples with active AKT. (PMID:21074248)
• The elevation of ENTPD5 activity therefore protects AKT-active cancer cells from protein-overloading-induced endoplasmic reticulum stress and the resulting growth arrest and apoptosis. (PMID:22169232)
• Upregulation of ENTPD5 is associated with altered metabolism in gliomablastoma multiforme. (PMID:22992974)
• These results strongly suggest that the mt-PCPH ( ENTPD5)oncoprotein may regulate the cellular energy levels and subsequent chemoresistance by an NTPDase-independent mechanism (PMID:23921441)
• The main point of this review is to integrate the findings and proposed theories about the role played by NTPDase5/mt-PCPH in cancer progression, considering that these proteins have been suggested as potential early diagnostic tools and therapy targets. (PMID:25045656)
• Results suggest that ENTPD5 affects lung cancer apoptosis via Caspase 3 pathway, and can be potentially used to monitor prognosis or to guide appropriate therapeutic regimens. (PMID:25794010)
• ENTPD5 is a mediator of mutant p53 gain of function activity in clonogenic growth, architectural tissue remodeling, migration, invasion, and lung colonization in lung cancer and its mouse models (PMID:27956623)
• [ENTPD5 gene is highly expressed in epithelial ovarian cancer: analysis based on Oncomine database and bioinformatics]. (PMID:33963715)
• ENTPD5: identification of splicing variants and their impact on cancer survival. (PMID:34075526)
• ENTPD5 splice variants: novel players in cancer? (PMID:34272651)
• The UDPase ENTPD5 regulates ER stress-associated renal injury by mediating protein N-glycosylation. (PMID:36849424)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	entpd5a	ENSDARG00000053481
danio_rerio	entpd5b	ENSDARG00000093659
mus_musculus	Entpd5	ENSMUSG00000021236
rattus_norvegicus	Entpd5	ENSRNOG00000033206
drosophila_melanogaster	NTPase	FBGN0024947
caenorhabditis_elegans		WBGENE00010697

Paralogs (7): ENTPD2 (ENSG00000054179), ENTPD1 (ENSG00000138185), ENTPD3 (ENSG00000168032), ENTPD8 (ENSG00000188833), ENTPD4 (ENSG00000197217), ENTPD6 (ENSG00000197586), ENTPD7 (ENSG00000198018)

Protein

Protein identifiers

Nucleoside diphosphate phosphatase ENTPD5 — O75356 (reviewed: O75356)

Alternative names: CD39 antigen-like 4, ER-UDPase, Ectonucleoside triphosphate diphosphohydrolase 5, Guanosine-diphosphatase ENTPD5, Inosine diphosphate phosphatase ENTPD5, Nucleoside diphosphatase, Uridine-diphosphatase ENTPD5

All UniProt accessions (5): O75356, G3V3Y0, G3V450, G3V4I0, H0YJH1

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes nucleoside diphosphates with a preference for GDP, IDP and UDP compared to ADP and CDP. In the lumen of the endoplasmic reticulum, hydrolyzes UDP that acts as an end-product feedback inhibitor of the UDP-Glc:glycoprotein glucosyltransferases. UMP can be transported back by an UDP-sugar antiporter to the cytosol where it is consumed to regenerate UDP-glucose. Therefore, it positively regulates protein reglucosylation by clearing UDP from the ER lumen and by promoting the regeneration of UDP-glucose. Protein reglucosylation is essential to proper glycoprotein folding and quality control in the ER.

Subunit / interactions. Monomer; active form. Homodimer; disulfide-linked. Homodimers are enzymatically inactive.

Subcellular location. Endoplasmic reticulum. Secreted.

Tissue specificity. Expressed in adult liver, kidney, prostate, testis and colon. Much weaker expression in other tissues.

Post-translational modifications. N-glycosylated; high-mannose type. Glycosylation is not essential for enzymatic activity.

Induction. Up-regulated in cell lines and primary tumor samples with active AKT1.

Pathway. Protein modification; protein glycosylation.

Miscellaneous. May mediate some of the cancer-related phenotypes associated with AKT1 activation: its up-regulation by AKT1 leads to the elevation of aerobic glycolysis seen in tumor cells, a phenomenon known as the Warburg effect.

Similarity. Belongs to the GDA1/CD39 NTPase family.

RefSeq proteins (14): NP_001240, NP_001308913, NP_001308914, NP_001308915, NP_001308916, NP_001308917, NP_001317118, NP_001369185, NP_001369186, NP_001369187, NP_001369188, NP_001369189, NP_001369191, NP_001369192 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000407	GDA1_CD39_NTPase	Family

Pfam: PF01150

Catalyzed reactions (Rhea), 6 shown:

• GDP + H2O = GMP + phosphate + H(+) (RHEA:22156)
• IDP + H2O = IMP + phosphate + H(+) (RHEA:35207)
• a ribonucleoside 5’-diphosphate + H2O = a ribonucleoside 5’-phosphate + phosphate + H(+) (RHEA:36799)
• ADP + H2O = AMP + phosphate + H(+) (RHEA:61436)
• UDP + H2O = UMP + phosphate + H(+) (RHEA:64876)
• CDP + H2O = CMP + phosphate + H(+) (RHEA:64880)

UniProt features (24 total): binding site 15, glycosylation site 2, disulfide bond 2, signal peptide 1, chain 1, active site 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75356-F1	87.55	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 (1): 172 (proton acceptor)

Ligand- & substrate-binding residues (15): 202; 202; 202; 203; 203; 204; 204; 331; 57; 57; 57; 58 …

Disulfide bonds (2): 272–303, 363–377

Glycosylation sites (2): 232, 368

Mutagenesis-validated functional residues (1):

Position	Phenotype
39	no effect on protein stability. no effect on nucleoside-diphosphatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8850843	Phosphate bond hydrolysis by NTPDase proteins
R-HSA-9660826	Purinergic signaling in leishmaniasis infection

MSigDB gene sets: 190 (showing top): GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_1, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_PROTEIN_MATURATION, chr14q24, GOBP_PYRIMIDINE_NUCLEOTIDE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS

GO Biological Process (5): UDP-alpha-D-glucose metabolic process (GO:0006011), UDP catabolic process (GO:0006256), protein N-linked glycosylation (GO:0006487), ‘de novo’ post-translational protein folding (GO:0051084), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (10): GDP phosphatase activity (GO:0004382), CDP phosphatase activity (GO:0036384), ADP phosphatase activity (GO:0043262), UDP phosphatase activity (GO:0045134), IDP phosphatase activity (GO:1990003), nucleotide binding (GO:0000166), protein binding (GO:0005515), ATP binding (GO:0005524), hydrolase activity (GO:0016787), nucleoside diphosphate phosphatase activity (GO:0017110)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Nucleotide catabolism	1
Cell recruitment (pro-inflammatory response)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleoside diphosphate phosphatase activity	5
nucleotide-sugar metabolic process	1
pyrimidine ribonucleoside diphosphate catabolic process	1
pyrimidine ribonucleotide catabolic process	1
UDP metabolic process	1
glycoprotein biosynthetic process	1
‘de novo’ protein folding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
catalytic activity	1
pyrophosphatase activity	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENTPD5	CMPK1	P30085	832
ENTPD5	AK1	P00568	746
ENTPD5	FAM161B	Q96MY7	617
ENTPD5	C2orf72	A6NCS6	479
ENTPD5	PTEN	P60484	465
ENTPD5	ENPP3	O14638	440
ENTPD5	COQ6	Q9Y2Z9	435
ENTPD5	NTPCR	Q9BSD7	434
ENTPD5	MYOZ3	Q8TDC0	418
ENTPD5	ENTPD3	O75355	418
ENTPD5	ENPP1	P22413	404
ENTPD5	ENTPD4	Q9Y227	396
ENTPD5	TPK1	Q9H3S4	395
ENTPD5	THTPA	Q9BU02	394
ENTPD5	ENTPD1	P49961	386

IntAct

24 interactions, top by confidence:

A	B	Type	Score
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
BCHE	ENTPD5	psi-mi:“MI:0914”(association)	0.640
MXI1	ENTPD5	psi-mi:“MI:0915”(physical association)	0.560
ENTPD5	MXI1	psi-mi:“MI:0915”(physical association)	0.560
ENTPD5	HTT	psi-mi:“MI:0915”(physical association)	0.560
ENTPD5	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
ENTPD5	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
BCHE		psi-mi:“MI:0914”(association)	0.350
LYZL2	MANBA	psi-mi:“MI:0914”(association)	0.350
BCHE	SHTN1	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350
LYZL2	ZZEF1	psi-mi:“MI:0914”(association)	0.350
IDS	COCH	psi-mi:“MI:0914”(association)	0.350
CA10	ENTPD5	psi-mi:“MI:0914”(association)	0.350
ENTPD5	ENTPD5	psi-mi:“MI:0914”(association)	0.350

BioGRID (19): MXI1 (Two-hybrid), ENTPD5 (Affinity Capture-MS), ENTPD5 (Affinity Capture-MS), ENTPD5 (Affinity Capture-MS), ENTPD5 (Affinity Capture-MS), ENTPD5 (Affinity Capture-MS), HSPD1 (Proximity Label-MS), HIST2H2BE (Proximity Label-MS), ENTPD5 (Affinity Capture-MS), ENTPD5 (Affinity Capture-MS), ENTPD5 (Affinity Capture-MS), ENTPD5 (Affinity Capture-MS), ENTPD5 (Affinity Capture-MS), ENTPD5 (Affinity Capture-MS), ENTPD5 (Affinity Capture-MS)

ESM2 similar proteins: A0JND9, E1BPW0, O14773, O18956, O35795, O55026, O75173, O75355, O75356, O75578, O89023, O93295, P08514, P08648, P11688, P17405, P49961, P55772, P56201, P79784, P97687, Q04519, Q0VD19, Q12794, Q32M88, Q49HH9, Q49KI5, Q5DRK1, Q5IS74, Q5MY95, Q5RFL1, Q5RFQ8, Q60HH1, Q6P3E7, Q6P6S9, Q717C1, Q717C2, Q7RTX0, Q8BFW6, Q8BNJ2

Diamond homologs: A0JND9, D2GZV9, O18956, O35795, O55026, O75354, O75355, O75356, O93295, P49961, P55772, P79784, P97687, Q3U0P5, Q5DRK1, Q5MY95, Q6NQA8, Q6P6S9, Q8BFW6, Q8H1D8, Q8H7L6, Q8K0L2, Q9ER31, Q9MYU4, Q9QYC8, Q9SQG2, Q9WUZ9, Q9XU84, Q9Y5L3, E1BPW0, E1C1L6, O80612, P32621, P52914, P80595, Q2QYE1, Q6Z4P2, Q8TGG8, Q8TGH6, Q9HEM6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	65
Likely benign	17
Benign	6

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1322156	NM_182476.3(COQ6):c.788_789del (p.Leu262_Ser263insTer)	Pathogenic
375342	NM_182476.3(COQ6):c.763G>A (p.Gly255Arg)	Pathogenic

SpliceAI

4225 predictions. Top by Δscore:

Variant	Effect	Δscore
14:73961154:T:A	acceptor_gain	1.0000
14:73961156:T:TA	acceptor_gain	1.0000
14:73961157:G:A	acceptor_gain	1.0000
14:73961160:T:TA	acceptor_gain	1.0000
14:73961171:AGT:A	acceptor_gain	1.0000
14:73961172:G:GA	acceptor_gain	1.0000
14:73961172:GTG:G	acceptor_gain	1.0000
14:73961453:A:AG	acceptor_gain	1.0000
14:73961454:G:GG	acceptor_gain	1.0000
14:73961564:GACT:G	donor_gain	1.0000
14:73961568:TAGGT:T	donor_loss	1.0000
14:73961569:AGGTA:A	donor_loss	1.0000
14:73961572:T:G	donor_loss	1.0000
14:73961822:GCTC:G	donor_gain	1.0000
14:73961861:G:GT	donor_gain	1.0000
14:73970004:TCTTA:T	donor_loss	1.0000
14:73970005:CTTA:C	donor_loss	1.0000
14:73970006:TTA:T	donor_loss	1.0000
14:73970007:TAC:T	donor_loss	1.0000
14:73970008:A:AT	donor_loss	1.0000
14:73970009:CCTG:C	donor_loss	1.0000
14:73970121:ACACA:A	acceptor_gain	1.0000
14:73970122:CACA:C	acceptor_gain	1.0000
14:73970122:CACAC:C	acceptor_gain	1.0000
14:73970123:ACA:A	acceptor_gain	1.0000
14:73970124:CA:C	acceptor_gain	1.0000
14:73970124:CAC:C	acceptor_gain	1.0000
14:73970125:AC:A	acceptor_loss	1.0000
14:73970126:C:CC	acceptor_gain	1.0000
14:73970126:C:CG	acceptor_loss	1.0000

AlphaMissense

2792 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:73966981:A:G	W412R	0.999
14:73966981:A:T	W412R	0.999
14:73970071:A:G	L380P	0.999
14:73976367:A:G	L200P	0.999
14:73966979:C:A	W412C	0.998
14:73966979:C:G	W412C	0.998
14:73970053:A:G	L386P	0.998
14:73970075:C:G	D379H	0.998
14:73970079:G:C	C377W	0.998
14:73970080:C:T	C377Y	0.998
14:73970081:A:G	C377R	0.998
14:73972904:G:T	A336D	0.998
14:73973949:A:G	C272R	0.998
14:73974971:C:T	G246E	0.998
14:73977048:A:G	W177R	0.998
14:73977048:A:T	W177R	0.998
14:73987921:C:G	R61P	0.998
14:73970074:T:A	D379V	0.997
14:73970074:T:G	D379A	0.997
14:73970080:C:G	C377S	0.997
14:73970081:A:T	C377S	0.997
14:73970122:C:T	C363Y	0.997
14:73971861:C:G	A359P	0.997
14:73972928:G:T	A328D	0.997
14:73973002:G:C	C303W	0.997
14:73973003:C:T	C303Y	0.997
14:73970050:A:G	L387S	0.996
14:73970122:C:G	C363S	0.996
14:73970123:A:G	C363R	0.996
14:73970123:A:T	C363S	0.996

dbSNP variants (sampled 300 via entrez): RS1000030840 (14:74000451 C>A,G,T), RS1000099821 (14:73995814 A>C), RS1000115857 (14:73995043 G>A), RS1000203664 (14:73989936 A>G), RS1000258130 (14:74001228 C>T), RS1000261727 (14:73983443 T>A), RS1000275809 (14:73985403 GTTGT>G), RS1000284355 (14:73970280 T>G), RS1000323734 (14:73973557 T>C), RS1000376729 (14:73983793 C>T), RS1000388352 (14:73955489 A>G), RS1000402525 (14:74017868 G>A), RS1000536980 (14:73991285 T>C), RS1000539803 (14:74019373 C>A,G,T), RS1000629878 (14:73984055 T>TA)

Disease associations

OMIM: gene MIM:603162 | disease phenotypes: MIM:614650

GenCC curated gene-disease

Mondo (1): familial steroid-resistant nephrotic syndrome with sensorineural deafness (MONDO:0013836)

Orphanet (1): Familial steroid-resistant nephrotic syndrome with sensorineural deafness (Orphanet:280406)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005557_1	Serum uric acid levels	3.000000e-06
GCST006585_1896	Blood protein levels	9.000000e-94
GCST010002_156	Refractive error	7.000000e-25

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523151 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 4 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	CHEMBL1736978

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	2
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	decreases expression	1
pentanal	decreases expression	1
octa-2,4,6-trienoic acid	decreases expression	1
abrine	decreases expression	1
LG 100815	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Diclofenac	affects expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Theophylline	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4418828	Binding	Inhibition of human recombinant ENTPD5 expressed in insect cells assessed as reduction in UDP hydrolysis incubated for 1 hr in presence of UMP, GTP and ATP by Escherichia coli UMP kinase pyrH catalyzed UMP phosphorylation coupled luciferase	Entpd5 inhibitors

Clinical trials (associated diseases)

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