P2RX5

Summary

P2RX5 (purinergic receptor P2X 5, HGNC:8536) is a protein-coding gene on chromosome 17p13.2, encoding P2X purinoceptor 5 (Q93086). ATP-gated nonselective transmembrane cation channel permeable to potassium, sodium and calcium.

The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream gene, TAX1BP3 (Tax1 binding protein 3).

Source: NCBI Gene 5026 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 88 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002561

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8536
Approved symbol	P2RX5
Name	purinergic receptor P2X 5
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	P2X5, LRH-1
Ensembl gene	ENSG00000083454
Ensembl biotype	protein_coding
OMIM	602836
Entrez	5026

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000225328, ENST00000345901, ENST00000547178, ENST00000547933, ENST00000549063, ENST00000550772, ENST00000551178, ENST00000552050, ENST00000552276, ENST00000552456, ENST00000552723, ENST00000697413, ENST00000853234, ENST00000971449, ENST00000971450, ENST00000971451

RefSeq mRNA: 8 — MANE Select: NM_002561 NM_001204519, NM_001204520, NM_001425082, NM_001425083, NM_001425084, NM_001425085, NM_002561, NM_175080

CCDS: CCDS11034, CCDS11035, CCDS56014, CCDS56015

Canonical transcript exons

ENST00000225328 — 12 exons

Exon	Start	End
ENSE00001882206	3695869	3696155
ENSE00001929963	3673227	3673877
ENSE00003487474	3690605	3690680
ENSE00003524419	3688012	3688105
ENSE00003525685	3688626	3688759
ENSE00003545900	3690427	3690523
ENSE00003546396	3679590	3679784
ENSE00003551530	3691644	3691794
ENSE00003554991	3690956	3691027
ENSE00003569979	3689492	3689630
ENSE00003578208	3690070	3690150
ENSE00003642841	3681896	3681978

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 98.02.

FANTOM5 (CAGE): breadth broad, TPM avg 3.5317 / max 218.6255, expressed in 721 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163869	1.4166	417
163867	1.0779	331
163868	1.0202	270
163870	0.4028	229
163865	0.0056	1
163866	0.0055	1
163864	0.0033	1
163863	0.0026	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	98.02	gold quality
lymph node	UBERON:0000029	96.30	gold quality
vermiform appendix	UBERON:0001154	93.61	gold quality
granulocyte	CL:0000094	92.38	gold quality
ileal mucosa	UBERON:0000331	91.05	gold quality
blood	UBERON:0000178	90.20	gold quality
apex of heart	UBERON:0002098	89.32	gold quality
caecum	UBERON:0001153	89.27	gold quality
gastrocnemius	UBERON:0001388	88.78	gold quality
bone marrow cell	CL:0002092	87.92	gold quality
gluteal muscle	UBERON:0002000	86.67	gold quality
muscle of leg	UBERON:0001383	86.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.14	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.12	gold quality
middle temporal gyrus	UBERON:0002771	85.35	gold quality
epithelium of nasopharynx	UBERON:0001951	85.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.21	gold quality
tibialis anterior	UBERON:0001385	84.68	silver quality
muscle organ	UBERON:0001630	84.51	gold quality
right frontal lobe	UBERON:0002810	84.47	gold quality
nucleus accumbens	UBERON:0001882	84.00	gold quality
bone marrow	UBERON:0002371	83.68	gold quality
thymus	UBERON:0002370	83.35	gold quality
heart left ventricle	UBERON:0002084	82.81	gold quality
caudate nucleus	UBERON:0001873	82.45	gold quality
cardiac ventricle	UBERON:0002082	82.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.20	gold quality
superficial temporal artery	UBERON:0001614	82.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.74	gold quality
putamen	UBERON:0001874	81.62	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-79	yes	641.65
E-HCAD-4	yes	126.59
E-CURD-122	yes	95.02
E-ANND-3	yes	29.49
E-MTAB-9221	yes	18.66
E-MTAB-9067	yes	12.31
E-CURD-88	yes	4.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting P2RX5, 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-6721-5P	99.93	68.92	2981
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6871-3P	99.43	68.85	741
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-5192	96.89	63.35	879
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722
HSA-MIR-1256	95.44	66.33	784
HSA-MIR-2861	95.24	65.47	1056

Literature-anchored findings (GeneRIF, showing 12)

• Different purinergic receptors have different functional roles in human epidermis with P2Y1 and P2Y2 receptors controlling proliferation, while P2X5 and P2X7 receptors control early differentiation, terminal differentiation and death of keratinocytes. (PMID:12787128)
• Non-melanoma skin cancers express functional purinergic receptors and that P2X7 receptor agonists significantly reduce cell numbers in vitro. (PMID:12880424)
• a P2X5 frameshift mutation has a role in response to treatment of chronic myeloid leukemia (PMID:16322791)
• Increased keratinocyte P2X(5) receptor activity may, in part, be accountable for epidermal thinning in chronic venous insufficiency. (PMID:16967306)
• analysis of topology, helix-helix interactions, and oligomerization of P2X5 subunits (PMID:17001079)
• LRH-1 is aberrantly expressed on solid tumor cells (PMID:18719914)
• These findings provide a rationale for use of LRH-1 as immunotherapeutic target antigen to treat residual or persisting myeloid malignancies after allogeneic stem cell transplantation (PMID:19074734)
• findings indicate that most humans express only a nonfunctional isoform of P2X5, which is in stark contrast to what is seen in other vertebrate species in which P2X5 has been studied, from which only the full-length isoform is known (PMID:20223879)
• Purinergic receptor P2X5 binds to adenosine triphosphate (ATP) to form a molecular complex with ASIC3 (acid-sensing ion channel number 3) to detect muscle ischemia. (PMID:21092862)
• sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns (PMID:24868547)
• The amino acid transporter PAT2 and the purinergic receptor P2RX5 are cell surface markers expressed in classical brown and beige adipocytes. (PMID:25080478)
• These data indicate a functional role of the human P2RX5 splice variant in T cell activation and immunoregulation. (PMID:25181038)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	p2rx5	ENSDARG00000004455
danio_rerio	p2rx8	ENSDARG00000024139
mus_musculus	P2rx5	ENSMUSG00000005950
rattus_norvegicus	P2rx5	ENSRNOG00000019208

Paralogs (6): P2RX7 (ENSG00000089041), P2RX6 (ENSG00000099957), P2RX1 (ENSG00000108405), P2RX3 (ENSG00000109991), P2RX4 (ENSG00000135124), P2RX2 (ENSG00000187848)

Protein

Protein identifiers

P2X purinoceptor 5 — Q93086 (reviewed: Q93086)

Alternative names: ATP receptor, Purinergic receptor

All UniProt accessions (5): Q93086, B4DEG2, H0YHT9, H0YII8, K7EQ78

UniProt curated annotations — full annotation on UniProt →

Function. ATP-gated nonselective transmembrane cation channel permeable to potassium, sodium and calcium. Unlike other P2RX receptors, the P2X5 receptor is also permeable to chloride. May play a supporting role in the inflammatory response. Non-functional.

Subunit / interactions. Functional P2XRs are organized as homomeric and heteromeric trimers. Homotrimer. Forms heterotrimer with P2RX1.

Subcellular location. Cell membrane.

Tissue specificity. Expressed at high levels in brain and immune system.

Activity regulation. Activated by ATP. Slowly desensitizing. Sensitive to the ATP agonist alpha/beta-methylene-ATP.

Domain organisation. The second transmembrane domain and the conserved Asp-355 are essential for P2RX5 subunit assembly.

Polymorphism. A thymine (T) to guanine (G) nucleotide substitution at genomic position chr17:3688012 is very common in human populations. This SNP affects P2RX5 exon 10 splicing resulting in an apparently non-functional protein. This protein lacks the 22 amino acids encoded by exon 10, including parts of the ATP-binding domain and the second transmembrane domain, and is trimerization-defective. The sequence shown in this entry corresponds to the rarer, full length isoform (isoform 6) which is capable of assembling into a functional ATP-gated receptor channel.

Miscellaneous. Due to exon 10 skipping, this isoform is trimerization-defective and therefore unable to assemble into a functional ATP-gated receptor channel.

Similarity. Belongs to the P2X receptor family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q93086-6	6	yes
Q93086-3	1
Q93086-1	2, A
Q93086-2	3, B
Q93086-4	4
Q93086-5	5

RefSeq proteins (8): NP_001191448, NP_001191449, NP_001412011, NP_001412012, NP_001412013, NP_001412014, NP_002552, NP_778255 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001429	P2X_purnocptor	Family
IPR003048	P2X5_purnocptor	Family
IPR027309	P2X_extracellular_dom_sf	Homologous_superfamily
IPR053792	P2X_RECEPTOR_CS	Conserved_site
IPR059116	P2X_receptor	Family

Pfam: PF00864

Catalyzed reactions (Rhea), 3 shown:

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• chloride(in) = chloride(out) (RHEA:29823)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (29 total): sequence conflict 10, disulfide bond 5, splice variant 4, topological domain 3, transmembrane region 2, glycosylation site 2, chain 1, mutagenesis site 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93086-F1	82.23	0.54

Functional residue map

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

Disulfide bonds (5): 129–152, 135–163, 220–229, 263–272, 118–169

Glycosylation sites (2): 77, 202

Mutagenesis-validated functional residues (1):

Position	Phenotype
355	impairs homotrimerization.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-139853	Elevation of cytosolic Ca2+ levels
R-HSA-418346	Platelet homeostasis

MSigDB gene sets: 285 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, GOBP_RESPONSE_TO_ZINC_ION, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_GROWTH, GOBP_BONE_CELL_DEVELOPMENT, GOBP_INORGANIC_ANION_TRANSPORT

GO Biological Process (19): chloride transport (GO:0006821), signal transduction (GO:0007165), nervous system development (GO:0007399), response to pH (GO:0009268), response to zinc ion (GO:0010043), positive regulation of calcium ion transport into cytosol (GO:0010524), response to ATP (GO:0033198), osteoclast maturation (GO:0036179), regulation of skeletal muscle tissue regeneration (GO:0043416), positive regulation of calcium-mediated signaling (GO:0050850), response to calcium ion (GO:0051592), calcium ion transmembrane transport (GO:0070588), positive regulation of calcium ion import across plasma membrane (GO:1905665), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), purinergic nucleotide receptor signaling pathway (GO:0035590), excitatory postsynaptic potential (GO:0060079), monoatomic cation transmembrane transport (GO:0098655), monoatomic anion transmembrane transport (GO:0098656)

GO Molecular Function (11): purinergic nucleotide receptor activity (GO:0001614), transmembrane signaling receptor activity (GO:0004888), extracellularly ATP-gated monoatomic cation channel activity (GO:0004931), monoatomic ion channel activity (GO:0005216), voltage-gated monoatomic ion channel activity (GO:0005244), ATP binding (GO:0005524), ATP-gated ion channel activity (GO:0035381), identical protein binding (GO:0042802), ligand-gated monoatomic anion channel activity (GO:0099095), nucleotide binding (GO:0000166), channel activity (GO:0015267)

GO Cellular Component (4): plasma membrane (GO:0005886), postsynapse (GO:0098794), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Platelet calcium homeostasis	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
monoatomic anion transport	2
response to metal ion	2
positive regulation of calcium ion transmembrane transport	2
monoatomic ion transmembrane transport	2
inorganic anion transport	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
system development	1
response to abiotic stimulus	1
positive regulation of cytosolic calcium ion concentration	1
regulation of calcium ion transport into cytosol	1
calcium ion transport into cytosol	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
osteoclast development	1
cell maturation	1
regulation of response to external stimulus	1
skeletal muscle tissue regeneration	1
regulation of developmental growth	1
regulation of multicellular organismal development	1
calcium-mediated signaling	1
regulation of calcium-mediated signaling	1
positive regulation of intracellular signal transduction	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
positive regulation of calcium ion import	1
calcium ion import across plasma membrane	1
regulation of calcium ion import across plasma membrane	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
cell surface receptor signaling pathway	1
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	1
monoatomic cation transport	1

Protein interactions and networks

STRING

770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
P2RX5	P2RX2	Q9UBL9	948
P2RX5	P2RX3	P56373	868
P2RX5	P2RX1	P51575	816
P2RX5	P2RY2	P41231	804
P2RX5	P2RY4	P51582	803
P2RX5	P2RY11	Q96G91	788
P2RX5	A0A0B4J1V8	A0A0B4J1V8	783
P2RX5	P2RX4	Q99571	775
P2RX5	P2RY6	Q15077	763
P2RX5	P2RY14	Q15391	723
P2RX5	ASIC3	Q9UHC3	723
P2RX5	P2RX6	O15547	713
P2RX5	P2RY13	Q9BPV8	708
P2RX5	P2RY1	P47900	639
P2RX5	SLC36A2	Q495M3	627

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
BORCS8	P2RX5	psi-mi:“MI:0915”(physical association)	0.490
P2RX5	BORCS8	psi-mi:“MI:0915”(physical association)	0.490
P2RX5	TNPO2	psi-mi:“MI:0914”(association)	0.350
P2RX5	thrC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (45): DNAJB9 (Affinity Capture-MS), FAM126A (Affinity Capture-MS), STK17B (Affinity Capture-MS), ITPA (Affinity Capture-MS), ARV1 (Affinity Capture-MS), GALNS (Affinity Capture-MS), TTC17 (Affinity Capture-MS), DPH1 (Affinity Capture-MS), CANX (Affinity Capture-MS), USP30 (Affinity Capture-MS), BRAT1 (Affinity Capture-MS), PBXIP1 (Affinity Capture-MS), TNPO3 (Affinity Capture-MS), PDS5B (Affinity Capture-MS), ADCK1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D3QS97, A1L314, D3YXF5, E7F0Z8, O75339, P02748, P06682, P06683, P07357, P07358, P10643, P10820, P35763, P48747, P48770, P51578, P55314, P79755, P98136, P98137, Q2KJC3, Q2M385, Q3MHN2, Q3V5L5, Q5RBP9, Q62930, Q64663, Q66K08, Q66S13, Q66S17, Q66S21, Q66S25, Q6UX71, Q765H6, Q8BG22, Q8BH35, Q8K182, Q8L612, Q8N2E2, Q90X85

Diamond homologs: F8W463, O15547, O54803, O70397, P47824, P49653, P49654, P51575, P51576, P51577, P51578, P51579, P56373, Q3UR32, Q5E9U1, Q64663, Q8K3P1, Q91VE2, Q93086, Q99571, Q99572, Q9JJX6, Q9UBL9, Q9Z1M0, Q86JM7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	79
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2422206	NC_000017.10:g.(?3379454)(3819519_?)del	Pathogenic

SpliceAI

2275 predictions. Top by Δscore:

Variant	Effect	Δscore
17:3681902:T:TA	donor_gain	1.0000
17:3685512:C:CA	donor_gain	1.0000
17:3688009:CACC:C	donor_loss	1.0000
17:3688010:A:T	donor_loss	1.0000
17:3688011:CCTTG:C	donor_gain	1.0000
17:3689643:C:CT	acceptor_gain	1.0000
17:3690068:A:AC	donor_gain	1.0000
17:3690069:C:CC	donor_gain	1.0000
17:3690425:A:AC	donor_gain	1.0000
17:3690426:C:CC	donor_gain	1.0000
17:3690426:CT:C	donor_gain	1.0000
17:3691640:AGAC:A	donor_gain	1.0000
17:3691790:CCCAT:C	acceptor_gain	1.0000
17:3691791:CCAT:C	acceptor_gain	1.0000
17:3691791:CCATC:C	acceptor_gain	1.0000
17:3691792:CAT:C	acceptor_gain	1.0000
17:3691792:CATC:C	acceptor_gain	1.0000
17:3691793:ATCT:A	acceptor_loss	1.0000
17:3691794:TC:T	acceptor_loss	1.0000
17:3691794:TCTG:T	acceptor_loss	1.0000
17:3691795:C:CC	acceptor_gain	1.0000
17:3695862:AACTT:A	donor_loss	1.0000
17:3695863:ACTT:A	donor_loss	1.0000
17:3695863:ACTTA:A	donor_loss	1.0000
17:3695864:CTTAC:C	donor_loss	1.0000
17:3695865:TTACA:T	donor_loss	1.0000
17:3695866:TA:T	donor_loss	1.0000
17:3695867:A:AC	donor_gain	1.0000
17:3695868:C:CT	donor_gain	1.0000
17:3695868:CA:C	donor_gain	1.0000

AlphaMissense

2778 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:3688730:C:A	W261C	1.000
17:3688730:C:G	W261C	1.000
17:3688732:A:G	W261R	1.000
17:3688732:A:T	W261R	1.000
17:3688725:C:G	C263S	0.999
17:3688726:A:T	C263S	0.999
17:3690091:A:G	F198S	0.999
17:3690456:C:A	W168C	0.999
17:3690456:C:G	W168C	0.999
17:3690637:C:G	C135S	0.999
17:3690638:A:T	C135S	0.999
17:3688064:C:G	R310P	0.998
17:3688065:G:T	R310S	0.998
17:3688698:C:G	C272S	0.998
17:3688699:A:G	C272R	0.998
17:3688699:A:T	C272S	0.998
17:3688724:A:C	C263W	0.998
17:3688725:C:T	C263Y	0.998
17:3688731:C:G	W261S	0.998
17:3690090:G:C	F198L	0.998
17:3690090:G:T	F198L	0.998
17:3690091:A:C	F198C	0.998
17:3690092:A:G	F198L	0.998
17:3690458:A:G	W168R	0.998
17:3690458:A:T	W168R	0.998
17:3690505:C:G	C152S	0.998
17:3690506:A:T	C152S	0.998
17:3688725:C:A	C263F	0.997
17:3688726:A:G	C263R	0.997
17:3690081:G:C	F201L	0.997

dbSNP variants (sampled 300 via entrez): RS1000075365 (17:3697247 C>T), RS1000312763 (17:3685377 C>T), RS1000343690 (17:3675772 C>T), RS1000376237 (17:3675329 C>A,G,T), RS1000587742 (17:3681485 C>A,T), RS1000644158 (17:3681362 C>T), RS1000942879 (17:3696868 T>G), RS1001002859 (17:3684642 G>A), RS1001116941 (17:3684426 A>G), RS1001241085 (17:3679495 G>C), RS1001344935 (17:3674499 C>T), RS1001375917 (17:3674224 T>C,G), RS1001780875 (17:3672762 T>C), RS1001996851 (17:3683683 T>A), RS1002281795 (17:3678143 G>A)

Disease associations

OMIM: gene MIM:602836 | disease phenotypes: MIM:271900

GenCC curated gene-disease

Mondo (1): Canavan disease (MONDO:0010079)

Orphanet (1): Canavan disease (Orphanet:141)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D017825	Canavan Disease	C10.228.140.163.100.362.375; C10.228.140.695.625.375; C10.314.400.375; C10.574.500.300; C16.320.400.150; C16.320.565.189.362.375; C18.452.132.100.362.375; C18.452.648.189.362.375

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4524012 (PROTEIN FAMILY), CHEMBL4942 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 36,848 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL265502	SURAMIN	3	36,848

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: lgic — P2X receptors

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
ATP	Agonist	6.0	pEC50
suramin	Antagonist	5.4	pIC50

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.78	IC50	1651	nM	CHEMBL5208562
5.15	IC50	7010	nM	CHEMBL1615626
5.07	IC50	8450	nM	CHEMBL69234
5.04	IC50	9037	nM	CHEMBL5172961

PubChem BioAssay actives

4 with measured affinity, of 53 total; 4 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
N-[(4-nitrophenyl)carbamothioyl]-1,3-benzodioxole-5-carboxamide	1884359: Antagonist activity against human P2X5R stably transfected in human 1321N1 cells incubated for 30 mins by Fura-2 AM staining based calcium influx assay	ic50	1.6510	uM
4-[[3-formyl-4-hydroxy-5-methyl-2-(phosphonooxymethyl)phenyl]diazenyl]benzene-1,3-disulfonic acid	1879234: Antagonist activity at human P2X5 receptor expressed in human 1321N1 cells assessed as reduction in intracellular Ca2+ influx incubated for 30 mins by Fura-2 AM based fluorescence assay	ic50	7.0100	uM
4-[[4-formyl-5-hydroxy-6-methyl-3-(phosphonooxymethyl)-2-pyridinyl]diazenyl]benzene-1,3-disulfonic acid	1884359: Antagonist activity against human P2X5R stably transfected in human 1321N1 cells incubated for 30 mins by Fura-2 AM staining based calcium influx assay	ic50	8.4500	uM
N-[(2-bromo-4-methylphenyl)carbamothioyl]adamantane-1-carboxamide	1879234: Antagonist activity at human P2X5 receptor expressed in human 1321N1 cells assessed as reduction in intracellular Ca2+ influx incubated for 30 mins by Fura-2 AM based fluorescence assay	ic50	9.0370	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	4
Cyclosporine	increases expression, decreases expression	4
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Cisplatin	decreases expression, affects cotreatment	1
Copper	affects binding, decreases expression	1
Demecolcine	decreases expression	1
Doxorubicin	affects expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1

ChEMBL screening assays

13 unique, capped per target: 10 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4339641	Binding	Negative allosteric modulation of human P2X expressed in Xenopus laevis oocytes assessed as inhibition of ATP-induced current response at 30 uM at -40 mV holding potential by two-electrode voltage clamp method relative to ATP alone	Di-aryl Sulfonamide Motif Adds π-Stacking Bulk in Negative Allosteric Modulators of the NMDA Receptor. — ACS Med Chem Lett
CHEMBL1017980	Functional	Antagonist activity at P2X5 receptor up to 10 uM	Identification and SAR of novel diaminopyrimidines. Part 2: The discovery of RO-51, a potent and selective, dual P2X(3)/P2X(2/3) antagonist for the treatment of pain. — Bioorg Med Chem Lett

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1ZQ	Abcam HeLa P2RX5 KO	Cancer cell line	Female
CVCL_D7WE	Ubigene A-549 P2RX5 KO	Cancer cell line	Male
CVCL_D8RX	Ubigene HCT 116 P2RX5 KO	Cancer cell line	Male
CVCL_D9M2	Ubigene HEK293 P2RX5 KO	Transformed cell line	Female
CVCL_E0JN	Ubigene HeLa P2RX5 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00657748	PHASE2	WITHDRAWN	Lithium and Acetate for Canavan Disease
NCT04833907	PHASE1/PHASE2	ENROLLING_BY_INVITATION	rAAV-Olig001-ASPA Gene Therapy for Treatment of Children With Typical Canavan Disease
NCT04998396	PHASE1/PHASE2	RECRUITING	A Study of AAV9 Gene Therapy in Participants With Canavan Disease (CANaspire Clinical Trial)
NCT00724802	Not specified	UNKNOWN	Oral Glyceryl Triacetate (GTA) in Newborns With Canavan
NCT01999257	Not specified	COMPLETED	Efficacy Study of an Online Educational Module Before Carrier Genetic Screening in Persons of Ashkenazi Jewish Descent.
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT02851563	Not specified	COMPLETED	A Natural History Study of Canavan Disease
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04126005	Not specified	COMPLETED	Natural History Study of Patients With Canavan Disease (CANinform Study)
NCT05317780	Not specified	NO_LONGER_AVAILABLE	Canavan-Single Patient IND