PRPS1

Summary

PRPS1 (phosphoribosyl pyrophosphate synthetase 1, HGNC:9462) is a protein-coding gene on chromosome Xq22.3, encoding Ribose-phosphate pyrophosphokinase 1 (P60891). Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis. In precision oncology, PRPS1 A190T confers sensitivity to Mercaptopurine + Lometrexol in B-lymphoblastic Leukemia/lymphoma (CIViC Level D); 26 further curated variant–drug associations are listed below.

This gene encodes an enzyme that catalyzes the phosphoribosylation of ribose 5-phosphate to 5-phosphoribosyl-1-pyrophosphate, which is necessary for purine metabolism and nucleotide biosynthesis. Defects in this gene are a cause of phosphoribosylpyrophosphate synthetase superactivity, Charcot-Marie-Tooth disease X-linked recessive type 5 and Arts Syndrome. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5631 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PRPS1 deficiency disorder (Definitive, ClinGen) — +8 more curated relationships
• Clinical variants (ClinVar): 430 total — 20 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 144
• Druggable target: yes
• Precision-oncology evidence (CIViC): 27 curated variant–drug associations
• MANE Select transcript: NM_002764

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9462
Approved symbol	PRPS1
Name	phosphoribosyl pyrophosphate synthetase 1
Location	Xq22.3
Locus type	gene with protein product
Status	Approved
Aliases	CMTX5, DFNX1, PRS-I, PPRibP
Ensembl gene	ENSG00000147224
Ensembl biotype	protein_coding
OMIM	311850
Entrez	5631

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 12 nonsense_mediated_decay, 10 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000372418, ENST00000372419, ENST00000372428, ENST00000372435, ENST00000643795, ENST00000644642, ENST00000645638, ENST00000645903, ENST00000646815, ENST00000674525, ENST00000674826, ENST00000674843, ENST00000675046, ENST00000675082, ENST00000675124, ENST00000675263, ENST00000675304, ENST00000675353, ENST00000675630, ENST00000675720, ENST00000675875, ENST00000675921, ENST00000676092, ENST00000676322, ENST00000676365

RefSeq mRNA: 2 — MANE Select: NM_002764 NM_001204402, NM_002764

CCDS: CCDS14529

Canonical transcript exons

ENST00000372435 — 7 exons

Exon	Start	End
ENSE00001201218	107647606	107647765
ENSE00001201231	107642366	107642490
ENSE00001457786	107649940	107651026
ENSE00001668533	107640902	107641000
ENSE00001947916	107628510	107628750
ENSE00003503964	107639295	107639478
ENSE00003711527	107645177	107645350

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 96.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.4984 / max 4077.4024, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197178	49.4984	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	96.76	gold quality
ventricular zone	UBERON:0003053	96.61	gold quality
sural nerve	UBERON:0015488	95.23	gold quality
hypothalamus	UBERON:0001898	94.55	gold quality
cortical plate	UBERON:0005343	94.38	gold quality
ganglionic eminence	UBERON:0004023	94.36	gold quality
prefrontal cortex	UBERON:0000451	94.26	gold quality
adenohypophysis	UBERON:0002196	94.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.91	gold quality
stromal cell of endometrium	CL:0002255	93.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.64	gold quality
cerebellar hemisphere	UBERON:0002245	93.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.56	gold quality
cerebellar cortex	UBERON:0002129	93.54	gold quality
right lobe of liver	UBERON:0001114	93.52	gold quality
left ovary	UBERON:0002119	93.42	gold quality
type B pancreatic cell	CL:0000169	93.41	gold quality
bone marrow cell	CL:0002092	93.35	gold quality
gastrocnemius	UBERON:0001388	93.32	gold quality
colonic epithelium	UBERON:0000397	93.31	gold quality
muscle of leg	UBERON:0001383	93.30	gold quality
lymph node	UBERON:0000029	93.27	gold quality
bone marrow	UBERON:0002371	93.25	gold quality
pituitary gland	UBERON:0000007	93.24	gold quality
embryo	UBERON:0000922	93.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.23	gold quality
cingulate cortex	UBERON:0003027	93.20	gold quality
left lobe of thyroid gland	UBERON:0001120	93.19	gold quality
right ovary	UBERON:0002118	93.18	gold quality
right frontal lobe	UBERON:0002810	93.14	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	517.97
E-ANND-3	yes	5.04
E-MTAB-6142	no	392.17

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, PPARG

miRNA regulators (miRDB)

61 targeting PRPS1, 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-8485	100.00	77.57	4731
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-9-3P	99.96	70.88	2068
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-651-3P	99.94	73.48	5177
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-6165	99.44	67.12	1389

Literature-anchored findings (GeneRIF, showing 40)

• Refinements were made on the DFN2 locus on the X chromosome. (PMID:15240907)
• p300 may play a role in the regulation of DNA synthesis through interactions with PRS1 (PMID:15943588)
• PRS1 belongs to space group R3, with unit-cell parameters a=b=168.846, c=61.857 A, assuming two molecules in asymmetric unit & volume-to-weight ratio of 2.4 angstroms3 Da(-1), which was consistent with result calculated from self-rotation function. (PMID:16682768)
• new SO4(2-)-binding site is a second allosteric site to regulate the enzymatic activity (PMID:16939420)
• Linkage analysis in a Dutch family and an Australian family suggested that the candidate gene for Arts syndrome is PRPS1, which maps to Xq22.1-q24. (PMID:17701896)
• Missense mutations were identified at conserved amino acids in the PRPS1 gene on Xq22.3 in two families with a syndromic form of inherited peripheral neuropathy, one of Asian and one of European descent. (PMID:17701900)
• increased activity of this gene leads to gout (PMID:18409517)
• The N114S mutation alters the secondary structure of PRS1;the structural alteration caused by the N114S mutation influences the conformation of the ATP-binding loop and leads to the loss of ATP-induced aggregation. (PMID:19161981)
• PRPS1 loss of function mutations cause a type of nonsyndromic X-linked sensorineural deafness, DFN2 (PMID:20021999)
• PRPS1 mutations; neurological phenotype in all four PRPS1-related disorders seems to result primarily from reduced levels of GTP & possibly other purine nucleotides including ATP, suggesting these disorders belong to the same disease spectrum [review] (PMID:20380929)
• In four hyperuricemic patients with mild neurological abnormality, molecular analysis of PRPS1 was performed , but no mutations in PRPP synthetase were found. (PMID:20544509)
• Translocation of ARTS initiates a first wave of caspase activation leading to the subsequent release of additional mitochondrial factors, including cytochrome C and SMAC/Diablo. (PMID:21869827)
• Three HPRT1 mutations in Lesch-Nyhan families were identified but no mutation was identified in any patient in the analysis of PRPS1. (PMID:22132986)
• missense mutations in PRPS1 can cause a continuous spectrum of features ranging from progressive non-syndromic postlingual hearing impairment to uric acid overproduction, and recurrent infections depending on the functional sites that are affected (PMID:22246954)
• Review: discuss role of PRPS1 mutations in hearing loss. (PMID:23190330)
• The crystal structure of the ADP-binding pocket of the PRPS1 D52H-mutant and evidence of reduced inhibitor sensitivity. (PMID:23509005)
• respective phenotypic presentation seems to be determined by the exact PRPS1 mutation and the residual enzyme activity, the latter being largely influenced by the degree of skewed X-inactivation (PMID:24528855)
• Females with a missense mutation in PRPS1, exhibit neuropathy, hearing loss and retinopathy. (PMID:25491489)
• analysis of intrafamilial phenotypic variation associated with a single PRPS1 mutation in syndromic or nonsyndromic hearing impairment (PMID:25785835)
• Study identified the critical region in the ARTS promoter and demonstrated that the Sp1 transcription factor could regulate the activity of the ARTS promoter through multiple Sp1 binding sites. (PMID:25790304)
• The expression of different genes encoding subunits of PRPS enzyme is affected by hypoxia in tumor glioma cells, but the effect of hypoxia is modified by suppression of endoplasmic reticulum stress signaling enzyme ERN1. (PMID:25816608)
• the de novo purine synthesis inhibitor lometrexol effectively abrogated PRPS1 mutant-driven drug resistance. (PMID:25962120)
• evaluation of current literature on PRPS1-related syndromes and summaries of potential therapies [review] (PMID:26089585)
• CRC cells that overexpressed miR124 or with knockdown of RPIA or PRPS1 had reduced DNA synthesis and proliferation, whereas cells incubated with an inhibitor of miR124 had significantly increased DNA synthesis and proliferation and formed more colonies. (PMID:26248089)
• A novel PRPS1 mutation related to early-onset progressive nonsyndromic hearing loss. (PMID:27886419)
• High PRPS1 expression is associated with chemoresistance in breast cancer. (PMID:28177767)
• This report highlights the unexpected finding of retinal degeneration in females caused by missense variants in the X-linked gene PRPS1 and expands our understanding of the phenotypic outcome of specific variants. (PMID:28967191)
• ARTS binds directly to both XIAP and Bcl-2. ARTS functions as a distinct Bcl-2 antagonist by binding and leading to its degradation. (PMID:29020630)
• suggests that the four mutations might affect the PRPS1 protein function and stability of the structure (PMID:29047041)
• Our study not only provides mechanistic rationale for re-targeting drug resistant cells in acute lymphoblastic leukemia (ALL), but also implicates that ALL patients who harbor relapse-specific mutations of PRPS1 might benefit from 5-FU-based chemotherapy in clinical settings. (PMID:30255549)
• PRPS1 protein and transcript levels are detected as significantly decreased in cell lines derived from the Hutchinson-Gilford progeria syndrome patients. (PMID:30379953)
• High PRPS1 expression is associated with colorectal cancer. (PMID:31253668)
• CMTX5 is probably under-diagnosed, as an overlap among the different features due to PRPS1 exists. Patients who developed polyneuropathy associated to sensorineural deafness and optic atrophy during childhood should be assessed for (PMID:31338985)
• A novel mutation in gene of PRPS1 in a young Chinese woman with X-linked gout: a case report and review of the literature. (PMID:31773495)
• Molecular mechanism of c-Myc and PRPS1/2 against thiopurine resistance in Burkitt’s lymphoma. (PMID:32391636)
• PRPS1 loss-of-function variants, from isolated hearing loss to severe congenital encephalopathy: New cases and literature review. (PMID:32781272)
• SNHG16 knockdown inhibits tumorigenicity of neuroblastoma in children via miR-15b-5p/PRPS1 axis. (PMID:33105440)
• PRPS1-mediated purine biosynthesis is critical for pluripotent stem cell survival and stemness. (PMID:33493137)
• NUDT15 polymorphism and NT5C2 and PRPS1 mutations influence thiopurine sensitivity in acute lymphoblastic leukaemia cells. (PMID:34636169)
• Circular RNA circKIF2A Contributes to the Progression of Neuroblastoma Through Regulating PRPS1 Expression by Sponging miR-377-3p. (PMID:35039981)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prps1a	ENSDARG00000015524
danio_rerio	prps1b	ENSDARG00000037506
mus_musculus	Prps1	ENSMUSG00000031432
drosophila_melanogaster	Prps	FBGN0036030
caenorhabditis_elegans		WBGENE00020107

Paralogs (4): PRPS2 (ENSG00000101911), PRPSAP2 (ENSG00000141127), PRPSAP1 (ENSG00000161542), PRPS1L1 (ENSG00000229937)

Protein

Protein identifiers

Ribose-phosphate pyrophosphokinase 1 — P60891 (reviewed: P60891)

Alternative names: PPRibP, Phosphoribosyl pyrophosphate synthase I

All UniProt accessions (18): P60891, A0A0A0MRQ9, A0A2R8Y7H4, A0A6Q8PEU0, A0A6Q8PFD1, A0A6Q8PFD7, A0A6Q8PG13, A0A6Q8PG31, A0A6Q8PG33, A0A6Q8PG82, A0A6Q8PGF9, A0A6Q8PGP2, A0A6Q8PGX9, A0A6Q8PHI4, A0A6Q8PHK9, B1ALA7, B1ALA9, Q15244

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.

Subunit / interactions. Homodimer. The active form is probably a hexamer composed of 3 homodimers.

Disease relevance. Phosphoribosyl pyrophosphate synthetase I deficiency is a rare condition caused by mutations in PRPS1 that lead to variable disease phenotypes including optic atrophy, retinitis pigmentosa, ataxia, peripheral neuropathy and hearing loss. Phosphoribosylpyrophosphate synthetase superactivity (PRPS1 superactivity) [MIM:300661] Familial disorder characterized by excessive purine production, gout and uric acid urolithiasis. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, X-linked recessive, 5 (CMTX5) [MIM:311070] A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies characterized by severely reduced motor nerve conduction velocities (NCVs) (less than 38m/s) and segmental demyelination and remyelination, and primary peripheral axonal neuropathies characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy. The disease is caused by variants affecting the gene represented in this entry. ARTS syndrome (ARTS) [MIM:301835] A disorder characterized by intellectual disability, early-onset hypotonia, ataxia, delayed motor development, hearing impairment, and optic atrophy. Susceptibility to infections, especially of the upper respiratory tract, can result in early death. The disease is caused by variants affecting the gene represented in this entry. Deafness, X-linked, 1 (DFNX1) [MIM:304500] A form of deafness characterized by progressive, severe-to-profound sensorineural hearing loss in males. Females manifest mild to moderate hearing loss. The disease is caused by variants affecting the gene represented in this entry. A mutation in PRPS1 has been found in a patient with a phenotype that bridges that of PRSPS1 superactivity and ARTS syndrome with uric acid overproduction without gout but with recurrent infections, sensorineural hearing loss and motor neuropathy. The intermediate phenotype may be because Leu-142 variant affects both allosteric sites that are involved in inhibition of PRPS1 and the ATP-binding site, which suggests that this substitution can result both in a gain-of-function and loss-of-function of PRPP synthetase.

Activity regulation. Activated by magnesium and inorganic phosphate. Inhibited by ADP and GDP.

Pathway. Metabolic intermediate biosynthesis; 5-phospho-alpha-D-ribose 1-diphosphate biosynthesis; 5-phospho-alpha-D-ribose 1-diphosphate from D-ribose 5-phosphate (route I): step 1/1.

Similarity. Belongs to the ribose-phosphate pyrophosphokinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P60891-1	1	yes
P60891-2	2

RefSeq proteins (2): NP_001191331, NP_002755* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000836	PRTase_dom	Domain
IPR000842	PRib_PP_synth_CS	Conserved_site
IPR005946	Rib-P_diPkinase	Family
IPR029057	PRTase-like	Homologous_superfamily
IPR029099	Pribosyltran_N	Domain
IPR037515	Rib-P_diPkinase_bac	Family

Pfam: PF13793, PF14572

Enzyme classification (BRENDA):

• EC 2.7.6.1 — ribose-phosphate diphosphokinase (BRENDA: 29 organisms, 91 substrates, 164 inhibitors, 160 Km, 17 kcat entries)

Substrate kinetics (BRENDA)

21 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.007–2.9	66
D-RIBOSE 5-PHOSPHATE	0.0082–2.8	40
AMP	0.117–0.32	8
MG2+	0.0002–1.5	8
PHOSPHATE	0.008–40	5
9-(2-PHOSPHONYLMETHOXYETHOXY)ADENINE	0.308–0.789	4
9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE	0.656–1.47	4
2’,3’-DIDEOXY-2’,3’-DIDEHYDRO-ADENOSINE-5’-MONOP	0.317–0.377	3
5-PHOSPHO-ALPHA-D-RIBOSE 1-DIPHOSPHATE	0.0289–0.0418	3
(R)9-(2-PHOSPHONYLMETHOXYPROPYL)ADENINE	1.29–3.571	2
(R)9-(3-FLUORO-2-PHOSPHONYLMETHOXYPROPYL)ADENINE	1.14–1.923	2
(S)9-(2-PHOSPHONYLMETHOXYPROPYL)ADENINE	1.54–2.174	2
(S)9-(3-FLUORO-2-PHOSPHONYLMETHOXYPROPYL)ADENINE	0.575–3.636	2
5-PHOSPHO-D-RIBOSE DIPHOSPHATE	0.29	2
RIBOSE 5-PHOSPHATE	0.033	2

Catalyzed reactions (Rhea), 1 shown:

• D-ribose 5-phosphate + ATP = 5-phospho-alpha-D-ribose 1-diphosphate + AMP + H(+) (RHEA:15609)

UniProt features (69 total): sequence variant 19, strand 17, helix 12, binding site 6, mutagenesis site 5, sequence conflict 3, turn 3, initiator methionine 1, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

27 structures.

PDB	Method	Resolution (Å)
8DBI	ELECTRON MICROSCOPY	2
8DBJ	ELECTRON MICROSCOPY	2
3S5J	X-RAY DIFFRACTION	2.02
8DBE	ELECTRON MICROSCOPY	2.1
8DBK	ELECTRON MICROSCOPY	2.1
4M0P	X-RAY DIFFRACTION	2.11
4LZN	X-RAY DIFFRACTION	2.14
2H06	X-RAY DIFFRACTION	2.2
2H07	X-RAY DIFFRACTION	2.2
2HCR	X-RAY DIFFRACTION	2.2
8DBF	ELECTRON MICROSCOPY	2.2
8DBG	ELECTRON MICROSCOPY	2.2
8DBH	ELECTRON MICROSCOPY	2.2
4F8E	X-RAY DIFFRACTION	2.27
8DBL	ELECTRON MICROSCOPY	2.4
8DBM	ELECTRON MICROSCOPY	2.4
8DBN	ELECTRON MICROSCOPY	2.4
2H08	X-RAY DIFFRACTION	2.5
8DBO	ELECTRON MICROSCOPY	2.5
3EFH	X-RAY DIFFRACTION	2.6
4M0U	X-RAY DIFFRACTION	2.74
4LYG	X-RAY DIFFRACTION	3
8YPZ	X-RAY DIFFRACTION	3
8YQ0	X-RAY DIFFRACTION	3.1
8DBC	ELECTRON MICROSCOPY	3.2
8DBD	ELECTRON MICROSCOPY	3.2
4LZO	X-RAY DIFFRACTION	3.31

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60891-F1	94.77	0.90

Functional residue map

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

Ligand- & substrate-binding residues (6): 96–101; 128; 130; 130; 139; 143

Mutagenesis-validated functional residues (5):

Position	Phenotype
132	reduces catalytic activity.
132	no effect on catalytic activity.
144	no effect on catalytic activity.
146	no effect on catalytic activity.
146	reduces catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-73843	5-Phosphoribose 1-diphosphate biosynthesis

MSigDB gene sets: 520 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, E2F_Q4, MULLIGHAN_NPM1_SIGNATURE_3_UP, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, HARRIS_HYPOXIA, E2F4DP1_01, MODULE_56, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, PUJANA_CHEK2_PCC_NETWORK, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GTGCCTT_MIR506

GO Biological Process (10): 5-phosphoribose 1-diphosphate biosynthetic process (GO:0006015), purine nucleobase metabolic process (GO:0006144), purine nucleotide biosynthetic process (GO:0006164), pyrimidine nucleotide biosynthetic process (GO:0006221), nervous system development (GO:0007399), ribonucleoside monophosphate biosynthetic process (GO:0009156), urate biosynthetic process (GO:0034418), hypoxanthine biosynthetic process (GO:0046101), nucleobase-containing compound metabolic process (GO:0006139), nucleotide biosynthetic process (GO:0009165)

GO Molecular Function (10): magnesium ion binding (GO:0000287), ribose phosphate diphosphokinase activity (GO:0004749), ATP binding (GO:0005524), kinase activity (GO:0016301), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (4): ribose phosphate diphosphokinase complex (GO:0002189), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Pentose phosphate pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nucleotide biosynthetic process	2
purine-containing compound biosynthetic process	2
ribose phosphate biosynthetic process	1
5-phosphoribose 1-diphosphate metabolic process	1
nucleobase metabolic process	1
purine-containing compound metabolic process	1
purine nucleotide metabolic process	1
pyrimidine nucleotide metabolic process	1
pyrimidine-containing compound biosynthetic process	1
system development	1
nucleoside monophosphate biosynthetic process	1
small molecule biosynthetic process	1
urate metabolic process	1
purine nucleobase biosynthetic process	1
hypoxanthine metabolic process	1
primary metabolic process	1
nucleotide metabolic process	1
nucleoside phosphate biosynthetic process	1
metal ion binding	1
diphosphotransferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transferase activity, transferring phosphorus-containing groups	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
cation binding	1
transferase complex, transferring phosphorus-containing groups	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

564 interactions, top by confidence:

A	B	Type	Score
PRPS1	PRPSAP1	psi-mi:“MI:0915”(physical association)	0.940
PRPSAP1	PRPS1	psi-mi:“MI:0915”(physical association)	0.940
PRPS1	PRPS2	psi-mi:“MI:0915”(physical association)	0.900
PRPS2	PRPS1	psi-mi:“MI:0915”(physical association)	0.900
PRPS1	PRPS1	psi-mi:“MI:0915”(physical association)	0.900
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
PRPSAP2	PRPS1	psi-mi:“MI:0915”(physical association)	0.840
SPG21	PRPS1	psi-mi:“MI:0915”(physical association)	0.830
PRPS1	SPG21	psi-mi:“MI:0915”(physical association)	0.830

BioGRID (317): PRPS1 (Two-hybrid), PRPS2 (Two-hybrid), PRPSAP1 (Two-hybrid), SPG21 (Two-hybrid), PRPS1 (Affinity Capture-MS), EML4 (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), PRPSAP1 (Affinity Capture-MS), PRPSAP2 (Affinity Capture-MS), NMT2 (Affinity Capture-MS), NDUFB9 (Affinity Capture-MS), PRPS1L1 (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-MS), NFRKB (Affinity Capture-MS), ELP3 (Affinity Capture-MS)

ESM2 similar proteins: B9KPJ0, O94413, P09330, P11908, P21108, P38063, P38620, P38689, P46585, P60891, P60892, P65234, P65235, P65239, P65240, Q1LTH2, Q2HJ58, Q4R4R7, Q4R4U3, Q54PA9, Q55848, Q5R8F8, Q5RFJ7, Q5XGI0, Q5ZI49, Q7MT83, Q7NQS9, Q7U7L5, Q7UPM4, Q7VFY9, Q7ZXC9, Q82TQ4, Q83AQ1, Q87A22, Q88VA5, Q8DWM2, Q8FZF0, Q8K9X2, Q8KCQ2, Q8PC63

Diamond homologs: A2VDS0, A6W1C7, O08618, O33924, O60256, O67556, O94413, P09330, P0A1V6, P0A1V7, P0A717, P0A718, P0A719, P11908, P14193, P21108, P32895, P38063, P38620, P38689, P41831, P42816, P44328, P46585, P56184, P57266, P60891, P60892, P65234, P65235, P65236, P65237, P65238, P65239, P65240, P87171, Q08DW2, Q14558, Q1LTH2, Q28DH0

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
PRKAA1	“down-regulates activity”	PRPS1	phosphorylation
AMPK	“down-regulates activity”	PRPS1	phosphorylation
PRPS1	up-regulates	Nucleotide_synthesis
PRPS1	“down-regulates quantity”	“D-ribofuranose 5-phosphate(2-)”	“chemical modification”
PRPS1	“up-regulates quantity”	“5-phospho-α-D-ribose 1-diphosphate”	“chemical modification”
CDK1	“up-regulates activity”	PRPS1	phosphorylation
KHK	“up-regulates activity”	PRPS1	phosphorylation
ADP	“down-regulates activity”	PRPS1	“chemical inhibition”
AMP	“down-regulates activity”	PRPS1	“chemical inhibition”
GDP	“down-regulates activity”	PRPS1	“chemical inhibition”
LATS2	“down-regulates quantity by destabilization”	PRPS1	phosphorylation
LATS1	“down-regulates quantity by destabilization”	PRPS1	phosphorylation
TBK1	“up-regulates activity”	PRPS1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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
FCGR3A-mediated phagocytosis	10	16.1×	2e-07
Parasite infection	5	14.9×	1e-03
Leishmania phagocytosis	5	14.9×	1e-03
RHOU GTPase cycle	6	14.4×	4e-04
EPHB-mediated forward signaling	6	13.7×	4e-04
RHO GTPases Activate WASPs and WAVEs	5	13.7×	1e-03
VEGFA-VEGFR2 Pathway	11	13.2×	2e-07
Regulation of actin dynamics for phagocytic cup formation	8	12.7×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
Fc-gamma receptor signaling pathway involved in phagocytosis	5	24.7×	2e-03
positive regulation of actin filament polymerization	6	14.0×	2e-03
ephrin receptor signaling pathway	5	12.1×	8e-03
JNK cascade	6	11.5×	3e-03
response to hypoxia	9	6.1×	3e-03
intracellular signal transduction	15	4.0×	2e-03
negative regulation of apoptotic process	15	3.7×	3e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	20
Uncertain significance	121
Likely benign	149
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100767	NM_002764.4(PRPS1):c.362C>G (p.Ala121Gly)	Pathogenic
1208551	NM_002764.4(PRPS1):c.250C>T (p.Arg84Trp)	Pathogenic
140571	NM_002764.4(PRPS1):c.337G>T (p.Ala113Ser)	Pathogenic
140573	NM_002764.4(PRPS1):c.925G>T (p.Val309Phe)	Pathogenic
1454019	NM_002764.4(PRPS1):c.621del (p.Val208fs)	Pathogenic
2004009	NM_002764.4(PRPS1):c.462G>A (p.Trp154Ter)	Pathogenic
2122144	NM_002764.4(PRPS1):c.570del (p.Ala190_Leu191insTer)	Pathogenic
223100	NM_002764.4(PRPS1):c.830A>C (p.Gln277Pro)	Pathogenic
223101	NM_002764.4(PRPS1):c.46T>C (p.Ser16Pro)	Pathogenic
2756259	NM_002764.4(PRPS1):c.506C>T (p.Ser169Leu)	Pathogenic
29989	NM_002764.4(PRPS1):c.424G>C (p.Val142Leu)	Pathogenic
520913	NM_002764.4(PRPS1):c.307-2A>G	Pathogenic
9930	NM_002764.4(PRPS1):c.154G>C (p.Asp52His)	Pathogenic
9931	NM_002764.4(PRPS1):c.385C>A (p.Leu129Ile)	Pathogenic
9932	NM_002764.4(PRPS1):c.569C>T (p.Ala190Val)	Pathogenic
9933	NM_002764.4(PRPS1):c.579C>G (p.His193Gln)	Pathogenic
9934	NM_002764.4(PRPS1):c.129A>C (p.Glu43Asp)	Pathogenic
9937	NM_002764.4(PRPS1):c.398A>C (p.Gln133Pro)	Pathogenic
9938	NM_002764.4(PRPS1):c.193G>A (p.Asp65Asn)	Pathogenic
9941	NM_002764.4(PRPS1):c.869T>C (p.Ile290Thr)	Pathogenic
1685417	NM_002764.4(PRPS1):c.127G>A (p.Glu43Lys)	Likely pathogenic
1710220	NM_002764.4(PRPS1):c.826C>T (p.Pro276Ser)	Likely pathogenic
245728	NM_002764.4(PRPS1):c.319A>G (p.Ile107Val)	Likely pathogenic
245839	NM_002764.4(PRPS1):c.361G>A (p.Ala121Thr)	Likely pathogenic
2673251	NM_002764.4(PRPS1):c.74T>C (p.Leu25Pro)	Likely pathogenic
3066161	NM_002764.4(PRPS1):c.575T>A (p.Ile192Asn)	Likely pathogenic
3601703	NM_002764.4(PRPS1):c.826C>G (p.Pro276Ala)	Likely pathogenic
3601704	NM_002764.4(PRPS1):c.838A>G (p.Lys280Glu)	Likely pathogenic
3724576	NM_002764.4(PRPS1):c.122+1G>A	Likely pathogenic
446161	NM_002764.4(PRPS1):c.47C>T (p.Ser16Phe)	Likely pathogenic

SpliceAI

1011 predictions. Top by Δscore:

Variant	Effect	Δscore
X:107628748:CTGGT:C	donor_loss	1.0000
X:107628749:TGG:T	donor_loss	1.0000
X:107628751:G:GG	donor_gain	1.0000
X:107628751:GTA:G	donor_loss	1.0000
X:107628752:T:A	donor_loss	1.0000
X:107639288:A:AG	acceptor_gain	1.0000
X:107639288:ATT:A	acceptor_gain	1.0000
X:107639289:T:G	acceptor_gain	1.0000
X:107639290:T:A	acceptor_gain	1.0000
X:107639290:TGTA:T	acceptor_loss	1.0000
X:107639291:GTA:G	acceptor_loss	1.0000
X:107639292:TA:T	acceptor_loss	1.0000
X:107639293:A:AG	acceptor_gain	1.0000
X:107639293:AGT:A	acceptor_gain	1.0000
X:107639293:AGTGT:A	acceptor_gain	1.0000
X:107639294:G:GT	acceptor_gain	1.0000
X:107639294:GT:G	acceptor_gain	1.0000
X:107639294:GTG:G	acceptor_gain	1.0000
X:107639294:GTGTG:G	acceptor_gain	1.0000
X:107639474:A:G	donor_gain	1.0000
X:107639475:TAAGG:T	donor_loss	1.0000
X:107639477:AGG:A	donor_loss	1.0000
X:107639478:GGTAG:G	donor_loss	1.0000
X:107639479:G:C	donor_loss	1.0000
X:107639480:T:A	donor_loss	1.0000
X:107642488:GAG:G	donor_gain	1.0000
X:107645174:CAG:C	acceptor_gain	1.0000
X:107645175:A:AG	acceptor_gain	1.0000
X:107645175:AGA:A	acceptor_gain	1.0000
X:107645175:AGAGT:A	acceptor_gain	1.0000

AlphaMissense

2115 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:107628731:T:C	F35L	1.000
X:107628733:C:A	F35L	1.000
X:107628733:C:G	F35L	1.000
X:107639401:T:C	C77R	1.000
X:107639435:T:A	V88D	1.000
X:107639464:G:C	D98H	1.000
X:107639465:A:T	D98V	1.000
X:107639469:G:C	K99N	1.000
X:107639469:G:T	K99N	1.000
X:107639472:A:C	K100N	1.000
X:107639472:A:T	K100N	1.000
X:107640921:C:A	A109D	1.000
X:107640927:T:C	L111P	1.000
X:107640978:A:T	D128V	1.000
X:107640981:T:C	L129P	1.000
X:107640983:C:A	H130N	1.000
X:107640983:C:G	H130D	1.000
X:107640984:A:G	H130R	1.000
X:107640985:T:A	H130Q	1.000
X:107640985:T:G	H130Q	1.000
X:107640994:A:C	Q133H	1.000
X:107640994:A:T	Q133H	1.000
X:107642366:G:C	G136R	1.000
X:107642366:G:T	G136C	1.000
X:107642367:G:A	G136D	1.000
X:107642369:T:C	F137L	1.000
X:107642371:T:A	F137L	1.000
X:107642371:T:G	F137L	1.000
X:107642372:T:C	F138L	1.000
X:107642374:T:A	F138L	1.000

dbSNP variants (sampled 300 via entrez): RS1000128937 (X:107634894 C>T), RS1000145530 (X:107629249 T>C), RS1000255630 (X:107650641 T>C), RS1000654209 (X:107636919 GA>G), RS1000729898 (X:107636593 G>A,T), RS1000736840 (X:107649236 C>T), RS1000950589 (X:107636171 G>A,T), RS1001113263 (X:107646604 A>G), RS1001185015 (X:107635250 C>T), RS1001352976 (X:107643968 A>G), RS1001405395 (X:107634985 G>A), RS1001867348 (X:107645871 G>C,T), RS1001928564 (X:107633939 T>TA), RS1002080606 (X:107627557 C>T), RS1002315495 (X:107634593 A>G)

Disease associations

OMIM: gene MIM:311850 | disease phenotypes: MIM:311070, MIM:301835, MIM:300661, MIM:304500

GenCC curated gene-disease

Disease	Classification	Inheritance
phosphoribosylpyrophosphate synthetase superactivity	Definitive	X-linked
PRPS1 deficiency disorder	Definitive	X-linked
Arts syndrome	Definitive	X-linked
Charcot-Marie-Tooth disease X-linked recessive 5	Definitive	X-linked
hearing loss, X-linked 1	Definitive	X-linked
mild phosphoribosylpyrophosphate synthetase superactivity	Supportive	X-linked
severe phosphoribosylpyrophosphate synthetase superactivity	Supportive	X-linked
X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome	Supportive	X-linked
X-linked nonsyndromic hearing loss	Supportive	X-linked

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
phosphoribosylpyrophosphate synthetase superactivity	Limited	XL
PRPS1 deficiency disorder	Definitive	XL

Mondo (10): Charcot-Marie-Tooth disease X-linked recessive 5 (MONDO:0010699), Arts syndrome (MONDO:0010533), phosphoribosylpyrophosphate synthetase superactivity (MONDO:0010395), hearing loss, X-linked 1 (MONDO:0010577), PRPS1 deficiency disorder (MONDO:0100061), inherited retinal dystrophy (MONDO:0019118), mild phosphoribosylpyrophosphate synthetase superactivity (MONDO:0018463), severe phosphoribosylpyrophosphate synthetase superactivity (MONDO:0018464), X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome (MONDO:0018495), X-linked nonsyndromic hearing loss (MONDO:0019586)

Orphanet (5): X-linked Charcot-Marie-Tooth disease type 5 (Orphanet:99014), Lethal ataxia with deafness and optic atrophy (Orphanet:1187), Phosphoribosylpyrophosphate synthetase superactivity (Orphanet:3222), Rare X-linked non-syndromic sensorineural deafness type DFN (Orphanet:90625), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

144 total (30 of 144 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000083	Renal insufficiency
HP:0000154	Wide mouth
HP:0000218	High palate
HP:0000268	Dolichocephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000430	Underdeveloped nasal alae
HP:0000444	Convex nasal ridge
HP:0000467	Neck muscle weakness
HP:0000478	Abnormality of the eye
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000529	Progressive visual loss
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000556	Retinal dystrophy
HP:0000572	Visual loss
HP:0000577	Exotropia

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
C535388	Arts syndrome (supp.)
C564433	Deafness, X-Linked 1 (supp.)
C567064	Phosphoribosylpyrophosphate Synthetase Superactivity (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2638 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 27 predictive associations from 27 curated evidence items; also 10 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
PRPS1 A190T	Mercaptopurine + Lometrexol	B-lymphoblastic Leukemia/lymphoma	Sensitivity/Response	CIViC D	EID7913
PRPS1 L191F	Cytarabine	B-lymphoblastic Leukemia/lymphoma	Sensitivity/Response	CIViC D	EID7911
PRPS1 N144S	Cytarabine	B-lymphoblastic Leukemia/lymphoma	Sensitivity/Response	CIViC D	EID7910
PRPS1 S103T	Mercaptopurine + Lometrexol	B-lymphoblastic Leukemia/lymphoma	Sensitivity/Response	CIViC D	EID7912
PRPS1 A190T	Mercaptopurine + Thioguanine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7909
PRPS1 A190T	Cytarabine + Asparaginase + Methotrexate + Daunorubicin	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7928
PRPS1 A87T	Thioguanine + Mercaptopurine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7919
PRPS1 C77S	Thioguanine + Mercaptopurine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7916
PRPS1 D139G	Thioguanine + Mercaptopurine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7915
PRPS1 D183E	Thioguanine + Mercaptopurine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7900
PRPS1 D183E	Asparaginase + Methotrexate + Cytarabine + Daunorubicin	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7927
PRPS1 I72V	Mercaptopurine + Thioguanine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7917
PRPS1 K176N	Mercaptopurine + Thioguanine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7901
PRPS1 K176N	Daunorubicin + Cytarabine + Methotrexate + Asparaginase	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7926
PRPS1 L191F	Mercaptopurine + Thioguanine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7899
PRPS1 L191F	Asparaginase + Daunorubicin + Methotrexate	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7923
PRPS1 M115T	Thioguanine + Mercaptopurine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7920
PRPS1 N144S	Mercaptopurine + Thioguanine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7903
PRPS1 N144S	Daunorubicin + Methotrexate + Asparaginase	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7930
PRPS1 S103I	Mercaptopurine + Thioguanine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7905
PRPS1 S103N	Thioguanine + Mercaptopurine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7906
PRPS1 S103N	Methotrexate + Asparaginase + Daunorubicin + Cytarabine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7925
PRPS1 S103T	Thioguanine + Mercaptopurine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7907
PRPS1 S103T	Methotrexate + Asparaginase + Daunorubicin + Cytarabine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7924
PRPS1 T303S	Mercaptopurine + Thioguanine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7898
PRPS1 T303S	Asparaginase + Daunorubicin + Cytarabine + Methotrexate	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7929
PRPS1 V53A	Thioguanine + Mercaptopurine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID7918

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

ChEMBL bioactivities

89 potent at pChembl≥5 of 89 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.52	IC50	300	nM	CHEMBL6006962
6.52	IC50	300	nM	CHEMBL5957054
6.52	IC50	300	nM	CHEMBL5747382
6.52	IC50	300	nM	CHEMBL5953457
6.52	IC50	300	nM	CHEMBL5760889
6.52	IC50	300	nM	CHEMBL5819345
6.52	IC50	300	nM	CHEMBL5971455
6.52	IC50	300	nM	CHEMBL6008084
6.52	IC50	300	nM	CHEMBL6003991
6.52	IC50	300	nM	CHEMBL5836543
6.52	IC50	300	nM	CHEMBL5741050
6.52	IC50	300	nM	CHEMBL5969912
6.52	IC50	300	nM	CHEMBL6001851
6.52	IC50	300	nM	CHEMBL5835753
6.52	IC50	300	nM	CHEMBL6053341
6.52	IC50	300	nM	CHEMBL6038509
6.52	IC50	300	nM	CHEMBL5925218
6.52	IC50	300	nM	CHEMBL6000427
6.52	IC50	300	nM	CHEMBL5939097
6.52	IC50	300	nM	CHEMBL5851825
6.52	IC50	300	nM	CHEMBL5952358
6.52	IC50	300	nM	CHEMBL5972529
6.52	IC50	300	nM	CHEMBL5941824
6.52	IC50	300	nM	CHEMBL6003969
6.52	IC50	300	nM	CHEMBL5824001
6.52	IC50	300	nM	CHEMBL6017700
6.52	IC50	300	nM	CHEMBL5992961
6.52	IC50	300	nM	CHEMBL5884326
6.52	IC50	300	nM	CHEMBL5987920
6.52	IC50	300	nM	CHEMBL5816494
6.52	IC50	300	nM	CHEMBL6035471
6.52	IC50	300	nM	CHEMBL5824469
6.52	IC50	300	nM	CHEMBL5962209
6.52	IC50	300	nM	CHEMBL5884556
6.52	IC50	300	nM	CHEMBL5868005
6.52	IC50	300	nM	CHEMBL5805949
6.52	IC50	300	nM	CHEMBL5740837
6.52	IC50	300	nM	CHEMBL6043389
6.52	IC50	300	nM	CHEMBL5953804
6.52	IC50	300	nM	CHEMBL5810377
6.52	IC50	300	nM	CHEMBL5872647
6.52	IC50	300	nM	CHEMBL5997689
6.52	IC50	300	nM	CHEMBL5988827
6.52	IC50	300	nM	CHEMBL5950523
6.52	IC50	300	nM	CHEMBL5833044
6.52	IC50	300	nM	CHEMBL5811498
6.52	IC50	300	nM	CHEMBL6031140
6.52	IC50	300	nM	CHEMBL6008585
6.52	IC50	300	nM	CHEMBL5965899
6.52	IC50	300	nM	CHEMBL6014472

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression, affects expression	5
bisphenol A	decreases expression	4
Tretinoin	decreases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
bisphenol AF	decreases expression, increases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Arsenic	increases methylation, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Smoke	decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	increases expression	1
moringin	affects cotreatment, increases expression	1
chloroacetaldehyde	increases expression	1
afimoxifene	increases expression	1
butyraldehyde	increases expression	1
butylidenephthalide	decreases expression	1
tamibarotene	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4335422	Binding	Binding affinity to PRPS1 (unknown origin)	Discovery, Optimization, and Target Identification of Novel Potent Broad-Spectrum Antiviral Inhibitors. — J Med Chem

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_B3F1	Abcam HEK293T PRPS1 KO	Transformed cell line	Female
CVCL_TH23	HAP1 PRPS1 (-) 1	Cancer cell line	Male
CVCL_TH24	HAP1 PRPS1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT05912270	Not specified	RECRUITING	Orchestra in Class, a Novel Booster for Executive Functions and Brain Development in Young Primary School Children
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases
NCT07502664	Not specified	RECRUITING	Development and Evaluation of Functional Visual Field and Navigation Endpoints in Moderate to Profound Inherited Retinal Disease (DEFINE-IRD)
NCT07529041	Not specified	ENROLLING_BY_INVITATION	Real-time Acoustic Biofeedback for Enhancing Fixation Stability: A Proof-of-concept Study to Improve Ophthalmic Imaging Diagnostic Quality