HPRT1

Summary

HPRT1 (hypoxanthine phosphoribosyltransferase 1, HGNC:5157) is a protein-coding gene on chromosome Xq26.2-q26.3, encoding Hypoxanthine-guanine phosphoribosyltransferase (P00492). Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a transferase, which catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate via transfer of the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate. This enzyme plays a central role in the generation of purine nucleotides through the purine salvage pathway. Mutations in this gene result in Lesch-Nyhan syndrome or gout.

Source: NCBI Gene 3251 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Lesch-Nyhan syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 342 total — 83 pathogenic, 29 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000194

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5157
Approved symbol	HPRT1
Name	hypoxanthine phosphoribosyltransferase 1
Location	Xq26.2-q26.3
Locus type	gene with protein product
Status	Approved
Aliases	HGPRT
Ensembl gene	ENSG00000165704
Ensembl biotype	protein_coding
OMIM	308000
Entrez	3251

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000298556, ENST00000462974, ENST00000475720, ENST00000883913, ENST00000883914, ENST00000916519, ENST00000916520, ENST00000969779, ENST00000969780, ENST00000969781

RefSeq mRNA: 1 — MANE Select: NM_000194 NM_000194

CCDS: CCDS14641

Canonical transcript exons

ENST00000298556 — 9 exons

Exon	Start	End
ENSE00001904310	134500030	134500668
ENSE00001913528	134460165	134460338
ENSE00003489858	134473359	134473465
ENSE00003495603	134498608	134498684
ENSE00003522510	134490188	134490205
ENSE00003576599	134493508	134493590
ENSE00003623041	134475181	134475364
ENSE00003674574	134486465	134486530
ENSE00003676328	134498390	134498436

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.9005 / max 620.4743, expressed in 1820 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197604	17.8242	1793
197606	17.1954	1777
197603	16.5589	1805
197605	3.3220	1480

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.37	gold quality
secondary oocyte	CL:0000655	98.83	gold quality
middle temporal gyrus	UBERON:0002771	98.42	gold quality
pons	UBERON:0000988	98.13	gold quality
endothelial cell	CL:0000115	97.61	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.61	gold quality
orbitofrontal cortex	UBERON:0004167	97.23	gold quality
corpus epididymis	UBERON:0004359	97.18	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.11	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.81	gold quality
superior frontal gyrus	UBERON:0002661	96.75	gold quality
right testis	UBERON:0004534	96.69	gold quality
prefrontal cortex	UBERON:0000451	96.67	gold quality
substantia nigra pars compacta	UBERON:0001965	96.29	gold quality
adult organism	UBERON:0007023	96.28	gold quality
frontal cortex	UBERON:0001870	96.21	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.17	gold quality
left testis	UBERON:0004533	95.88	gold quality
cingulate cortex	UBERON:0003027	95.84	gold quality
superior vestibular nucleus	UBERON:0007227	95.84	gold quality
neocortex	UBERON:0001950	95.82	gold quality
anterior cingulate cortex	UBERON:0009835	95.77	gold quality
primary visual cortex	UBERON:0002436	95.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.75	gold quality
testis	UBERON:0000473	95.61	gold quality
cerebral cortex	UBERON:0000956	95.61	gold quality
hypothalamus	UBERON:0001898	95.58	gold quality
occipital lobe	UBERON:0002021	95.56	gold quality
postcentral gyrus	UBERON:0002581	95.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	32.15
E-GEOD-125970	yes	16.41
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting HPRT1, 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-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5003-3P	99.85	69.29	2517

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The purine salvage pathway of HGPRT, achieved by catalytically sequential steps leading to and from a favorable transition state, is the major route for purine nucleotide uptake in Plasmodium falciparum, the most virulent infective agent of malaria. (PMID:11434773)
• recurrent large Alu-mediated deletion associated with Lesch-Nyhan syndrome (PMID:11668636)
• High frequency of deletions at the hypoxanthine-guanine phosphoribosyltransferase locus in an ataxia-telangiectasia lymphoblastoid cell line irradiated with gamma-rays. (PMID:11714443)
• This report highlights the unusual occurrence of recurrent acute renal failure in a child with partial HPRT enzyme deficiency. (PMID:11891689)
• A comparative spectral analysis of somatic mutations at the HPRT reporter gene locus in healthy children revealed an age-specific decrease in large alterations and a corresponding increase in small alterations with increasing age. (PMID:12175903)
• HPRT and G6PD origins of replication that are functional in the active X chromosome are utilized even when the two genes are transcriptionally silent in the inactive X chromosome (PMID:12616531)
• In children with cancer there is no significant increase in background HPRT mutation frequency. (PMID:12874812)
• elevated HPRT mutation rates in a colon cancer cell line are caused by mutations in the MSH6 gene, and not in the POLD1 gene (PMID:14767555)
• how mutable and nonmutated amino acid residues in the HPRT monomer correlate with sequence conservation and predicted phenotypic effects (PMID:15146465)
• mutation of F36 residue in the core of the protein affects the stability of the enzyme (PMID:15178494)
• Mutation in the HPRT1 allele at the DNA and RNA levels in Lesch-Nyhan disease blastocyst. (PMID:15277709)
• summary of mutations in HPRT1 causing HPRT deficiency (PMID:15571220)
• a mutation of ATT to ACT (substitution of isoleucine to threonine) was found in codon 137 of HPRT in a patient with partial deficiency of the enzyme (PMID:15571222)
• analysis of exons of HPRT from the genomic DNA of Asian HPRT deficient families (PMID:15571223)
• a mutation with unknown sequence was identified in HPRT1 genomic DNA of a patient with Lesch-Nyhan syndrome (PMID:15571224)
• Splice variations of hypoxanthine phosphoribosyl transferase may be caused by aberrant splicing. (PMID:15601998)
• reports the identification, by competitive PCR of nascent DNA, of a replication origin in intron 2 of the human X-linked HPRT gene, that is functional only on the inactive X (PMID:15779006)
• Mother and both twins are heterozygous carriers of a HPRT splicing mutation, but an affected twin demonstrates a phenotype is classical for Lesch-Nyhan disease. (PMID:15862283)
• HPRT deficiency which appears to be due to a defect in the regulation of the gene in an individual with gout. (PMID:15862284)
• both active maternal smoking and secondary maternal exposure produce quantitatively and qualitatively indistinguishable increases in fetal HPRT mutation (PMID:15987524)
• snapshots of the structure of this enzyme in complex with substrates along the reaction pathway have been captured (PMID:15990111)
• A new mutation in the HPRT gene has been determined in one patient with complete deficiency of erythrocyte activity, with hyperuricemia and gout but without Lesch-Nyhan disease. (PMID:16216473)
• Partial HGPRT deficiency case presented as acute renal failure. (PMID:16240158)
• analysis of human HPRT1 pseudogenes (PMID:16355393)
• Mutations do not confer a growth advantage to somatic heterozygous clusters or maintenance turnover units. (PMID:16458330)
• Significant increase in the proportion of CpG transitions in this enzyme following treatment drug therapy in acute lymhpocytic leukemia in children. (PMID:16951156)
• a number of HPRT mutations in Asian patients manifesting different clinical phenotypes. (PMID:17027311)
• mutational analysis of HPRT in patients with Lesch-Nyhan Disease, HPRT-related hyperuricemia with neurologic dysfunction, and hyperuricemia (PMID:17454734)
• Expression of candidate genes HPRT1 and ALAS1 in malignant and non-malignant prostate tissue samples after microdissection. (PMID:17628775)
• tested the hypothesis that inheritance of the L84F and I143V coding single nucleotide polymorphism in the MGMT gene is associated with increases in HPRT mutant frequency in lymphocytes of smokers (PMID:17700363)
• We report on a rare case of hypoxanthine guanine phosphoribosyl transferase (HGPRT) deficiency that presented in the newborn period with acute renal failure (ARF). (PMID:17934765)
• Lesch-Nyhan syndrome was due to a defect in HPRT gene expression regulation. (PMID:18316217)
• Acrylamide has a weak mutagenic effect at HPRT gene locus in human promyelocytic leukaemia HL-60 and NB4 cell lines. (PMID:18407966)
• mutations within the gene give rise to Lesch-Nyhan syndrome (PMID:18409516)
• intrachromosomal genomic rearrangements on the Mbp scale represent the prevailing type of radiation-induced HPRT mutations (PMID:18494542)
• two novel mutations were identified in this study: a single nucleotide substitution (430C > T) resulting in a nonsense mutation Q144X, and a deletion of HPRT1 exon 1 expressing no mRNA of HPRT (PMID:18600506)
• Kinetic analysis of the active mutants (E196A, E196D, E196Q, and E196R) suggests that interaction between K68 and E196 side chains contributes to stabilization of cis-configuration during the catalytic cycle (PMID:18600559)
• a HPRT mutation (IVS6 + 2) led to deletion of exon 6 in 5 members of a family; affected members fell into 3 differing phenotypes; 1 displayed classic Lesch-Nyhan phenotype, 2 had a much milder disease, and 2 had an intermediate phenotype (PMID:18779430)
• Report lack of any common mutation causing HPRT deficiency in Poland. (PMID:19016344)
• HPRT deficiency influences the development of dopamine neurons and their neurochemical phenotype. (PMID:19342420)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hprt1	ENSDARG00000008884
mus_musculus	Hprt1	ENSMUSG00000025630
rattus_norvegicus	Hprt1	ENSRNOG00000031367
drosophila_melanogaster	Pgm1	FBGN0003076
caenorhabditis_elegans		WBGENE00019890

Paralogs (6): PGM3 (ENSG00000013375), PGM1 (ENSG00000079739), PRTFDC1 (ENSG00000099256), PGM5 (ENSG00000154330), PGM2L1 (ENSG00000165434), PGM2 (ENSG00000169299)

Protein

Protein identifiers

Hypoxanthine-guanine phosphoribosyltransferase — P00492 (reviewed: P00492)

All UniProt accessions (2): P00492, A0A140VJL3

UniProt curated annotations — full annotation on UniProt →

Function. Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.

Subunit / interactions. Homotetramer.

Subcellular location. Cytoplasm.

Disease relevance. Lesch-Nyhan syndrome (LNS) [MIM:300322] Characterized by complete lack of enzymatic activity that results in hyperuricemia, choreoathetosis, intellectual disability, and compulsive self-mutilation. The disease is caused by variants affecting the gene represented in this entry. Hyperuricemia, HPRT-related (HRH) [MIM:300323] An X-linked metabolic disorder characterized by uric acid excess in the blood, renal stones, uric acid nephropathy, and renal obstruction. After puberty, the hyperuricemia may cause gout. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 magnesium ions per subunit. The magnesium ions are essentially bound to the substrate and have few direct interactions with the protein.

Pathway. Purine metabolism; IMP biosynthesis via salvage pathway; IMP from hypoxanthine: step 1/1.

Similarity. Belongs to the purine/pyrimidine phosphoribosyltransferase family.

RefSeq proteins (1): NP_000185* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000836	PRTase_dom	Domain
IPR005904	Hxn_phspho_trans	Family
IPR029057	PRTase-like	Homologous_superfamily
IPR050408	HGPRT	Family

Pfam: PF00156

Enzyme classification (BRENDA):

• EC 2.4.2.8 — hypoxanthine phosphoribosyltransferase (BRENDA: 43 organisms, 230 substrates, 274 inhibitors, 271 Km, 191 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
5-PHOSPHO-ALPHA-D-RIBOSE 1-DIPHOSPHATE	0.001–3.668	85
HYPOXANTHINE	0.0005–0.126	59
GUANINE	0.0008–0.5	58
XANTHINE	0.02–0.853	15
DIPHOSPHATE	0.0039–0.968	13
IMP	0.0016–1.043	9
INOSINE MONOPHOSPHATE	0.0054–0.09	3
5-PHOSPHORIBOSYL 1-DIPHOSPHATE	0.127–0.138	2
6-MERCAPTOPURINE	0.0062–0.041	2
6-THIOGUANINE	0.0033–0.0076	2
ALLOPURINOL	0.0117–0.135	2
GMP	0.0225–0.029	2
3-HYDROXY-2-PYRAZINECARBOXAMIDE	4.069	1
6-FLUORO-3-HYDROXY-2-PYRAZINECARBOXAMIDE	6.426	1
6-THIOXANTHINE	0.032	1

Catalyzed reactions (Rhea), 2 shown:

• IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate (RHEA:17973)
• GMP + diphosphate = guanine + 5-phospho-alpha-D-ribose 1-diphosphate (RHEA:25424)

UniProt features (115 total): sequence variant 73, strand 16, helix 9, binding site 6, modified residue 3, cross-link 2, turn 2, initiator methionine 1, chain 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
5HIA	X-RAY DIFFRACTION	1.77
4RAO	X-RAY DIFFRACTION	1.87
1Z7G	X-RAY DIFFRACTION	1.9
6BNJ	X-RAY DIFFRACTION	1.91
1BZY	X-RAY DIFFRACTION	2
4RAD	X-RAY DIFFRACTION	2
4IJQ	X-RAY DIFFRACTION	2
4RAC	X-RAY DIFFRACTION	2.05
4RAB	X-RAY DIFFRACTION	2.26
8TPV	X-RAY DIFFRACTION	2.27
5BRN	X-RAY DIFFRACTION	2.3
5W8V	X-RAY DIFFRACTION	2.35
1HMP	X-RAY DIFFRACTION	2.5
8TPY	X-RAY DIFFRACTION	2.5
4RAQ	X-RAY DIFFRACTION	2.53
4RAN	X-RAY DIFFRACTION	2.55
7SAN	X-RAY DIFFRACTION	2.58
3GEP	X-RAY DIFFRACTION	2.6
3GGJ	X-RAY DIFFRACTION	2.6
5BSK	X-RAY DIFFRACTION	2.61
1D6N	X-RAY DIFFRACTION	2.7
4KN6	X-RAY DIFFRACTION	2.73
3GGC	X-RAY DIFFRACTION	2.78
2VFA	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00492-F1	92.84	0.86

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): 138 (proton acceptor)

Ligand- & substrate-binding residues (6): 69; 134–142; 166; 186–188; 194; 194

Post-translational modifications (5): 103, 142, 115, 115, 2

Mutagenesis-validated functional residues (1):

Position	Phenotype
69	reduced affinity for hypoxanthine, phosphoribosylpyrophosphate and imp. reduced catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-74217	Purine salvage
R-HSA-9734281	Defective HPRT1 disrupts guanine and hypoxanthine salvage
R-HSA-9748787	Azathioprine ADME

MSigDB gene sets: 423 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_DENDRITE_DEVELOPMENT, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_AMINE, GOBP_PROTEIN_HOMOTETRAMERIZATION, BASSO_B_LYMPHOCYTE_NETWORK, MODULE_56, MODULE_151, GOBP_POSITIVE_REGULATION_OF_AMINE_METABOLIC_PROCESS, MORF_UBE2I, MORF_RAD21

GO Biological Process (24): T cell mediated cytotoxicity (GO:0001913), response to amphetamine (GO:0001975), purine nucleotide biosynthetic process (GO:0006164), purine ribonucleoside salvage (GO:0006166), guanine salvage (GO:0006178), grooming behavior (GO:0007625), locomotory behavior (GO:0007626), striatum development (GO:0021756), cerebral cortex neuron differentiation (GO:0021895), central nervous system neuron development (GO:0021954), GMP salvage (GO:0032263), IMP salvage (GO:0032264), dopamine metabolic process (GO:0042417), hypoxanthine salvage (GO:0043103), AMP salvage (GO:0044209), positive regulation of dopamine metabolic process (GO:0045964), GMP catabolic process (GO:0046038), IMP metabolic process (GO:0046040), adenine metabolic process (GO:0046083), hypoxanthine metabolic process (GO:0046100), lymphocyte proliferation (GO:0046651), dendrite morphogenesis (GO:0048813), protein homotetramerization (GO:0051289), dopaminergic neuron differentiation (GO:0071542)

GO Molecular Function (9): nucleotide binding (GO:0000166), magnesium ion binding (GO:0000287), hypoxanthine phosphoribosyltransferase activity (GO:0004422), identical protein binding (GO:0042802), guanine phosphoribosyltransferase activity (GO:0052657), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), metal ion binding (GO:0046872)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062), sperm midpiece (GO:0097225), sperm annulus (GO:0097227), sperm principal piece (GO:0097228), sperm end piece (GO:0097229)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Nucleotide salvage	1
Nucleotide salvage defects	1
Drug ADME	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
sperm flagellum	4
purine ribonucleotide salvage	3
purine nucleobase salvage	2
behavior	2
purine nucleobase metabolic process	2
purine phosphoribosyltransferase activity	2
leukocyte mediated cytotoxicity	1
T cell mediated immunity	1
response to amine	1
purine nucleotide metabolic process	1
nucleotide biosynthetic process	1
purine-containing compound biosynthetic process	1
purine-containing compound salvage	1
nucleoside salvage	1
purine ribonucleoside biosynthetic process	1
guanine biosynthetic process	1
subpallium development	1
anatomical structure development	1
forebrain neuron differentiation	1
central nervous system neuron differentiation	1
neuron development	1
GMP biosynthetic process	1
IMP biosynthetic process	1
catecholamine metabolic process	1
hypoxanthine biosynthetic process	1
AMP biosynthetic process	1
positive regulation of amine metabolic process	1
regulation of dopamine metabolic process	1
dopamine metabolic process	1
purine ribonucleotide catabolic process	1
purine ribonucleoside monophosphate catabolic process	1
GMP metabolic process	1
purine ribonucleotide metabolic process	1
purine ribonucleoside monophosphate metabolic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
metal ion binding	1
protein binding	1
binding	1

Protein interactions and networks

STRING

5530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HPRT1	APRT	P07741	933
HPRT1	GAPDH	P00354	851
HPRT1	ACTB	P02570	794
HPRT1	HMBS	P08396	790
HPRT1	PGK1	P00558	766
HPRT1	ADK	P55263	766
HPRT1	TBP	P20226	762
HPRT1	B2M	P01884	737
HPRT1	GUSB	P08236	735
HPRT1	SDHA	P31040	722
HPRT1	PLAC1	Q9HBJ0	718
HPRT1	POTEF	A5A3E0	710
HPRT1	PNP	P00491	704
HPRT1	RPL13A	P40429	693
HPRT1	G6PD	P11413	674

IntAct

157 interactions, top by confidence:

A	B	Type	Score
HPRT1	PRTFDC1	psi-mi:“MI:0915”(physical association)	0.920
PRTFDC1	HPRT1	psi-mi:“MI:0915”(physical association)	0.920
NTAQ1	HPRT1	psi-mi:“MI:0915”(physical association)	0.880
HPRT1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.880
HPRT1	HPRT1	psi-mi:“MI:0915”(physical association)	0.800
SDCBP	HPRT1	psi-mi:“MI:0915”(physical association)	0.780
HPRT1	SDCBP	psi-mi:“MI:0915”(physical association)	0.780
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710

BioGRID (161): HPRT1 (Affinity Capture-MS), HPRT1 (Two-hybrid), SDCBP (Two-hybrid), ISCU (Two-hybrid), WDYHV1 (Two-hybrid), PRTFDC1 (Two-hybrid), HPRT1 (Affinity Capture-MS), WDYHV1 (Two-hybrid), PRTFDC1 (Two-hybrid), PPAT (Co-fractionation), HPRT1 (Proximity Label-MS), HPRT1 (Affinity Capture-MS), PRTFDC1 (Two-hybrid), PRTFDC1 (Affinity Capture-MS), HPRT1 (Affinity Capture-MS)

ESM2 similar proteins: A4II60, A5A6I1, B4S3A5, G5EDZ2, O42895, O65583, O74427, O94710, P00492, P00493, P00494, P07833, P09383, P20035, P27515, P27605, P41888, P43152, P47959, P56523, Q07010, Q10439, Q1RMS2, Q25566, Q26997, Q26998, Q27541, Q2M197, Q3SZ18, Q45FY6, Q55EL3, Q5F3Z1, Q64531, Q6DCP3, Q6GQ37, Q6LDD9, Q6LZE9, Q6WIT9, Q8VYB2, Q9FKS0

Diamond homologs: A4II60, A5A6I1, C0ZG45, O66821, O69537, P00492, P00493, P00494, P07833, P09383, P0A5T1, P0A9M2, P0A9M3, P0A9M4, P18134, P20035, P27605, P37171, P37472, P43152, P45078, P47959, P51900, P71479, P96794, P9WHQ8, P9WHQ9, Q02522, Q26997, Q3SZ18, Q45FY6, Q5HRP4, Q64531, Q6DCP3, Q6LDD9, Q6WIT9, Q724J4, Q839B2, Q8CQV4, Q8DRP8

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
HPRT1	“down-regulates quantity”	“5-phospho-α-D-ribose 1-diphosphate”	“chemical modification”
HPRT1	“down-regulates quantity”	guanine	“chemical modification”
HPRT1	“up-regulates quantity”	“guanosine 5’-monophosphate(2-)”	“chemical modification”
HPRT1	“down-regulates quantity”	hypoxanthine	“chemical modification”
HPRT1	“up-regulates quantity”	IMP	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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.

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	6	27.2×	8e-05
autophagosome assembly	6	17.1×	5e-04
negative regulation of gene expression	9	7.9×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	83
Likely pathogenic	29
Uncertain significance	63
Likely benign	74
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
10032	HPRT CHICAGO	Pathogenic
10033	HPRT CONNERSVILLE	Pathogenic
10037	NM_000194.2(HPRT1):c.580G>A (p.Asp194Asn)	Pathogenic
10039	HPRT MICHIGAN	Pathogenic
10040	NM_000194.2(HPRT1):c.389T>A (p.Val130Asp)	Pathogenic
10044	NM_000194.2(HPRT1):c.209G>A (p.Gly70Glu)	Pathogenic
10046	NM_000194.3(HPRT1):c.325C>T (p.Gln109Ter)	Pathogenic
10048	NM_000194.3(HPRT1):c.134G>A (p.Arg45Lys)	Pathogenic
10049	NM_000194.3(HPRT1):c.529G>T (p.Asp177Tyr)	Pathogenic
10050	NM_000194.3(HPRT1):c.317_318del	Pathogenic
10051	NM_000194.3(HPRT1):c.126del (p.Met43fs)	Pathogenic
10052	NM_000194.3(HPRT1):c.392del (p.Val130_Leu131insTer)	Pathogenic
10053	NM_000194.3(HPRT1):c.160_199del (p.Met54fs)	Pathogenic
10055	NM_000194.3(HPRT1):c.610-4_610-2delinsTTT	Pathogenic
10056	NM_000194.3(HPRT1):c.532+5G>A	Pathogenic
10057	NM_000194.3(HPRT1):c.28-2A>T	Pathogenic
10058	NM_000194.3(HPRT1):c.527C>T (p.Pro176Leu)	Pathogenic
10060	NM_000194.2(HPRT1):c.151C>T (p.Arg51Ter)	Pathogenic
10062	NM_000194.3(HPRT1):c.428T>A (p.Met143Lys)	Pathogenic
10065	NG_012329.2:g.(5195_18214)_(18322_20036)del	Pathogenic
10066	HPRT, EX4-9DEL	Pathogenic
10067	NC_000023.11:g.(134493178_134493182)_(134501172_134501176)del	Pathogenic
10068	HPRT, EX9DEL	Pathogenic
10071	HPRT, INV/DEL, EX6-9	Pathogenic
10072	HPRT, EX2-3DUP, IVS1DEL	Pathogenic
10073	NM_000194.2(HPRT1):c.503C>T (p.Thr168Ile)	Pathogenic
10077	HPRT CHERMSIDE	Pathogenic
10078	HPRT COORPAROO	Pathogenic
10084	NM_000194.3(HPRT1):c.193C>T (p.Leu65Phe)	Pathogenic
1039442	NM_000194.3(HPRT1):c.486-3C>G	Pathogenic

SpliceAI

1338 predictions. Top by Δscore:

Variant	Effect	Δscore
X:134473355:TCAG:T	acceptor_loss	1.0000
X:134473356:CA:C	acceptor_loss	1.0000
X:134473357:A:AG	acceptor_gain	1.0000
X:134473357:A:G	acceptor_loss	1.0000
X:134473358:G:GG	acceptor_gain	1.0000
X:134473358:GA:G	acceptor_gain	1.0000
X:134473358:GATT:G	acceptor_gain	1.0000
X:134473358:GATTA:G	acceptor_gain	1.0000
X:134473461:GACAG:G	donor_gain	1.0000
X:134473463:CAG:C	donor_gain	1.0000
X:134473464:AGGT:A	donor_loss	1.0000
X:134473465:GGTA:G	donor_loss	1.0000
X:134473466:G:GG	donor_gain	1.0000
X:134473467:T:G	donor_loss	1.0000
X:134475175:CTGTA:C	acceptor_loss	1.0000
X:134475176:TGTAG:T	acceptor_loss	1.0000
X:134475177:GTAG:G	acceptor_loss	1.0000
X:134475178:TAGG:T	acceptor_loss	1.0000
X:134475179:A:AG	acceptor_gain	1.0000
X:134475179:A:AT	acceptor_loss	1.0000
X:134475179:AG:A	acceptor_gain	1.0000
X:134475180:G:GA	acceptor_gain	1.0000
X:134475180:GG:G	acceptor_gain	1.0000
X:134475180:GGA:G	acceptor_gain	1.0000
X:134475180:GGAC:G	acceptor_gain	1.0000
X:134475180:GGACT:G	acceptor_gain	1.0000
X:134475361:TTGT:T	donor_gain	1.0000
X:134475361:TTGTG:T	donor_loss	1.0000
X:134475363:GT:G	donor_gain	1.0000
X:134475363:GTGTG:G	donor_loss	1.0000

AlphaMissense

1448 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:134475341:T:C	F99L	1.000
X:134475343:T:A	F99L	1.000
X:134475343:T:G	F99L	1.000
X:134498634:T:C	F187L	1.000
X:134498636:T:A	F187L	1.000
X:134498636:T:G	F187L	1.000
X:134498644:G:A	G190E	1.000
X:134498674:G:C	R200T	1.000
X:134498674:G:T	R200M	1.000
X:134475242:T:C	C66R	0.999
X:134475243:G:A	C66Y	0.999
X:134475244:T:G	C66W	0.999
X:134475249:T:A	L68H	0.999
X:134475249:T:C	L68P	0.999
X:134475254:G:A	G70R	0.999
X:134475254:G:C	G70R	0.999
X:134475255:G:A	G70E	0.999
X:134475258:G:A	G71D	0.999
X:134475279:T:C	L78P	0.999
X:134490192:T:A	V130D	0.999
X:134490195:T:C	L131S	0.999
X:134490198:T:A	I132N	0.999
X:134490204:A:T	E134V	0.999
X:134493508:G:C	D135H	0.999
X:134493509:A:T	D135V	0.999
X:134493521:C:T	T139I	0.999
X:134493589:A:C	S162R	0.999
X:134498390:C:A	S162R	0.999
X:134498390:C:G	S162R	0.999
X:134498401:A:T	K166I	0.999

dbSNP variants (sampled 300 via entrez): RS1000138791 (X:134487723 T>C), RS1000171875 (X:134484640 G>T), RS1000180453 (X:134464650 T>C), RS1000189373 (X:134498698 T>G), RS1000513891 (X:134493632 A>C,G), RS1000528223 (X:134474457 C>T), RS1000539518 (X:134497038 T>TATAACA), RS1000605844 (X:134487057 T>A), RS1000671664 (X:134462831 T>A), RS1000869624 (X:134463252 A>G), RS1001477718 (X:134471786 G>A), RS1001507784 (X:134496904 T>A,C), RS1001604233 (X:134496411 T>G), RS1001668941 (X:134470178 A>G), RS1001691197 (X:134492924 A>C)

Disease associations

OMIM: gene MIM:308000 | disease phenotypes: MIM:300323, MIM:300322

GenCC curated gene-disease

Disease	Classification	Inheritance
Lesch-Nyhan syndrome	Definitive	X-linked
hypoxanthine guanine phosphoribosyltransferase partial deficiency	Strong	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Lesch-Nyhan syndrome	Definitive	XL

Mondo (3): hypoxanthine guanine phosphoribosyltransferase partial deficiency (MONDO:0010299), Lesch-Nyhan syndrome (MONDO:0010298), microcephaly (MONDO:0001149)

Orphanet (2): Hypoxanthine guanine phosphoribosyltransferase partial deficiency (Orphanet:79233), Lesch-Nyhan syndrome (Orphanet:510)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000029	Testicular atrophy
HP:0000083	Renal insufficiency
HP:0000112	Nephropathy
HP:0000121	Nephrocalcinosis
HP:0000707	Abnormality of the nervous system
HP:0000708	Atypical behavior
HP:0000742	Self-mutilation
HP:0000787	Nephrolithiasis
HP:0000790	Hematuria
HP:0000791	Uric acid nephrolithiasis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001270	Motor delay
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0001419	X-linked recessive inheritance
HP:0001854	Podagra
HP:0001889	Megaloblastic anemia
HP:0001903	Anemia
HP:0001919	Acute kidney injury
HP:0001997	Gout
HP:0002013	Vomiting
HP:0002015	Dysphagia
HP:0002071	Abnormality of extrapyramidal motor function

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007876_62	Estimated glomerular filtration rate	5.000000e-08

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D007926	Lesch-Nyhan Syndrome	C10.228.140.163.100.425; C10.597.606.360.455.625; C16.320.322.500.625; C16.320.400.525.625; C16.320.565.189.425; C16.320.565.798.594; C18.452.132.100.425; C18.452.648.189.425; C18.452.648.798.594
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C562583	Gout, HPRT-Related (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2360 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

4 measured of 4 human assays (27 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
HGXPRT Inhibitor, 3	KI	385 nM
US9200020, Table 1, Compound 1	KI	1000 nM	US-9200020: 6-oxopurine phosphoribosyltransferase inhibitors
US9200020, Table 1, Compound 1B	KI	3600 nM	US-9200020: 6-oxopurine phosphoribosyltransferase inhibitors
HGXPRT Inhibitor, 2	KI	4940 nM

ChEMBL bioactivities

171 potent at pChembl≥5 of 214 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Ki	1	nM	CHEMBL4282830
8.89	Ki	1.3	nM	CHEMBL4282830
8.89	Ki	1.3	nM	CHEMBL5184028
8.74	Ki	1.8	nM	CHEMBL1233663
8.52	Ki	3	nM	CHEMBL4290716
8.52	Ki	3	nM	CHEMBL5573402
8.34	Ki	4.6	nM	CHEMBL1233603
8.22	Ki	6	nM	CHEMBL4086362
8.22	Ki	6	nM	CHEMBL5207635
8.10	Ki	8	nM	CHEMBL4285691
8.10	Ki	8	nM	CHEMBL4277753
8.05	Ki	9	nM	CHEMBL5591537
8.00	Ki	10	nM	CHEMBL3578115
7.70	Ki	20	nM	CHEMBL5178774
7.52	Ki	30	nM	CHEMBL2325752
7.52	Ki	30	nM	CHEMBL3394315
7.52	Ki	30	nM	CHEMBL3578110
7.52	Ki	30	nM	CHEMBL3578114
7.52	Ki	30	nM	CHEMBL4280490
7.52	Ki	30	nM	CHEMBL5198761
7.52	Ki	30	nM	CHEMBL5565343
7.40	Ki	40	nM	CHEMBL3394327
7.40	Ki	40	nM	CHEMBL3578112
7.25	Ki	56	nM	CHEMBL1233603
7.16	Ki	70	nM	CHEMBL2153480
7.16	Ki	70	nM	CHEMBL2153497
7.16	Ki	70	nM	CHEMBL4115916
7.16	Ki	70	nM	CHEMBL4115921
7.16	Ki	70	nM	CHEMBL5185227
7.10	Ki	80	nM	CHEMBL3394316
7.05	Ki	90	nM	CHEMBL5563998
7.00	Ki	100	nM	CHEMBL2153476
7.00	Ki	100	nM	CHEMBL2153478
7.00	Ki	100	nM	CHEMBL2153484
7.00	Ki	100	nM	CHEMBL2420072
7.00	Ki	100	nM	CHEMBL4115913
7.00	Ki	100	nM	CHEMBL4115915
7.00	Ki	100	nM	CHEMBL4115920
7.00	Ki	100	nM	CHEMBL4067618
7.00	Ki	100	nM	CHEMBL4078513
7.00	Ki	100	nM	CHEMBL4098313
7.00	Ki	100	nM	CHEMBL4546337
7.00	Ki	100	nM	CHEMBL5208021
7.00	Ki	100	nM	CHEMBL5171024
7.00	Ki	100	nM	CHEMBL594335
6.85	Ki	140	nM	CHEMBL5569467
6.82	Ki	150	nM	CHEMBL2153483
6.82	Ki	150	nM	CHEMBL4115919
6.82	Ki	150	nM	CHEMBL4846343
6.72	Ki	190	nM	CHEMBL3394312

PubChem BioAssay actives

155 with measured affinity, of 360 total; 50 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
[(1S)-1-hydroxy-2-[(3R,4R)-4-(6-oxo-1H-purin-9-yl)-1-(3-phosphonopropanoyl)pyrrolidin-3-yl]oxyethyl]phosphonic acid	1422149: Inhibition of human HGPRT using fixed concentration of guanine and variable concentrations of PRib-PP as substrate by spectrophotometric analysis	ki	0.0010	uM
tetrasodium;9-[(3R)-4-[(2S)-2-hydroxy-2-phosphonatoethoxy]-1-(3-phosphonatopropanoyl)pyrrolidin-3-yl]-1H-purin-6-one	1902599: Inhibition of human HGPRT using PRib-PP as substrate by spectrophotometric assay	ki	0.0013	uM
[(2R,3R,4S,5S)-3,4-dihydroxy-5-(4-oxo-3,5-dihydropyrrolo[3,2-d]pyrimidin-7-yl)pyrrolidin-2-yl]methyl dihydrogen phosphate	1578795: Inhibition of human HGPRT assessed as inhibitor constant for enzyme-inhibitor-substrate complex formation using [5’-14C]IMP as substrate by scintillation counting method	ki	0.0018	uM
[3-[(3R,4R)-3-(2-amino-6-oxo-1H-purin-9-yl)-4-[(2S)-2-hydroxy-2-phosphonoethoxy]pyrrolidin-1-yl]-3-oxopropyl]phosphonic acid	1422155: Inhibition of recombinant human HGPRT using fixed concentration of guanine and variable concentrations of PRib-PP as substrate by Hanes plot analysis	ki	0.0030	uM
[3-[(2S,4R)-4-(2-amino-6-oxo-1H-purin-9-yl)-2-(2-phosphonoethoxymethyl)pyrrolidin-1-yl]-3-oxopropyl]phosphonic acid	2105914: Inhibition of human HGPRT by spectrophotometry	ki	0.0030	uM
[(2R,3R,4S,5S)-5-(2-amino-4-oxo-3,5-dihydropyrrolo[3,2-d]pyrimidin-7-yl)-3,4-dihydroxypyrrolidin-2-yl]methyl dihydrogen phosphate	1578795: Inhibition of human HGPRT assessed as inhibitor constant for enzyme-inhibitor-substrate complex formation using [5’-14C]IMP as substrate by scintillation counting method	ki	0.0046	uM
tetrasodium;2-amino-9-[2-(2-phosphonatoethoxymethyl)-3-(phosphonatomethoxy)propyl]-1H-purin-6-one	1458942: Inhibition of human HGPRT using PRib-PP as the substrate by spectrophotometric method	ki	0.0060	uM
tetrasodium;2-[(2S)-2-[(2-amino-6-oxo-1H-purin-9-yl)methyl]-3-(phosphonatomethoxy)propoxy]ethyl phosphate	1902599: Inhibition of human HGPRT using PRib-PP as substrate by spectrophotometric assay	ki	0.0060	uM
[3-[(3R,4R)-3-(2-amino-6-oxo-1H-purin-9-yl)-4-[(2R)-2-hydroxy-2-phosphonoethoxy]pyrrolidin-1-yl]-3-oxopropyl]phosphonic acid	1422155: Inhibition of recombinant human HGPRT using fixed concentration of guanine and variable concentrations of PRib-PP as substrate by Hanes plot analysis	ki	0.0080	uM
[(1R)-1-hydroxy-2-[(3R,4R)-4-(6-oxo-1H-purin-9-yl)-1-(3-phosphonopropanoyl)pyrrolidin-3-yl]oxyethyl]phosphonic acid	1422149: Inhibition of human HGPRT using fixed concentration of guanine and variable concentrations of PRib-PP as substrate by spectrophotometric analysis	ki	0.0080	uM
[3-[(2S,4S)-4-(2-amino-6-oxo-1H-purin-9-yl)-2-(2-phosphonoethoxymethyl)pyrrolidin-1-yl]-3-oxopropyl]phosphonic acid	2105914: Inhibition of human HGPRT by spectrophotometry	ki	0.0090	uM
2-[2-[bis(2-phosphonoethyl)amino]ethyl-[2-(6-oxo-1H-purin-9-yl)ethyl]amino]ethylphosphonic acid	1226509: Inhibition of human HGPRT	ki	0.0100	uM
tetrasodium;9-[(3R)-4-(2-phosphonatoethoxy)-1-(3-phosphonatopropanoyl)pyrrolidin-3-yl]-1H-purin-6-one	1902599: Inhibition of human HGPRT using PRib-PP as substrate by spectrophotometric assay	ki	0.0200	uM
[2-[(2-amino-6-oxo-1H-purin-9-yl)methyl]-3-(phosphonomethoxy)propoxy]methylphosphonic acid	728128: Inhibition of human N-terminal hexahistidine-tagged HGPRT	ki	0.0300	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-(2-phosphonoethoxymethyl)amino]ethylphosphonic acid	1189879: Inhibition of human HGPRT	ki	0.0300	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-[2-[2-hydroxyethyl(2-phosphonoethyl)amino]ethyl]amino]ethylphosphonic acid	1226509: Inhibition of human HGPRT	ki	0.0300	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-[2-[bis(2-phosphonoethyl)amino]ethyl]amino]ethylphosphonic acid	1226509: Inhibition of human HGPRT	ki	0.0300	uM
[3-[(3R,4S)-3-(2-amino-6-oxo-1H-purin-9-yl)-4-(2-phosphonoethoxy)pyrrolidin-1-yl]-3-oxopropyl]phosphonic acid	1422149: Inhibition of human HGPRT using fixed concentration of guanine and variable concentrations of PRib-PP as substrate by spectrophotometric analysis	ki	0.0300	uM
tetrasodium;2-amino-9-[3-(phosphonatomethoxy)-2-(phosphonatomethoxymethyl)propyl]-1H-purin-6-one	1902599: Inhibition of human HGPRT using PRib-PP as substrate by spectrophotometric assay	ki	0.0300	uM
[3-[(2R,4R)-4-(2-amino-6-oxo-1H-purin-9-yl)-2-(2-phosphonoethoxymethyl)pyrrolidin-1-yl]-3-oxopropyl]phosphonic acid	2105914: Inhibition of human HGPRT by spectrophotometry	ki	0.0300	uM
2-[2-(2-amino-8-bromo-6-oxo-1H-purin-9-yl)ethyl-[2-(2-phosphonoethoxy)ethyl]amino]ethylphosphonic acid	1189879: Inhibition of human HGPRT	ki	0.0400	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-[2-[3-hydroxypropyl(2-phosphonoethyl)amino]ethyl]amino]ethylphosphonic acid	1226509: Inhibition of human HGPRT	ki	0.0400	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-(2-cyanoethyl)amino]ethylphosphonic acid	1189879: Inhibition of human HGPRT	ki	0.0700	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-(2-hydroxyethyl)amino]ethylphosphonic acid	689807: Inhibition of human HGPRT using Prib-PP as substrate by spectrophotometric assay in presence of guanine	ki	0.0700	uM
tetrasodium;2-amino-9-[(2S)-2-[(2S)-2-hydroxy-2-phosphonatoethoxy]-3-(phosphonatomethoxy)propyl]-1H-purin-6-one	1902599: Inhibition of human HGPRT using PRib-PP as substrate by spectrophotometric assay	ki	0.0700	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-[2-(2-phosphonoethoxy)ethyl]amino]ethylphosphonic acid	1189879: Inhibition of human HGPRT	ki	0.0800	uM
[3-[(2S,4R)-4-(2-amino-6-oxo-1H-purin-9-yl)-2-(hydroxymethyl)pyrrolidin-1-yl]-3-oxopropyl]phosphonic acid	2105914: Inhibition of human HGPRT by spectrophotometry	ki	0.0900	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethoxy]propylphosphonic acid	451291: Inhibition of human recombinant HGPRT expressed in Escherichia coli by spectrophotometric assay	ki	0.1000	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-(2-ethoxy-2-oxoethyl)amino]ethylphosphonic acid	689807: Inhibition of human HGPRT using Prib-PP as substrate by spectrophotometric assay in presence of guanine	ki	0.1000	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-(4-methoxy-4-oxobutyl)amino]ethylphosphonic acid	689807: Inhibition of human HGPRT using Prib-PP as substrate by spectrophotometric assay in presence of guanine	ki	0.1000	uM
4-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-(2-phosphonoethyl)amino]butanoic acid	689807: Inhibition of human HGPRT using Prib-PP as substrate by spectrophotometric assay in presence of guanine	ki	0.1000	uM
2-[(2S)-1-(2-amino-6-oxo-1H-purin-9-yl)-3-fluoropropan-2-yl]oxyethylphosphonic acid	768673: Inhibition of recombinant human HGPRT expressed in Escherichia coli Sphi606 cells by spectrophotometric analysis	ki	0.1000	uM
[1-[(2R)-1-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxypropan-2-yl]triazol-4-yl]phosphonic acid	1578770: Inhibition of human HGPRT using Prib-PP as substrate by Hanes-plot based method	ki	0.1000	uM
tetrasodium;2-amino-7-[2-(2-phosphonatoethoxymethyl)-3-(phosphonatomethoxy)propyl]-3H-pyrrolo[2,3-d]pyrimidin-4-one	1458942: Inhibition of human HGPRT using PRib-PP as the substrate by spectrophotometric method	ki	0.1000	uM
tetrasodium;2-amino-8-bromo-9-[2-(2-phosphonatoethoxymethyl)-3-(phosphonatomethoxy)propyl]-1H-purin-6-one	1458942: Inhibition of human HGPRT using PRib-PP as the substrate by spectrophotometric method	ki	0.1000	uM
tetrasodium;2-amino-9-[3-(2-phosphonatoethoxy)-2-(2-phosphonatoethoxymethyl)propyl]-1H-purin-6-one	1486339: Inhibition of N-terminal hexa-histidine-tagged human HGPRT using PRib-PP as substrate in presence of guanine by Hanes plot analysis	ki	0.1000	uM
tetrasodium;2-amino-9-[(2S)-2-[(2R)-2-hydroxy-2-phosphonatoethoxy]-3-(phosphonatomethoxy)propyl]-1H-purin-6-one	1902599: Inhibition of human HGPRT using PRib-PP as substrate by spectrophotometric assay	ki	0.1000	uM
tetrasodium;2-amino-9-[(2S)-2-(2-hydroxy-2-phosphonatoethoxy)-3-(phosphonatomethoxy)propyl]-1H-purin-6-one	1902599: Inhibition of human HGPRT using PRib-PP as substrate by spectrophotometric assay	ki	0.1000	uM
[3-[(2R,4S)-4-(2-amino-6-oxo-1H-purin-9-yl)-2-(2-phosphonoethoxymethyl)pyrrolidin-1-yl]-3-oxopropyl]phosphonic acid	2105914: Inhibition of human HGPRT by spectrophotometry	ki	0.1400	uM
3-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-(2-phosphonoethyl)amino]propanoic acid	689807: Inhibition of human HGPRT using Prib-PP as substrate by spectrophotometric assay in presence of guanine	ki	0.1500	uM
tetrasodium;2-amino-9-[[1,4-bis(2-phosphonatoethyl)piperazin-2-yl]methyl]-1H-purin-6-one	1759885: Inhibition of human HGPRT using PRib-PP as substrate by Hanes-plot based method	ki	0.1500	uM
2-[2-(6-oxo-1H-purin-9-yl)ethyl-(2-phosphonoethoxymethyl)amino]ethylphosphonic acid	1189879: Inhibition of human HGPRT	ki	0.1900	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-(2-phosphonoethyl)amino]ethylphosphonic acid	689807: Inhibition of human HGPRT using Prib-PP as substrate by spectrophotometric assay in presence of guanine	ki	0.2000	uM
disodium;2-amino-9-[2-(2-phosphonatoethylsulfinyl)ethyl]-1H-purin-6-one	1517235: Inhibition of human HGPRT using Prib-PP as substrate by Hanes-plot based method	ki	0.2000	uM
disodium;2-amino-9-[2-(2-hydroxy-2-phosphonatoethoxy)ethyl]-1H-purin-6-one	1902599: Inhibition of human HGPRT using PRib-PP as substrate by spectrophotometric assay	ki	0.2000	uM
tetrasodium;2-amino-8-bromo-9-[3-(2-phosphonatoethoxy)-2-(2-phosphonatoethoxymethyl)propyl]-1H-purin-6-one	1486339: Inhibition of N-terminal hexa-histidine-tagged human HGPRT using PRib-PP as substrate in presence of guanine by Hanes plot analysis	ki	0.2500	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethoxy]butylphosphonic acid	451291: Inhibition of human recombinant HGPRT expressed in Escherichia coli by spectrophotometric assay	ki	0.3000	uM
2-[2-(2-amino-6-oxo-1H-purin-9-yl)ethyl-(4-phosphonobutyl)amino]ethylphosphonic acid	1189879: Inhibition of human HGPRT	ki	0.3000	uM
tetrasodium;2-amino-9-[1,3-bis(2-phosphonatoethoxy)propan-2-yl]-1H-purin-6-one	1486339: Inhibition of N-terminal hexa-histidine-tagged human HGPRT using PRib-PP as substrate in presence of guanine by Hanes plot analysis	ki	0.3000	uM
tetrasodium;9-[(2R)-3-(phosphonatomethoxy)-2-(3-phosphonatopropoxy)propyl]-1H-purin-6-one	1902599: Inhibition of human HGPRT using PRib-PP as substrate by spectrophotometric assay	ki	0.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	affects cotreatment, increases mutagenesis, increases abundance, affects splicing	4
Benzo(a)pyrene	decreases reaction, affects methylation, increases expression, increases response to substance, affects cotreatment (+3 more)	4
Valproic Acid	affects cotreatment, increases expression	4
Tretinoin	decreases expression	3
4-biphenylamine	increases mutagenesis, increases response to substance, affects reaction	2
bisphenol A	decreases expression	2
sodium arsenite	decreases reaction, increases mutagenesis, increases response to substance, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Hydrogen Peroxide	increases mutagenesis	2
Nitric Oxide	increases mutagenesis	2
4-Nitroquinoline-1-oxide	increases mutagenesis	2
Styrene	increases mutagenesis, increases reaction	2
Acrylamide	increases expression, increases mutagenesis	2
aristolochic acid I	decreases expression, increases expression	1
bisphenol F	increases expression	1
napabucasin	decreases expression	1
diepoxybutane	increases mutagenesis	1
lead acetate	decreases activity	1
sodium arsenate	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases response to substance, affects cotreatment, increases mutagenesis	1
cinnamaldehyde	decreases mutagenesis	1
arsenite	affects binding, decreases reaction	1
benzo(a)pyrene 7,8-dihydrodiol	increases mutagenesis, increases reaction, decreases reaction	1
2-amino-9H-pyrido(2,3-b)indole	affects cotreatment, increases mutagenesis, increases reaction, affects binding	1
cobaltous chloride	decreases expression	1
3-amino-1-methyl-5H-pyrido(4,3-b)indole	increases mutagenesis	1
potassium bromate	increases mutagenesis	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
benzidine	affects mutagenesis, affects response to substance	1

ChEMBL screening assays

67 unique, capped per target: 52 binding, 12 functional, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1035270	Binding	Inhibition of human recombinant HGPRT at pH 8.5 by spectrophotometric assay	Inhibition of hypoxanthine-guanine phosphoribosyltransferase by acyclic nucleoside phosphonates: a new class of antimalarial therapeutics. — J Med Chem
CHEMBL4818708	ADMET	Inhibition of human HGPRT using PRib-PP as substrate by Hanes-plot based method	Nucleotide analogues containing a pyrrolidine, piperidine or piperazine ring: Synthesis and evaluation of inhibition of plasmodial and human 6-oxopurine phosphoribosyltransferases and in vitro antimalarial activity. — Eur J Med Chem
CHEMBL696682	Functional	Mutagenic activity for hypoxanthine-guanine phosphoribosyltransferase (HGPRT) in chinese hamster ovary cells at a dose of 3 ug/ml; Exp I	Synthesis, spectral analysis, and mutagenicity of 1-, 3-, and 6-nitrobenzo[a]pyrene. — J Med Chem

Cellosaurus cell lines

40 cell lines: 16 finite cell line, 9 transformed cell line, 8 induced pluripotent stem cell, 4 cancer cell line, 2 embryonic stem cell, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2448	GM01899	Transformed cell line	Male
CVCL_5T44	GM25541	Induced pluripotent stem cell	Male
CVCL_A4XM	SDQLCHi030-A	Induced pluripotent stem cell	Male
CVCL_BW14	GM23784	Finite cell line	Male
CVCL_BW15	GM23785	Finite cell line	Male
CVCL_BW16	GM23814	Finite cell line	Male
CVCL_BW20	GM23837	Finite cell line	Male
CVCL_C1CL	RPE1_HPRT1_E10	Telomerase immortalized cell line	Female
CVCL_C9YW	CEBe033-A-8	Embryonic stem cell	Male
CVCL_C9YX	CEBe033-A-9	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01751802	PHASE3	TERMINATED	Ecopipam Treatment of Self-Injurious Behavior in Subjects With Lesch-Nyhan Disease
NCT00004314	PHASE2	COMPLETED	Phase II Pilot Study of Aminoimidazole Carboxamide Riboside (AICAR), a Precursor of Purine Synthesis, for Lesch-Nyhan Disease
NCT01065558	PHASE1	COMPLETED	Safety and Tolerability of the D1 Dopamine Receptor Antagonist Ecopipam in Patients With Lesch-Nyhan Disease
NCT05548751	Not specified	UNKNOWN	Physiotherapy Assessment Based on the ICF Model in The Lesch-Nyhan Syndrome: Case Report
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.