HPRT1

hypoxanthine phosphoribosyltransferase 1

Basic information

Region (hg38): X:134460165-134520513

Previous symbols: [ "HPRT" ]

Links

ENSG00000165704 ∙ NCBI:3251 ∙ OMIM:308000 ∙ HGNC:5157 ∙ Uniprot:P00492 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Lesch-Nyhan syndrome (Supportive), mode of inheritance: XL
• hypoxanthine guanine phosphoribosyltransferase partial deficiency (Supportive), mode of inheritance: XL
• Lesch-Nyhan syndrome (Strong), mode of inheritance: XL
• Lesch-Nyhan syndrome (Definitive), mode of inheritance: XL
• hypoxanthine guanine phosphoribosyltransferase partial deficiency (Strong), mode of inheritance: XL
• Lesch-Nyhan syndrome (Definitive), mode of inheritance: XL
• hypoxanthine guanine phosphoribosyltransferase partial deficiency (Definitive), mode of inheritance: XLR
• Lesch-Nyhan syndrome (Definitive), mode of inheritance: XLR
• Lesch-Nyhan syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperuricemia, HPRT related (Kelley-Seegmiller syndrome); Lesch-Nyhan syndrome	XL	Biochemical; Renal	Treatments related to uric acid overproduction, such as alkalinization and allopurinol, can be effective in order to prevent and treat sequelae such as renal dysfunction and gouty arthritis	Biochemical; Hematologic; Musculoskeletal; Neurologic; Renal	14142409; 4291947; 4322125; 3600927; 10657589; 11891689; 20301328; 20558399; 31182398
In Lesch-Nyhan syndrome, an allelic condition, as in Kelley-Seegmiller syndrome, control of uric acid production can be effective to reduce sequelae, but does not affect Neurological manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HPRT1 gene.

• Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome (20 variants)
• not provided (14 variants)
• Lesch-Nyhan syndrome (12 variants)
• Lesch-Nyhan syndrome;Partial hypoxanthine-guanine phosphoribosyltransferase deficiency (6 variants)
• HPRT1-related disorder (2 variants)
• Lesch-nyhan syndrome, neurologic variant (1 variants)
• HPRT CHERMSIDE (1 variants)
• HPRT NEW HAVEN (1 variants)
• Microcephaly (1 variants)
• Partial hypoxanthine-guanine phosphoribosyltransferase deficiency (1 variants)
• HPRT FUJIMI (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HPRT1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				23	5	28
missense	12	11	28	1		52
nonsense	7	1	1			9
start loss	1	1				2
frameshift	12		1			13
inframe indel			1			1
splice donor/acceptor (+/-2bp)	9	4				13
splice region		1	3	9	5	18
non coding		1		41	8	50
Total	41	18	31	65	13

Variants in HPRT1

This is a list of pathogenic ClinVar variants found in the HPRT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-134460299-GGCCGGCTCCGTTA-G		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome • Partial hypoxanthine-guanine phosphoribosyltransferase deficiency	Likely pathogenic (May 20, 2020)
X-134460312-A-G		Lesch-Nyhan syndrome	Pathogenic (Jul 14, 2022)
X-134460318-ACCCGCAG-A		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Pathogenic (Dec 19, 2021)
X-134460324-AGCCCTGGCGTCGTGGTGAGCAGCTCGGCCTGCCG-A		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Pathogenic (Dec 24, 2019)
X-134460332-C-A		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Likely benign (Jul 16, 2023)
X-134460332-C-T		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Likely benign (Sep 21, 2023)
X-134460333-G-A		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Uncertain significance (Aug 30, 2023)
X-134460334-T-G		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Uncertain significance (Sep 19, 2023)
X-134460335-C-G		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Likely benign (Apr 17, 2023)
X-134460345-A-G		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Likely benign (Dec 30, 2023)
X-134460350-G-A		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Likely benign (Sep 04, 2023)
X-134460357-C-G		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Likely benign (Sep 29, 2023)
X-134460357-C-T		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Likely benign (Nov 01, 2023)
X-134473151-A-G			Likely benign (May 15, 2021)
X-134473340-A-G		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Likely benign (Aug 10, 2023)
X-134473344-A-G		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Likely benign (Nov 28, 2023)
X-134473344-AT-A		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Benign (Jan 31, 2024)
X-134473346-A-G		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Likely benign (Oct 19, 2023)
X-134473357-A-G		Lesch-Nyhan syndrome	Likely pathogenic (Nov 24, 2023)
X-134473357-A-T		Lesch-Nyhan syndrome • HPRT1-related disorder	Pathogenic (Nov 06, 2023)
X-134473365-G-T		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Uncertain significance (May 06, 2022)
X-134473371-GA-G		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Pathogenic (Dec 28, 2023)
X-134473377-G-A		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency • HPRT URANGAN	Pathogenic; other (May 12, 2011)
X-134473378-G-T		Lesch-Nyhan syndrome	Pathogenic (Jan 06, 2017)
X-134473384-A-G		Partial hypoxanthine-guanine phosphoribosyltransferase deficiency;Lesch-Nyhan syndrome	Uncertain significance (May 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HPRT1	protein_coding	protein_coding	ENST00000298556	9	60361

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.937	0.0625	122217	0	1	122218	0.00000409

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.32	20	77.4	0.258	0.00000524	1444
Missense in Polyphen		2	19.147	0.10445		395
Synonymous	1.62	15	25.4	0.591	0.00000167	397
Loss of Function	2.75	0	8.79	0.00	6.70e-7	169

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000372	0.0000372
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Disease: DISEASE: Lesch-Nyhan syndrome (LNS) [MIM:300322]: Characterized by complete lack of enzymatic activity that results in hyperuricemia, choreoathetosis, mental retardation, and compulsive self- mutilation. {ECO:0000269|PubMed:15571223, ECO:0000269|PubMed:17027311, ECO:0000269|PubMed:20544509, ECO:0000269|PubMed:2071157, ECO:0000269|PubMed:2246854, ECO:0000269|PubMed:2347587, ECO:0000269|PubMed:2358296, ECO:0000269|PubMed:24940672, ECO:0000269|PubMed:2572141, ECO:0000269|PubMed:2910902, ECO:0000269|PubMed:3265398, ECO:0000269|PubMed:3384338, ECO:0000269|PubMed:6853716, ECO:0000269|PubMed:7627191, ECO:0000269|PubMed:9452051}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Gout HPRT-related (GOUT-HPRT) [MIM:300323]: Characterized by partial enzyme activity and hyperuricemia. {ECO:0000269|PubMed:15571223, ECO:0000269|PubMed:17027311, ECO:0000269|PubMed:20544509, ECO:0000269|PubMed:24940672, ECO:0000269|PubMed:2896620, ECO:0000269|PubMed:2909537, ECO:0000269|PubMed:3198771, ECO:0000269|PubMed:3358423, ECO:0000269|PubMed:6572373, ECO:0000269|PubMed:6706936, ECO:0000269|PubMed:6853490, ECO:0000269|PubMed:7987318}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Drug metabolism - other enzymes - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics;Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Thioguanine Metabolism Pathway;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Mercaptopurine Metabolism Pathway;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Mesodermal Commitment Pathway;Nucleotide Metabolism;Purine metabolism;Metabolism of nucleotides;Metabolism;guanine and guanosine salvage;Nucleotide salvage;Purine salvage;Purine nucleotides nucleosides metabolism;superpathway of purine nucleotide salvage;adenine and adenosine salvage III (Consensus)

Recessive Scores

• pRec: 0.941

Intolerance Scores

• loftool: 0.128
• rvis_EVS: -0.01
• rvis_percentile_EVS: 52.85

Haploinsufficiency Scores

• pHI: 0.655
• hipred: Y
• hipred_score: 0.825
• ghis: 0.659

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.445

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Low	Medium

Mouse Genome Informatics

• Gene name: Hprt
• Phenotype: immune system phenotype; skeleton phenotype; renal/urinary system phenotype; no phenotypic analysis (no description of morphological, physiological or behavioral information presented); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; pigmentation phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: T cell mediated cytotoxicity;response to amphetamine;purine nucleotide biosynthetic process;purine ribonucleoside salvage;adenine salvage;guanine salvage;grooming behavior;locomotory behavior;striatum development;cerebral cortex neuron differentiation;central nervous system neuron development;GMP salvage;IMP salvage;dopamine metabolic process;purine-containing compound salvage;hypoxanthine salvage;positive regulation of dopamine metabolic process;GMP catabolic process;IMP metabolic process;hypoxanthine metabolic process;lymphocyte proliferation;dendrite morphogenesis;protein homotetramerization
• Cellular component: cytoplasm;cytosol;extracellular exosome
• Molecular function: nucleotide binding;magnesium ion binding;hypoxanthine phosphoribosyltransferase activity;protein binding;identical protein binding;protein homodimerization activity;guanine phosphoribosyltransferase activity