HPRT1

Chr X

hypoxanthine phosphoribosyltransferase 1

Also known as: HGPRT, HPRT

NCBI Gene: 3251ENSG00000165704UniProt: P00492

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.[provided by RefSeq, Jun 2009]

Primary Disease Associations & Inheritance

UniProtLesch-Nyhan syndrome
UniProtHyperuricemia, HPRT-related
372
ClinVar variants
198
Pathogenic / LP
0.94
pLI score· haploinsufficient
0
Active trials
Clinical Summary— HPRT1
🧬
Gene-Disease Validity (ClinGen)
Lesch-Nyhan syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
198 Pathogenic / Likely Pathogenic· 67 VUS of 372 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.34LOEUF
pLI 0.937
Z-score 2.75
OE 0.00 (0.00–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.32Z-score
OE missense 0.26 (0.18–0.38)
20 obs / 77.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.26 (0.18–0.38)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.59
0≤1.21.6
LoF obs/exp: 0 / 8.8Missense obs/exp: 20 / 77.4Syn Z: 1.62

ClinVar Variant Classifications

372 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic166
Likely Pathogenic32
VUS67
Likely Benign82
Benign21
Conflicting4
166
Pathogenic
32
Likely Pathogenic
67
VUS
82
Likely Benign
21
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
19
119
0
166
Likely Pathogenic
8
18
6
0
32
VUS
0
45
21
1
67
Likely Benign
0
1
53
28
82
Benign
0
0
16
5
21
Conflicting
—4
Total368321534372

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HPRT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

HPRT1-related Lesch-Nyhan syndrome

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — HPRT1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Discovering functionally important sites in proteins.
Cagiada M et al.·Nat Commun
2023Functional
Prognostic significance and immunological role of HPRT1 in human cancers.
Lu Y et al.·Biomol Biomed
2024
Synthetic reversed sequences reveal default genomic states.
Camellato BR et al.·Nature
2024
Genotypic and phenotypic spectrum in attenuated variants of Lesch-Nyhan disease.
Fu R et al.·Mol Genet Metab
2014Review
Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder.
Fu R et al.·Brain
2014Review
PI3K/ c-Myc/AFF4 axis promotes pancreatic tumorigenesis through fueling nucleotide metabolism.
Ni C et al.·Int J Biol Sci
2023
[Analysis of HPRT1 gene variant and prenatal diagnosis for a Chinese pedigree with Lesch-Nyhan syndrome but no specimen from affected probands].
Tong M et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2022
Overexpression of HPRT1 is associated with poor prognosis in head and neck squamous cell carcinoma.
Ahmadi M et al.·FEBS Open Bio
2021
Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome.
Torres RJ et al.·Orphanet J Rare Dis
2007Review
Unapparent hypoxanthine-guanine phosphoribosyltransferase deficiency.
Torres RJ et al.·Clin Chim Acta
2017Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools