HPRT1

Chr XXLR

hypoxanthine phosphoribosyltransferase 1

Also known as: HGPRT, HPRT

NCBI Gene: 3251ENSG00000165704UniProt: P00492OMIM: 308000

The protein catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate, playing a central role in purine nucleotide generation through the purine salvage pathway. Mutations cause Lesch-Nyhan syndrome (characterized by neurologic dysfunction, cognitive impairment, and self-injurious behavior) or HPRT-related hyperuricemia with gout, following X-linked recessive inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.94, LOEUF 0.34), reflecting its essential cellular function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.342 OMIM phenotypes
Clinical Summary— HPRT1
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Gene-Disease Validity (ClinGen)
Lesch-Nyhan syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.
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ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 26 VUS of 100 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
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
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
LoF OE0.00 (0.00–0.34)
0≤0.351.4
Missense OE0.26 (0.18–0.38)
0≤0.61.4
Synonymous OE0.59
0≤1.21.6
LoF obs/exp: 0 / 8.8Missense obs/exp: 20 / 77.4Syn Z: 1.62
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveHPRT1-related Lesch-Nyhan syndromeLOFXLR
DN
0.2997th %ile
GOF
0.3689th %ile
LOF
0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 29% of P/LP variants are LoF · LOEUF 0.34

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic10
VUS26
Likely Benign7
7
Pathogenic
10
Likely Pathogenic
26
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
3
0
7
Likely Pathogenic
2
6
2
0
10
VUS
2
17
6
1
26
Likely Benign
0
0
2
5
7
Benign
0
0
0
0
0
Total72413650

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients