GRHPR

Chr 9AR

glyoxylate and hydroxypyruvate reductase

Also known as: GLXR, GLYD, PH2

NCBI Gene: 9380ENSG00000137106UniProt: Q9UBQ7

This gene encodes an enzyme with hydroxypyruvate reductase, glyoxylate reductase, and D-glycerate dehydrogenase enzymatic activities. The enzyme has widespread tissue expression and has a role in metabolism. Type II hyperoxaluria is caused by mutations in this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Hyperoxaluria, primary, type IIMIM #260000
AR
UniProtHyperoxaluria primary 2
723
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GRHPR
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
723 total variants — no pathogenic classifications of 723 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.17LOEUF
pLI 0.000
Z-score 1.06
OE 0.72 (0.46–1.17)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.74Z-score
OE missense 0.85 (0.75–0.97)
169 obs / 198.3 exp
Tolerant

Mild missense constraint

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.0.72 (0.46–1.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.75–0.97)
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.1.06
0≤1.21.6
LoF obs/exp: 12 / 16.7Missense obs/exp: 169 / 198.3Syn Z: -0.43

ClinVar Variant Classifications

723 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

GRHPR · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hyperoxaluria, primary, type II

MIM #260000

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria.
Hopp K et al.·J Am Soc Nephrol
2015
Integrating single-nucleus sequence profiling to reveal the transcriptional dynamics of Alzheimer's disease, Parkinson's disease, and multiple sclerosis.
Fan LY et al.·J Transl Med
2023
Prevalence and characteristics of genetic disease in adult kidney stone formers.
Anderegg MA et al.·Nephrol Dial Transplant
2024
Folding Defects Leading to Primary Hyperoxaluria.
Oppici E et al.·Handb Exp Pharmacol
2018Review
[The Hyperoxalurias].
Marangella M et al.·G Ital Nefrol
2016
Genetic assessment in primary hyperoxaluria: why it matters.
Mandrile G et al.·Pediatr Nephrol
2023Review
Clinical and molecular characterization of primary hyperoxaluria in Egypt.
Soliman NA et al.·Sci Rep
2022
ENDOCRINE MANIFESTATIONS OF PRIMARY HYPEROXALURIA.
Murad S et al.·Endocr Pract
2017Review
Identification of a novel GRHPR mutation in primary hyperoxaluria type 2 and establishment of patient-derived iPSC line.
Yan X et al.·Hum Cell
2025
Genotype and Phenotype Characteristics of Chinese Pediatric Patients with Primary Hyperoxaluria.
Ge Y et al.·Hum Mutat
2023Cohort
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