GeneBe

GRHPR

protein-coding

glyoxylate and hydroxypyruvate reductase

Gene summary

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]

Previous symbols:
  • GLXR

MANE transcript

NM_012203.2

Inheritance

AR

ClinVar variants

P:176U:126B:171

Top phenotype

Hyperoxaluria, primary, type II

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr9:37,422,666-37,436,990

External References & Databases

Ensembl (ENSG00000137106)NCBI Gene (9380)OMIM (604296)HGNC:4570GenCCUniProt (Q9UBQ7)AlphaFoldClinVar (GRHPR)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~14.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

primary hyperoxaluria type 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009824

Submitter: Natera

primary hyperoxaluria type 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009824

Submitter: Ambry Genetics

primary hyperoxaluria type 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009824

Submitter: Myriad Women's Health

primary hyperoxaluria type 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009824

Submitter: Labcorp Genetics (formerly Invitae)

primary hyperoxaluria type 2SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009824

Submitter: Orphanet

primary hyperoxaluria type 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009824

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Hyperoxaluria, primary, type IIAR

Manifestation: Biochemical; Renal

Intervention: Renal

Rationale: Fluid intake and medical management (eg, orthophosphate, potassium citrate, magnesium) to prevent calcium oxalate crystallization can be effective; Temporary dialysis for ESRD, followed by transplantation may be required; Surveillance of renal function and related parameters may be effective; Dehydration and excessive intake of oxalate-rich foods should be avoided

Refs: 4321474; 2040928; 7987654; 9243228; 10484776; 11030416; 11518794; 11156702; 11135054; 11477177; 12185464; 14635115; 12897114; 15327387; 16756993; 17510093; 19296982; 20301742; 24116921Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GRHPR variants in ClinVar

10 Conditions Cataloged
not providedTotal: 408
Primary hyperoxaluria, type IITotal: 287
Nephrolithiasis/nephrocalcinosisTotal: 82
not specifiedTotal: 21
GRHPR-related disorderTotal: 21
GRHPR-related disordersTotal: 8
Primary hyperoxaluriaTotal: 3
NephrocalcinosisTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012203.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
5
clinvar
153
clinvar
3
clinvar
 161
missense
4
clinvar
23
clinvar
115
clinvar
15
clinvar
 157
nonsense
11
clinvar
10
clinvar
 21
start loss
1
clinvar
2
clinvar
 3
frameshift
40
clinvar
50
clinvar
5
clinvar
 95
splice donor/acceptor (+/-2bp)
7
clinvar
28
clinvar
1
clinvar
 36
Total631131261683473

Highest pathogenic variant AF is 0.0004965083

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 88 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_012203.2RefSeqNP_036335.19MANE Select
ENST00000318158.11EnsemblENSP00000313432.69MANE Select
ENST00000494290.1EnsemblENSP00000432021.12Standard
ENST00000607784.1EnsemblENSP00000475569.19Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Pyruvate metabolism - Homo sapiens (human)
  • Glycine, serine and threonine metabolism - Homo sapiens (human)
  • Glyoxylate and dicarboxylate metabolism - Homo sapiens (human)
  • Pyruvate Dehydrogenase Complex Deficiency
  • Primary hyperoxaluria II, PH2

Biological Process

  • excretion
  • cellular nitrogen compound metabolic process
  • dicarboxylic acid metabolic process
  • glyoxylate metabolic process
  • protein complex oligomerization

Molecular Function

  • glycerate dehydrogenase activity
  • oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
  • hydroxypyruvate reductase activity
  • glyoxylate reductase (NADP) activity
  • carboxylic acid binding

Cellular Component

  • cytoplasm
  • peroxisomal matrix
  • cytosol
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000318158
Coding exons
9
Length
14325
Individuals with no LoFs
125606
Homozygous LoFs
0
Heterozygous LoFs
142
Defined
125748
p
0.000565
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.7391691980.8520.00001212104
Missense (PolyPhen)5368.0750.77856724
Synonymous-0.4349286.91.060.00000586690
Loss of Function1.061216.70.7198.91e-7181

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.000290.00029rare
Ashkenazi Jewish00.0absent
East Asian0.000600.00060rare
Finnish0.000830.00083rare
European (Non-Finnish)0.000740.00072rare
South Asian0.000590.00056rare
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities. Reduces hydroxypyruvate to D-glycerate, glyoxylate to glycolate oxidizes D-glycerate to hydroxypyruvate.;

Intolerance Scores

LoFtool
0.332
RVIS EVS
-0.11
RVIS percentile EVS
45.36

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.955

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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