GRHPR

glyoxylate and hydroxypyruvate reductase

Basic information

Region (hg38): 9:37422665-37436990

Previous symbols: [ "GLXR" ]

Links

ENSG00000137106 ∙ NCBI:9380 ∙ OMIM:604296 ∙ HGNC:4570 ∙ Uniprot:Q9UBQ7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary hyperoxaluria type 2 (Definitive), mode of inheritance: AR
• primary hyperoxaluria type 2 (Strong), mode of inheritance: AR
• primary hyperoxaluria type 2 (Supportive), mode of inheritance: AR
• primary hyperoxaluria type 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperoxaluria, primary, type II	AR	Renal	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	Biochemical; Renal	4321474; 2040928; 7987654; 9243228; 10484776; 11030416; 11518794; 11156702; 11135054; 11477177; 12185464; 14635115; 12897114; 15327387; 16756993; 17510093; 19296982; 20301742; 24116921

ClinVar

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

• not provided (292 variants)
• Primary hyperoxaluria, type II (193 variants)
• Nephrolithiasis/nephrocalcinosis (22 variants)
• Inborn genetic diseases (11 variants)
• not specified (6 variants)
• Primary hyperoxaluria (3 variants)
• - (2 variants)
• Nephrocalcinosis;Nephrolithiasis (1 variants)
• GRHPR-related condition (1 variants)
• Nephrolithiasis;Nephrocalcinosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRHPR 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			1	109	4	114
missense	4	11	44	8		67
nonsense	8	8				16
start loss		3				3
frameshift	23	36	2			61
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)	4	22	2			28
splice region	1	2	3	25	1	32
non coding		1	2	37	14	54
Total	39	82	54	154	18

Highest pathogenic variant AF is 0.000190

Variants in GRHPR

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

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

Position	Type	Phenotype	Significance	ClinVar
9-37422678-C-A			Benign (Jan 23, 2020)
9-37422747-G-A		GRHPR-related disorder	Likely benign (Jul 16, 2019)
9-37422747-GC-AT		Primary hyperoxaluria, type II	Likely pathogenic (Oct 14, 2021)
9-37422748-C-T		GRHPR-related disorder	Likely benign (Jul 16, 2019)
9-37422751-A-G		Primary hyperoxaluria, type II	Pathogenic/Likely pathogenic (Jul 22, 2021)
9-37422751-A-T		Primary hyperoxaluria, type II	Likely pathogenic (Mar 06, 2018)
9-37422752-T-G		Primary hyperoxaluria, type II	Likely pathogenic (Apr 06, 2017)
9-37422756-A-G			Likely benign (Jul 13, 2023)
9-37422759-G-C		Nephrolithiasis/nephrocalcinosis	Likely benign (Feb 18, 2024)
9-37422762-G-A			Likely benign (Jul 21, 2023)
9-37422763-C-T			Pathogenic (Jul 17, 2023)
9-37422764-G-A		Primary hyperoxaluria, type II	Uncertain significance (Sep 04, 2020)
9-37422766-C-T		Primary hyperoxaluria, type II • GRHPR-related disorder	Benign/Likely benign (Jan 31, 2024)
9-37422772-A-AAGGT			Pathogenic (Sep 02, 2020)
9-37422777-G-A			Likely benign (Aug 09, 2023)
9-37422783-C-T			Likely benign (Nov 09, 2023)
9-37422784-A-G		Primary hyperoxaluria, type II	Conflicting classifications of pathogenicity (Oct 09, 2020)
9-37422786-C-T			Likely benign (Jan 08, 2024)
9-37422789-C-T			Likely benign (Nov 01, 2022)
9-37422793-A-C			Uncertain significance (May 01, 2021)
9-37422794-TA-T		Primary hyperoxaluria, type II	Pathogenic (Nov 27, 2014)
9-37422798-C-G			Likely benign (Jan 10, 2024)
9-37422801-C-G			Likely benign (Nov 21, 2020)
9-37422801-C-T			Likely benign (Aug 04, 2022)
9-37422807-T-C			Likely benign (Nov 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRHPR	protein_coding	protein_coding	ENST00000318158	9	14325

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.64e-7	0.633	125606	0	142	125748	0.000565

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.739	169	198	0.852	0.0000121	2104
Missense in Polyphen		53	68.075	0.77856		724
Synonymous	-0.434	92	86.9	1.06	0.00000586	690
Loss of Function	1.06	12	16.7	0.719	8.91e-7	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000412	0.000412
Ashkenazi Jewish	0.00	0.00
East Asian	0.000598	0.000598
Finnish	0.000833	0.000832
European (Non-Finnish)	0.000736	0.000721
Middle Eastern	0.000598	0.000598
South Asian	0.000588	0.000555
Other	0.000328	0.000326

dbNSFP

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.
• Pathway: 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;Pyruvate kinase deficiency;Leigh Syndrome;Pyruvate Metabolism;Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency);Metabolism of amino acids and derivatives;Metabolism;Glyoxylate metabolism and glycine degradation (Consensus)

Intolerance Scores

• loftool: 0.332
• rvis_EVS: -0.11
• rvis_percentile_EVS: 45.36

Haploinsufficiency Scores

• pHI: 0.113
• hipred: N
• hipred_score: 0.365
• ghis: 0.493

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.955

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Grhpr
• Phenotype: homeostasis/metabolism phenotype; renal/urinary system phenotype; immune system phenotype

Gene ontology

• Biological process: excretion;cellular nitrogen compound metabolic process;dicarboxylic acid metabolic process;glyoxylate metabolic process;protein complex oligomerization;oxidation-reduction process
• Cellular component: cytoplasm;peroxisomal matrix;cytosol;extracellular exosome
• 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;protein homodimerization activity;NAD binding;NADPH binding