GMPR

protein-coding

guanosine monophosphate reductase

Gene summary

This gene encodes an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of GMP to IMP. The protein also functions in the re-utilization of free intracellular bases and purine nucleosides.[provided by RefSeq, Oct 2009]

MANE transcript

NM_006877.4

Inheritance

—

ClinVar variants

U:63B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr6:16,238,587-16,295,549

External References & Databases

Ensembl (ENSG00000137198)

Transcript & Mutation Effects

hg38 • Region Span ~57.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GMPR variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 55

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006877.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					2 clinvar	2
missense			57 clinvar		1 clinvar	58
nonsense						0
start loss						0
frameshift				1 clinvar	1 clinvar	2
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	63	1	4	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006877.4	RefSeq	NP_006868.3	9	MANE Select
ENST00000259727.5	Ensembl	ENSP00000259727.4	9	MANE Select
ENST00000864757.1	Ensembl	ENSP00000534816.1	9	Standard
ENST00000864757.2	Ensembl	ENSP00000534816.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Purine metabolism - Homo sapiens (human)
Purine Nucleoside Phosphorylase Deficiency
Mercaptopurine Action Pathway
Azathioprine Action Pathway
Xanthine Dehydrogenase Deficiency (Xanthinuria)

Biological Process

purine nucleobase metabolic process
response to cold
purine ribonucleotide interconversion
purine-containing compound salvage
oxidation-reduction process

Molecular Function

GMP reductase activity
metal ion binding

Cellular Component

cytosol
GMP reductase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000259727
Coding exons: 9
Length: 56970
Individuals with no LoFs: 124906
Homozygous LoFs: 7
Heterozygous LoFs: 835
Defined: 125748
p: 0.00335

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.124	198	203	0.976	0.0000118	2249
Missense (PolyPhen)		92	95.911	0.95922		1071
Synonymous	-0.575	89	82.4	1.08	0.00000552	688
Loss of Function	1.39	10	16.0	0.624	7.55e-7	199

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.025	0.019	notable
Finnish	0.0037	0.0037	notable
European (Non-Finnish)	0.0031	0.0031	notable
South Asian	0.00066	0.00059	rare
Other	0.0044	0.0042	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides. {ECO:0000255|HAMAP-Rule:MF_03195}.;

Recessive Scores

pRec: 0.219

Intolerance Scores

LoFtool: 0.480
RVIS EVS: -0.31
RVIS percentile EVS: 31.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.882

Gene Damage Prediction

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