GMPR2

protein-coding

guanosine monophosphate reductase 2

Gene summary

This gene encodes an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of guanosine monophosphate (GMP) to inosine monophosphate (IMP). The protein also functions in the re-utilization of free intracellular bases and purine nucleosides. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

MANE transcript

NM_001002002.3

Inheritance

—

ClinVar variants

U:67

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr14:24,232,422-24,239,242

External References & Databases

Ensembl (ENSG00000100938)

Transcript & Mutation Effects

hg38 • Region Span ~6.8 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 GMPR2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 57

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001002002.3. 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			1 clinvar			1
missense			63 clinvar			63
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	67	0	0	67

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 127 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001002002.3	RefSeq	NP_001002002.1	9	MANE Select
ENST00000399440.7	Ensembl	ENSP00000382369.2	9	MANE Select
NM_001002000.3	RefSeq	NP_001002000.1	9	Standard
NM_001002001.3	RefSeq	NP_001002001.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Purine metabolism - Homo sapiens (human)
Metabolism of nucleotides
Metabolism
Nucleotide salvage
Purine salvage

Biological Process

purine nucleobase metabolic process
purine ribonucleotide interconversion
purine-containing compound salvage
GMP metabolic process
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: ENST00000420554
Coding exons: 9
Length: 6821
Individuals with no LoFs: 124731
Homozygous LoFs: 0
Heterozygous LoFs: 95
Defined: 124826
p: 0.000381

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.800	177	210	0.845	0.0000106	2399
Missense (PolyPhen)		65	78.441	0.82865		912
Synonymous	-0.261	78	75.1	1.04	0.00000383	726
Loss of Function	0.705	14	17.1	0.816	8.50e-7	213

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00019	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00039	0.00039	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00058	0.00058	rare
South Asian	0.000098	0.000098	rare
Other	0.00049	0.00049	rare

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 (PubMed:12009299, PubMed:12669231, PubMed:16359702, PubMed:22037469). Plays a role in modulating cellular differentiation (PubMed:12669231). {ECO:0000255|HAMAP- Rule:MF_03195, ECO:0000269|PubMed:12009299, ECO:0000269|PubMed:12669231, ECO:0000269|PubMed:16359702, ECO:0000269|PubMed:22037469}.;

Recessive Scores

pRec: 0.249

Intolerance Scores

LoFtool: 0.454
RVIS EVS: -0.18
RVIS percentile EVS: 40.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.997

Gene Damage Prediction

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