PRPS2

protein-coding

phosphoribosyl pyrophosphate synthetase 2

Gene summary

This gene encodes a phosphoribosyl pyrophosphate synthetase that plays a central role in the synthesis of purines and pyrimidines. The encoded protein catalyzes the synthesis of 5-phosphoribosyl 1-pyrophosphate from ATP and D-ribose 5-phosphate. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

MANE transcript

NM_002765.5

Inheritance

—

ClinVar variants

U:68

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:12,791,355-12,824,222

External References & Databases

Ensembl (ENSG00000101911)

Transcript & Mutation Effects

hg38 • Region Span ~32.9 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 PRPS2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002765.5. 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			14 clinvar			14
missense			32 clinvar			32
nonsense			7 clinvar			7
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			15 clinvar			15
Total	0	0	68	0	0	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002765.5	RefSeq	NP_002756.1	7	MANE Select
ENST00000380668.10	Ensembl	ENSP00000370043.5	7	MANE Select
NM_001039091.3	RefSeq	NP_001034180.1	7	Standard
ENST00000380663.7	Ensembl	ENSP00000370038.3	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Purine metabolism - Homo sapiens (human)
Pentose phosphate pathway - Homo sapiens (human)
Nucleotide Metabolism
Pentose phosphate pathway (hexose monophosphate shunt)
Metabolism of carbohydrates

Biological Process

5-phosphoribose 1-diphosphate biosynthetic process
nucleobase-containing compound metabolic process
purine nucleotide biosynthetic process
AMP biosynthetic process
nucleoside metabolic process

Molecular Function

magnesium ion binding
ribose phosphate diphosphokinase activity
protein binding
ATP binding
AMP binding

Cellular Component

ribose phosphate diphosphokinase complex
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398491
Coding exons: 7
Length: 32868
Individuals with no LoFs: 123049
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 123050
p: 0.00000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.05	39	141	0.277	0.0000116	2116
Missense (PolyPhen)		3	35.846	0.083691		615
Synonymous	0.462	58	62.6	0.926	0.00000595	638
Loss of Function	2.73	0	8.71	0.00	6.24e-7	156

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000073	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.;

Recessive Scores

pRec: 0.225

Intolerance Scores

LoFtool: 0.0654
RVIS EVS: -0.27
RVIS percentile EVS: 33.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.966

Gene Damage Prediction

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