PPAT

protein-coding

phosphoribosyl pyrophosphate amidotransferase, the group of Purinosome

Gene summary

The protein encoded by this gene is a member of the purine/pyrimidine phosphoribosyltransferase family. It is a regulatory allosteric enzyme that catalyzes the first step of de novo purine nucleotide biosythetic pathway. This gene and PAICS/AIRC gene, a bifunctional enzyme catalyzing steps six and seven of this pathway, are located in close proximity on chromosome 4, and divergently transcribed from an intergenic region. [provided by RefSeq, Mar 2011]

MANE transcript

NM_002703.5

Inheritance

—

ClinVar variants

U:31B:2

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr4:56,393,362-56,435,615

External References & Databases

Ensembl (ENSG00000128059)

Transcript & Mutation Effects

hg38 • Region Span ~42.3 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 PPAT variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 27

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002703.5. 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			1 clinvar			1
missense			29 clinvar	2 clinvar		31
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	31	2	0	33

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002703.5	RefSeq	NP_002694.3	11	MANE Select
ENST00000264220.6	Ensembl	ENSP00000264220.2	11	MANE Select
ENST00000507724.1	Ensembl	ENSP00000425119.1	3	Standard
ENST00000510643.5	Ensembl	ENSP00000423781.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
Alanine, aspartate and glutamate metabolism - Homo sapiens (human)
Purine metabolism - Homo sapiens (human)
Fluoropyrimidine Pathway, Pharmacokinetics
Methotrexate Pathway (Cancer Cell), Pharmacodynamics

Biological Process

G1/S transition of mitotic cell cycle
kidney development
purine nucleotide biosynthetic process
'de novo' IMP biosynthetic process
glutamine catabolic process

Molecular Function

amidophosphoribosyltransferase activity
metal ion binding
4 iron, 4 sulfur cluster binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264220
Coding exons: 11
Length: 42254
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125746
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.06	137	281	0.487	0.0000140	3349
Missense (PolyPhen)		35	120.35	0.29082		1391
Synonymous	1.66	77	97.9	0.786	0.00000487	1009
Loss of Function	4.20	3	26.2	0.115	0.00000134	332

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.379

Intolerance Scores

LoFtool: 0.216
RVIS EVS: -0.01
RVIS percentile EVS: 53.51

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.995

Gene Damage Prediction

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