PFAS

protein-coding

phosphoribosylformylglycinamidine synthase, the group of Glutamine amidotransferase class 1 domain containing|Purinosome

Gene summary

Purines are necessary for many cellular processes, including DNA replication, transcription, and energy metabolism. Ten enzymatic steps are required to synthesize inosine monophosphate (IMP) in the de novo pathway of purine biosynthesis. The enzyme encoded by this gene catalyzes the fourth step of IMP biosynthesis. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012393.3

Inheritance

—

ClinVar variants

P:3U:189B:12

Top phenotype

Phosphoribosylformylglycineamidine synthase deficiency

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr17:8,247,618-8,270,491

External References & Databases

Ensembl (ENSG00000178921)

Transcript & Mutation Effects

hg38 • Region Span ~22.9 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 PFAS variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 180

not providedTotal: 8

Phosphoribosylformylglycineamidine synthase deficiencyTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012393.3. 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			4 clinvar	2 clinvar		6
missense		2 clinvar	180 clinvar	7 clinvar	3 clinvar	192
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar		5 clinvar			6
Total	1	2	189	9	3	204

Highest pathogenic variant AF is 0.000400853

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012393.3	RefSeq	NP_036525.1	27	MANE Select
ENST00000314666.11	Ensembl	ENSP00000313490.6	27	MANE Select
ENST00000546020.2	Ensembl	ENSP00000443244.2	7	Standard
ENST00000578979.5	Ensembl	ENSP00000463103.1	3	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

'de novo' IMP biosynthetic process
glutamine metabolic process
purine ribonucleoside monophosphate biosynthetic process
response to drug
anterior head development

Molecular Function

phosphoribosylformylglycinamidine synthase activity
ATP binding
metal ion binding

Cellular Component

cytoplasm
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314666
Coding exons: 27
Length: 22874
Individuals with no LoFs: 125626
Homozygous LoFs: 0
Heterozygous LoFs: 122
Defined: 125748
p: 0.000485

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.961	756	834	0.906	0.0000528	8566
Missense (PolyPhen)		248	315.21	0.78679		3297
Synonymous	-0.525	357	345	1.04	0.0000215	2891
Loss of Function	3.05	38	64.4	0.590	0.00000352	656

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0.00062	0.00060	rare
East Asian	0.00071	0.00065	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00061	0.00060	rare
South Asian	0.00036	0.00036	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Phosphoribosylformylglycinamidine synthase involved in the purines biosynthetic pathway. Catalyzes the ATP-dependent conversion of formylglycinamide ribonucleotide (FGAR) and glutamine to yield formylglycinamidine ribonucleotide (FGAM) and glutamate (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.865
RVIS EVS: -0.51
RVIS percentile EVS: 21.22

Essentials

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

Gene Damage Prediction

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