PFAS

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

Basic information

Region (hg38): 17:8247618-8270491

Links

ENSG00000178921 ∙ NCBI:5198 ∙ OMIM:602133 ∙ HGNC:8863 ∙ Uniprot:O15067 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PFAS gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PFAS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense			67	6	3	76
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	67	8	3

Variants in PFAS

This is a list of pathogenic ClinVar variants found in the PFAS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-8247845-A-C			Benign (Feb 24, 2019)
17-8247860-G-A			Benign (Nov 10, 2018)
17-8247987-G-T		Dyskeratosis congenita	Likely benign (May 17, 2022)
17-8247989-A-T		Dyskeratosis congenita	Likely benign (Nov 07, 2023)
17-8247991-T-C		Dyskeratosis congenita	Likely benign (Jun 16, 2022)
17-8247995-A-C		Dyskeratosis congenita	Likely benign (Jul 08, 2019)
17-8247995-A-G		Dyskeratosis congenita	Likely benign (Aug 01, 2023)
17-8247997-C-A		Dyskeratosis congenita	Likely benign (Dec 22, 2023)
17-8247997-C-T		Dyskeratosis congenita	Likely benign (Apr 10, 2023)
17-8247998-A-G		Dyskeratosis congenita	Uncertain significance (Mar 19, 2022)
17-8248000-T-C		Dyskeratosis congenita	Uncertain significance (Aug 16, 2022)
17-8248002-A-C		Dyskeratosis congenita	Likely pathogenic (Feb 18, 2021)
17-8248004-G-A		Dyskeratosis congenita • Cerebroretinal microangiopathy with calcifications and cysts 1	Uncertain significance (Sep 24, 2021)
17-8248005-G-T		Dyskeratosis congenita	Uncertain significance (Mar 09, 2020)
17-8248007-G-A		Dyskeratosis congenita	Likely benign (Nov 18, 2023)
17-8248008-G-A		Dyskeratosis congenita	Uncertain significance (Aug 24, 2023)
17-8248008-G-C		Dyskeratosis congenita	Uncertain significance (Aug 24, 2019)
17-8248009-A-T		Dyskeratosis congenita	Uncertain significance (Oct 14, 2020)
17-8248010-A-G		Dyskeratosis congenita	Likely benign (Jun 13, 2022)
17-8248010-A-T		Dyskeratosis congenita	Likely benign (Aug 14, 2023)
17-8248011-G-A		Dyskeratosis congenita	Uncertain significance (Jul 19, 2022)
17-8248011-G-C		Dyskeratosis congenita	Uncertain significance (Mar 04, 2022)
17-8248011-G-T		Dyskeratosis congenita	Uncertain significance (Jul 11, 2022)
17-8248012-G-A		Dyskeratosis congenita	Uncertain significance (Mar 25, 2022)
17-8248013-G-A		Dyskeratosis congenita	Likely benign (Oct 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PFAS	protein_coding	protein_coding	ENST00000314666	27	22874

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.85e-18	0.998	125626	0	122	125748	0.000485

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.961	756	834	0.906	0.0000528	8566
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000692	0.000689
Ashkenazi Jewish	0.000619	0.000595
East Asian	0.000707	0.000653
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000606	0.000598
Middle Eastern	0.000707	0.000653
South Asian	0.000361	0.000359
Other	0.000816	0.000815

dbNSFP

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}.
• Pathway: Purine metabolism - Homo sapiens (human);Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Metabolism of nucleotides;Metabolism;Nucleobase biosynthesis;Purine nucleotides nucleosides metabolism;Purine ribonucleoside monophosphate biosynthesis;5-aminoimidazole ribonucleotide biosynthesis;purine nucleotides <i>de novo</i> biosynthesis (Consensus)

Intolerance Scores

• loftool: 0.865
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.22

Haploinsufficiency Scores

• pHI: 0.786
• hipred: Y
• hipred_score: 0.578
• ghis: 0.650

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pfas
• Phenotype: hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; craniofacial phenotype; vision/eye phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: 'de novo' IMP biosynthetic process;glutamine metabolic process;purine ribonucleoside monophosphate biosynthetic process;response to drug;anterior head development
• Cellular component: cytoplasm;cytosol;extracellular exosome
• Molecular function: phosphoribosylformylglycinamidine synthase activity;ATP binding;metal ion binding