FPGS

folylpolyglutamate synthase

Basic information

Region (hg38): 9:127794597-127814494

Links

ENSG00000136877 ∙ NCBI:2356 ∙ OMIM:136510 ∙ HGNC:3824 ∙ Uniprot:Q05932 ∙ 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 FPGS gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FPGS 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						0
missense			21	1	1	23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	21	1	1

Variants in FPGS

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

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

Position	Type	Phenotype	Significance	ClinVar
9-127802935-C-T		not specified	Uncertain significance (May 06, 2022)
9-127802937-C-T		not specified	Uncertain significance (Jan 23, 2023)
9-127802943-C-T		not specified	Uncertain significance (Feb 28, 2024)
9-127802952-G-T		not specified	Uncertain significance (Sep 11, 2024)
9-127802979-G-C		not specified	Likely benign (Aug 19, 2024)
9-127802988-A-G			Benign (Oct 29, 2020)
9-127803001-T-G		not specified	Uncertain significance (Jul 14, 2021)
9-127803012-C-T		not specified	Uncertain significance (Oct 27, 2022)
9-127803013-G-A		not specified	Uncertain significance (Aug 17, 2021)
9-127804295-G-A		not specified	Uncertain significance (Jun 21, 2023)
9-127804349-A-C		not specified	Uncertain significance (Dec 09, 2023)
9-127804382-T-C		not specified	Uncertain significance (Jan 30, 2024)
9-127804639-T-A		not specified	Uncertain significance (Nov 13, 2024)
9-127804655-C-T		not specified	Uncertain significance (Mar 03, 2022)
9-127804688-C-T		not specified	Uncertain significance (Jun 05, 2024)
9-127807242-C-T		not specified	Uncertain significance (Nov 24, 2024)
9-127807269-G-A		not specified	Uncertain significance (Dec 03, 2024)
9-127807275-C-T		not specified	Uncertain significance (Apr 12, 2024)
9-127807443-T-C		not specified	Uncertain significance (Oct 22, 2024)
9-127808301-A-G		not specified	Uncertain significance (Oct 13, 2023)
9-127808581-G-A		not specified	Uncertain significance (Aug 04, 2024)
9-127808610-C-G		not specified	Uncertain significance (Nov 25, 2024)
9-127808825-G-C		not specified	Uncertain significance (Jan 17, 2024)
9-127808836-T-C		not specified	Uncertain significance (Feb 06, 2024)
9-127809726-G-A		not specified	Uncertain significance (Oct 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FPGS	protein_coding	protein_coding	ENST00000373247	15	19731

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000116	0.998	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.89	239	337	0.710	0.0000207	3684
Missense in Polyphen		43	90.364	0.47585		989
Synonymous	0.624	141	151	0.935	0.00000948	1247
Loss of Function	2.68	15	31.1	0.482	0.00000164	322

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000158	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000968	0.0000924
European (Non-Finnish)	0.000153	0.000149
Middle Eastern	0.000163	0.000163
South Asian	0.0000980	0.0000980
Other	0.000348	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis. Unsubstituted reduced folates are the preferred substrates. Metabolizes methotrexate (MTX) to polyglutamates. {ECO:0000269|PubMed:8408018, ECO:0000269|PubMed:8408019, ECO:0000269|PubMed:8408021, ECO:0000269|PubMed:8662720}.
• Pathway: Fluoropyrimidine Pathway, Pharmacodynamics;Folate biosynthesis - Homo sapiens (human);Methotrexate Pathway (Cancer Cell), Pharmacodynamics;Folate malabsorption, hereditary;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Methotrexate Action Pathway;Folate Metabolism;Fluoropyrimidine Activity;folate polyglutamylation;Folate metabolism;Metabolism;Metabolism of folate and pterines;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;Vitamin B9 (folate) metabolism (Consensus)

Recessive Scores

• pRec: 0.270

Intolerance Scores

• loftool: 0.742
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.7

Haploinsufficiency Scores

• pHI: 0.0868
• hipred: Y
• hipred_score: 0.515
• ghis: 0.484

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.865

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fpgs
• Phenotype: growth/size/body region phenotype

Gene ontology

• Biological process: liver development;nucleobase-containing compound metabolic process;glutamate metabolic process;one-carbon metabolic process;folic acid-containing compound metabolic process;brain development;animal organ regeneration;folic acid metabolic process;tetrahydrofolylpolyglutamate biosynthetic process
• Cellular component: cytoplasm;mitochondrion;mitochondrial inner membrane;mitochondrial matrix;cytosol
• Molecular function: tetrahydrofolylpolyglutamate synthase activity;ATP binding;metal ion binding