FPGS folylpolyglutamate synthase [Homo sapiens (human)] - Gene

Summary

Official Symbol: FPGSprovided by HGNC
Official Full Name: folylpolyglutamate synthaseprovided by HGNC
Primary source: HGNC:HGNC:3824
See related: Ensembl:ENSG00000136877 MIM:136510; AllianceGenome:HGNC:3824
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: This gene encodes the folylpolyglutamate synthetase enzyme. This enzyme has a central role in establishing and maintaining both cytosolic and mitochondrial folylpolyglutamate concentrations and, therefore, is essential for folate homeostasis and the survival of proliferating cells. This enzyme catalyzes the ATP-dependent addition of glutamate moieties to folate and folate derivatives. Alternative splicing results in transcript variants encoding different isoforms. [provided by RefSeq, Jan 2014]
Expression: Ubiquitous expression in ovary (RPKM 14.6), fat (RPKM 12.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9q34.11

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (127802858..127814506)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (140010277..140025149)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (130565137..130576360)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Effects of single nucleotide polymorphisms of the folylpolyglutamate synthase gene on pemetrexed administration-induced nephropathy.
Title: Effects of single nucleotide polymorphisms of the folylpolyglutamate synthase gene on pemetrexed administration-induced nephropathy.
Influence of FPGS, ABCC4, SLC29A1, and MTHFR genes on the pharmacogenomics of fluoropyrimidines in patients with gastrointestinal cancer from the Brazilian Amazon.
Title: Influence of FPGS, ABCC4, SLC29A1, and MTHFR genes on the pharmacogenomics of fluoropyrimidines in patients with gastrointestinal cancer from the Brazilian Amazon.
Association of altered folylpolyglutamate synthetase pre-mRNA splicing with methotrexate unresponsiveness in early rheumatoid arthritis.
Title: Association of altered folylpolyglutamate synthetase pre-mRNA splicing with methotrexate unresponsiveness in early rheumatoid arthritis.
Effects of germline DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia.
Title: Effects of germline DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia.
Association of NUDT15*3 and FPGS 2572C>T Variants with the Risk of Early Hematologic Toxicity During 6-MP and Low-Dose Methotrexate-Based Maintenance Therapy in Indian Patients with Acute Lymphoblastic Leukemia.
Title: Association of NUDT15*3 and FPGS 2572C>T Variants with the Risk of Early Hematologic Toxicity During 6-MP and Low-Dose Methotrexate-Based Maintenance Therapy in Indian Patients with Acute Lymphoblastic Leukemia.
FPGS relapse-specific mutations in relapsed childhood acute lymphoblastic leukemia.
Title: FPGS relapse-specific mutations in relapsed childhood acute lymphoblastic leukemia.
our study has established the de novo MTX-resistant cell line SF-86 and identified SKA1 as a novel regulator of FPGS, playing a key role in the development of de novo MTX-resistance in osteosarcoma (OS).
Title: SKA1 induces de novo MTX-resistance in osteosarcoma through inhibiting FPGS transcription.
analysis of seven polymorphisms in genes of folate transport and (de)glutamation pathway on methotrexate polyglutamate levels and response in patients with rheumatoid arthritis: ABCB1, FPGS, GGH and RFC1
Title: Do SNPs in folate pharmacokinetic pathway alter levels of intracellular methotrexate polyglutamates and affect response? A prospective study in Indian patients.
The association of aberrant folylpolyglutamate synthetase splicing with ex vivo methotrexate resistance and clinical outcome in childhood acute lymphoblastic leukemia.
Title: The association of aberrant folylpolyglutamate synthetase splicing with ex vivo methotrexate resistance and clinical outcome in childhood acute lymphoblastic leukemia.
Low expression level of FPGS is associated with neuroendocrine lung tumors.
Title: Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome.

Submit: New GeneRIF Correction See all GeneRIFs (45)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of folylpolyglutamate synthase (FPGS) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-U40863 (e-PCR)
- UniSTS:51516

STS-M98045 (e-PCR)
- UniSTS:14221

D9S2052 (e-PCR)
- UniSTS:7566

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables tetrahydrofolylpolyglutamate synthase activity	IBA Inferred from Biological aspect of Ancestor more info
enables tetrahydrofolylpolyglutamate synthase activity	IDA Inferred from Direct Assay more info	PubMed
enables tetrahydrofolylpolyglutamate synthase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in animal organ regeneration	IEA Inferred from Electronic Annotation more info
involved_in cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in folic acid metabolic process	TAS Traceable Author Statement more info
involved_in folic acid-containing compound metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in glutamate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in liver development	IEA Inferred from Electronic Annotation more info
involved_in nucleobase-containing compound metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in one-carbon metabolic process	IEA Inferred from Electronic Annotation more info
involved_in tetrahydrofolylpolyglutamate biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in tetrahydrofolylpolyglutamate biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in tetrahydrofolylpolyglutamate biosynthetic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in mitochondrial inner membrane	IEA Inferred from Electronic Annotation more info
is_active_in mitochondrial matrix	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: folylpolyglutamate synthase, mitochondrial

Names: folylpoly-gamma-glutamate synthetase; tetrahydrofolate synthase; tetrahydrofolylpolyglutamate synthase

NP_001018088.1

EC 6.3.2.17

NP_001275732.1

EC 6.3.2.17

NP_004948.4

EC 6.3.2.17

XP_005251921.1

EC 6.3.2.17

XP_047279082.1

EC 6.3.2.17

XP_047279083.1

EC 6.3.2.17

XP_054218546.1

EC 6.3.2.17

XP_054218547.1

EC 6.3.2.17

XP_054218548.1

EC 6.3.2.17

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_023245.1 RefSeqGene

Range

5008..16207

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001018078.2 → NP_001018088.1 folylpolyglutamate synthase, mitochondrial isoform b

See identical proteins and their annotated locations for NP_001018088.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate exon for its 5' UTR and uses a downstream start codon, compared to variant 1. It encodes isoform b which is a cytosolic protein and has a shorter N-terminus, compared to isoform a.

Source sequence(s)

AK056920, CB854085, DA987755

Consensus CDS

CCDS35149.1

UniProtKB/Swiss-Prot

Q05932

Related

ENSP00000362322.3, ENST00000373225.7

Conserved Domains (2) summary

PLN02881
Location:16 → 531

PLN02881; tetrahydrofolylpolyglutamate synthase

pfam02875
Location:310 → 391

Mur_ligase_C; Mur ligase family, glutamate ligase domain
NM_001288803.1 → NP_001275732.1 folylpolyglutamate synthase, mitochondrial isoform c precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. This variant has two alternative translational start codons in the same reading frame which encode either a longer, signal-containing mitochondrial protein (isoform c) or a shorter, signal-less cytosolic protein.

Source sequence(s)

AK295309, CB854085, DC365273

Consensus CDS

CCDS75905.1

UniProtKB/Swiss-Prot

Q05932

Related

ENSP00000377309.2, ENST00000393706.6

Conserved Domains (2) summary

PLN02881
Location:42 → 555

PLN02881; tetrahydrofolylpolyglutamate synthase

pfam02875
Location:334 → 415

Mur_ligase_C; Mur ligase family, glutamate ligase domain
NM_004957.6 → NP_004948.4 folylpolyglutamate synthase, mitochondrial isoform a precursor

See identical proteins and their annotated locations for NP_004948.4

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes isoform (a). This variant has two alternative translational start codons in the same reading frame which encode either a longer, signal-containing mitochondrial protein or a shorter, signal-less cytosolic protein.

Source sequence(s)

BC007121, BC064393, CB854085, DC365273

Consensus CDS

CCDS35148.1

UniProtKB/Swiss-Prot

B3KPW4, B7Z2Z3, F5H0K6, Q05932, Q5JU19, Q5JU22, Q6P2P6

Related

ENSP00000362344.2, ENST00000373247.7

Conserved Domains (2) summary

PLN02881
Location:42 → 581

PLN02881; tetrahydrofolylpolyglutamate synthase

pfam02875
Location:360 → 441

Mur_ligase_C; Mur ligase family, glutamate ligase domain

RNA

NR_110170.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate splice site, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC009901, BG328181, CB854085, DC365273

Related

ENST00000460181.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

127802858..127814506

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005251864.5 → XP_005251921.1 folylpolyglutamate synthase, mitochondrial isoform X2

Conserved Domains (2) summary

PLN02881
Location:42 → 441

PLN02881; tetrahydrofolylpolyglutamate synthase

pfam02875
Location:360 → 441

Mur_ligase_C; Mur ligase family, glutamate ligase domain
XM_047423127.1 → XP_047279083.1 folylpolyglutamate synthase, mitochondrial isoform X3
XM_047423126.1 → XP_047279082.1 folylpolyglutamate synthase, mitochondrial isoform X1

Alternate T2T-CHM13v2.0

Genomic

NC_060933.1 Alternate T2T-CHM13v2.0

Range

140010277..140025149

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054362572.1 → XP_054218547.1 folylpolyglutamate synthase, mitochondrial isoform X2
XM_054362573.1 → XP_054218548.1 folylpolyglutamate synthase, mitochondrial isoform X3
XM_054362571.1 → XP_054218546.1 folylpolyglutamate synthase, mitochondrial isoform X1