FPGS (folylpolyglutamate synthase)

Gene Basic Information

Gene Basic Information

symbol:
FPGS
locus group:
protein-coding gene
location:
9q34.11
gene_family:
alias symbol:
None
alias name:
None
entrez id:
2356
ensembl gene id:
ENSG00000136877
ucsc gene id:
uc004bsg.3
refseq accession:
NM_001018078
hgnc_id:
HGNC:3824
approved reserved:
2001-06-22

Chromosome Location

Chromosome Location

9q34.11

Gene Summary

Gene Summary

FPGS（folylpolyglutamate synthetase）是一种关键的代谢酶，属于叶酸代谢途径中的多聚谷氨酸合成酶家族。它的主要功能是将叶酸及其衍生物（如5,10-亚甲基四氢叶酸）转化为多聚谷氨酸形式（folylpolyglutamates），这一过程对于细胞内叶酸的保留和代谢至关重要。FPGS通过增加叶酸衍生物的谷氨酸链长度，使其带更多负电荷，从而无法轻易穿过细胞膜，确保叶酸在细胞内高效积累。此外，多聚谷氨酸化的叶酸也是多种一碳单位转移反应的必需辅因子，参与嘌呤、嘧啶合成及DNA甲基化等关键生物学过程。FPGS在增殖活跃的组织（如骨髓、肠道上皮和肿瘤）中表达较高，因为这些组织对叶酸需求旺盛。FPGS基因突变可能导致叶酸代谢障碍，引发巨幼红细胞性贫血、神经管缺陷或癌症风险增加。FPGS过表达会增强叶酸代谢通路的活性，促进核苷酸合成和细胞增殖，这在某些快速生长的肿瘤中常见，可能导致对甲氨蝶呤（一种叶酸拮抗剂类化疗药物）的耐药性。相反，FPGS表达降低会导致细胞内叶酸缺乏，影响DNA合成和修复，可能引起发育异常或造血功能障碍。FPGS属于多聚谷氨酸合成酶基因家族，该家族成员（如GGPS、DPGS等）的共同特点是能够催化谷氨酸残基与特定底物（如叶酸、泛酸）的羧基端连接，形成多聚谷氨酸链，从而调节这些分子的细胞滞留和生物活性。FPGS的活性受细胞内叶酸水平和抗氧化状态的影响，并与MTHFR、TYMS等叶酸代谢相关基因存在功能协同。在癌症治疗中，FPGS的表达水平常被作为甲氨蝶呤疗效的预测指标，因为该酶的多聚谷氨酸化作用可增强药物在细胞内的滞留和毒性。

ChineseEnglish

None

OMIM entry for FPGS     Wikipedia entry for FPGS

Gene Sequence

Gene Sequence

Nucleotide sequence of FPGS:[NCBI]
Loading Gene Browser...

Encoded Protein

Encoded Protein

Protein Sequence
1MSRARSHLRA ALFLAAASAR GITTQVAARR GLSAWPVPQE
41PSMEYQDAVR MLNTLQTNAG YLEQVKRQRG DPQTQLEAME
81 LYLARSGLQ VEDLDRLNII HVTGTKGKGS TCAFTECILR
121SYGLKTGFFS SPHLVQVRER IRINGQPISP ELFTKYFWRL
161Y HRLEETKD GSCVSMPPYF RFLTLMAFHV FLQEKVDLAV
201VEVGIGGAYD CTNIIRKPVV CGVSSLGIDH TSLLGDTVEK
241IA WQKGGIF KQGVPAFTVL QPEGPLAVLR DRAQQISCPL
281YLCPMLEALE EGGPPLTLGL EGEHQRSNAA LALQLAHCWL
321QRQ DRHGAG EPKASRPGLL WQLPLAPVFQ PTSHMRLGLR
361NTEWPGRTQV LRRGPLTWYL DGAHTASSAQ ACVRWFRQAL
401QGRE RPSGG PEVRVLLFNA TGDRDPAALL KLLQPCQFDY
441AVFCPNLTEV SSTGNADQQN FTVTLDQVLL RCLEHQQHWN
481HLDEE QASP DLWSAPSPEP GGSASLLLAP HPPHTCSASS
521LVFSCISHAL QWISQGRDPI FQPPSPPKGL LTHPVAHSGA
561SILREA AAI HVLVTGSLHL VGGVLKLLEP ALSQ
结构预测来自 AlphaFold DB（UniProt: Q05932），颜色表示 pLDDT 置信度（深蓝高、黄橙低）。

Gene Variants

Gene Variants

SNP variants of FPGS:           Showing partial SNPs
rs7018778       rs10637560       rs36121733       rs41394045       rs41485050       rs112089043       rs113327024       rs138976567       rs141440695       rs145093299       rs149054804       rs181704578       rs189421042       rs199911694       rs373487190       rs561724364       rs566595984      

Gene Expression

Gene Expression

Tissue expression of FPGS:    [UniProt]

Gene expression across tissues

Gene Primers

Gene Primers

Forward Primer
Forward Tm
Reverse Primer
Reverse Tm
Score
ATCATCAGGAAGCCTGTGG
60
CGATCTTCTCCACCGTATCC
60
CTGCCAGTTTGACTATGCC
59
TGTGAAGTTCTGTTGGTCTG
58
CTGCCAGTTTGACTATGCC
59
TGTGAAGTTCTGTTGGTCTG
58
AGACGGGATTCTTTAGCTCTC
59
AAGAGCTCAGGACTGATGG
59
ACATCATCCACGTCACTGG
60
GATACATTCCGTGAAGGCAC
59
TCTTTAAGCAAGGTGTCCC
57
TCGGACACAGGTATAGAGG
58
CTCTCCTTCTTCCCTCCAC
59
TAGAGGACATGAGATCTGCTG
59
ATCATCAGGAAGCCTGTGG
60
GATCTTCTCCACCGTATCCC
60
AACATCATCCACGTCACTG
58
ATACATTCCGTGAAGGCAC
58
TCTTTAAGCAAGGTGTCCCT
59
CGGACACAGGTATAGAGGAC
59

Transcription Factors

Transcription Factors

Transcription Factors
Target Gene
Interaction Type
PubMed References
SP1
FPGS
Unknown
20072153

Gene Ontology

Subcellular localization of FPGS (and its protein):

[UniProt]     [GenomeNet]

" d="M482.414,245.296c3.539,4.293,4.455,10.009,0.202,11 c-4.244,0.996-4.983-10.983-8.293-8.438c-5.271,4.08,9.834,12.271,5.144,17.287c-3.717,3.607-6.172-5.75-10.839-1.976 c-4.673,3.776,6.781,7.299,2.831,11.326c-4.354,4.045-6.979-1.449-9.837-5.517c-1.193-1.742-2.059-3.851-3.595-2.748 c-1.516,1.078-1.854,1.795-0.938,3.666c2.374,4.854,9.235,10.119,5.156,12.535c-5.636,3.346-5.044-8.871-9.426-7.574 c-4.388,1.291,2.557,10.66-1.245,11.141c-4.089,0.545-3.483-10.239-6.979-8.575c-2.522,1.206-0.929,3.071-0.938,4.899 c0.004,1.32-0.964,3.6-2.372,4.062c-3.593,1.171-8.544-1.065-10.251-3.59c-6.04-8.93,0.396-15.997,4.639-7.015 c3.023,4.642,5.182,0.834,2.839-2.219c-1.032-1.354-4.309-5.901-0.781-7.252c2.904-1.113,4.271,1.941,5.985,4.592 c2.61,4.016,5.485,0.117,3.031-3.414c-1.828-2.633-2.74-3.803,3.156-7.42c6.405-4.369,6.52,3.869,10.077,0.646 c2.309-1.832-4.783-5.149,0.06-8.995c2.896-2.293,5.18,6.207,7.961,3.516c3.523-2.737-7.717-7.369,0.117-11.736 C473.413,240.77,480.519,242.891,482.414,245.296z"/> Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
  • plasma membrane
  • cytoplasm
  • extracellular
  • golgi
  • vesicle
  • cytoskeleton
  • endoplasmic reticulum
  • nucleus
  • endosome
  • lysosome
  • mitochondrion

Gene Ontology (GO) terms for FPGS:

GO ID
Protein
Source DB
GO:0001889
Q05932 (UniProtKB)
IEA
GO:0004326
Q05932 (UniProtKB)
IDA
GO:0004326
Q05932 (UniProtKB)
IDA
GO:0004326
Q05932 (UniProtKB)
IDA
GO:0004326
Q05932 (UniProtKB)
TAS
GO:0004326
Q05932 (UniProtKB)
TAS
GO:0004326
Q05932 (UniProtKB)
TAS
GO:0005524
Q05932 (UniProtKB)
IEA
GO:0005737
Q05932 (UniProtKB)
TAS
GO:0005739
Q05932 (UniProtKB)
IDA
GO:0005739
Q05932 (UniProtKB)
TAS
GO:0005743
Q05932 (UniProtKB)
IEA
GO:0005759
Q05932 (UniProtKB)
TAS
GO:0005829
Q05932 (UniProtKB)
IDA
GO:0005829
Q05932 (UniProtKB)
TAS
GO:0005829
Q05932 (UniProtKB)
TAS
GO:0006139
Q05932 (UniProtKB)
TAS
GO:0006536
Q05932 (UniProtKB)
IDA
GO:0006730
Q05932 (UniProtKB)
IEA
GO:0006760
Q05932 (UniProtKB)
IDA
GO:0007420
Q05932 (UniProtKB)
IEA
GO:0008283
Q05932 (UniProtKB)
IMP
GO:0008283
Q05932 (UniProtKB)
IMP
GO:0031100
Q05932 (UniProtKB)
IEA
GO:0046655
Q05932 (UniProtKB)
TAS
GO:0046901
Q05932 (UniProtKB)
IEA
GO:0046901
Q05932 (UniProtKB)
IDA
GO:0046901
Q05932 (UniProtKB)
IDA
GO:0046901
Q05932 (UniProtKB)
IDA
GO:0004326
Q5JU20 (UniProtKB)
IEA
GO:0005524
Q5JU20 (UniProtKB)
IEA
GO:0046901
Q5JU20 (UniProtKB)
IEA
GO:0004326
Q5JU21 (UniProtKB)
IEA
GO:0005524
Q5JU21 (UniProtKB)
IEA
GO:0046901
Q5JU21 (UniProtKB)
IEA
GO:0004326
Q5JU23 (UniProtKB)
IEA
GO:0005524
Q5JU23 (UniProtKB)
IEA
GO:0046901
Q5JU23 (UniProtKB)
IEA

Related microRNA

Related microRNA

microRNAs potentially regulating FPGS:     

Gene Interactions

Gene Interactions

String
BioGrid
mentha
Reactome
Loading…
Interacting Gene Interaction Source/Score

Gene Pathways

Gene Pathways

Related Diseases

Related Diseases

Disease Score NofPmids NofSnps Source
Disease Score NofPmids NofSnps Source
Rheumatoid Arthritis 0.127101096 4 0 CTD_human_GAD
Lymphoma, Non-Hodgkin 0.124734064 2 0 CTD_human_GAD
Colorectal Neoplasms 0.12272435 2 0 CTD_human_LHGDN
Malignant neoplasm of lung 0.004734064 2 0 GAD
B-Cell Lymphomas 0.002367032 1 0 GAD
Drug-Induced Liver Injury 0.002367032 1 0 GAD
Gastrointestinal Diseases 0.002367032 1 0 GAD
Spina Bifida 0.002367032 1 0 GAD
Psoriasis 0.002367032 1 0 GAD
Diffuse Large B-Cell Lymphoma 0.002367032 1 0 GAD

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