GPI glucose-6-phosphate isomerase [Homo sapiens (human)] - Gene

Summary

Official Symbol: GPIprovided by HGNC
Official Full Name: glucose-6-phosphate isomeraseprovided by HGNC
Primary source: HGNC:HGNC:4458
See related: Ensembl:ENSG00000105220 MIM:172400; AllianceGenome:HGNC:4458
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
Also known as: AMF; NLK; PGI; PHI; GNPI; SA36; SA-36
Summary: This gene encodes a member of the glucose phosphate isomerase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In the cytoplasm, the gene product functions as a glycolytic enzyme (glucose-6-phosphate isomerase) that interconverts glucose-6-phosphate and fructose-6-phosphate. Extracellularly, the encoded protein (also referred to as neuroleukin) functions as a neurotrophic factor that promotes survival of skeletal motor neurons and sensory neurons, and as a lymphokine that induces immunoglobulin secretion. The encoded protein is also referred to as autocrine motility factor based on an additional function as a tumor-secreted cytokine and angiogenic factor. Defects in this gene are the cause of nonspherocytic hemolytic anemia and a severe enzyme deficiency can be associated with hydrops fetalis, immediate neonatal death and neurological impairment. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]
Expression: Ubiquitous expression in heart (RPKM 54.9), fat (RPKM 52.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.11

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (34359718..34402413)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (36886877..36946977)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (34855645..34893318)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Clinical, laboratory, and mutational profile of children with glucose phosphate isomerase deficiency: a single centre report.
Title: Clinical, laboratory, and mutational profile of children with glucose phosphate isomerase deficiency: a single centre report.
Elevated Serum Glucose-6-Phosphate Isomerase Level in Patients with Knee Osteoarthritis.
Title: Elevated Serum Glucose-6-Phosphate Isomerase Level in Patients with Knee Osteoarthritis.
Whole-transcriptome Analysis of Fully Viable Energy Efficient Glycolytic-null Cancer Cells Established by Double Genetic Knockout of Lactate Dehydrogenase A/B or Glucose-6-Phosphate Isomerase.
Title: Whole-transcriptome Analysis of Fully Viable Energy Efficient Glycolytic-null Cancer Cells Established by Double Genetic Knockout of Lactate Dehydrogenase A/B or Glucose-6-Phosphate Isomerase.
Secreted phosphoglucose isomerase is a novel biomarker of nonalcoholic fatty liver in mice and humans.
Title: Secreted phosphoglucose isomerase is a novel biomarker of nonalcoholic fatty liver in mice and humans.
Autocrine motility factor secreted by HeLa cells inhibits the growth of many cancer cells by regulating AKT/ERK signaling.
Title: Autocrine motility factor secreted by HeLa cells inhibits the growth of many cancer cells by regulating AKT/ERK signaling.
Proteomics analysis of asthenozoospermia and identification of glucose-6-phosphate isomerase as an important enzyme for sperm motility.
Title: Proteomics analysis of asthenozoospermia and identification of glucose-6-phosphate isomerase as an important enzyme for sperm motility.
This report describes the high prevalence of p.Arg347His pathogenic variant identified in Indian GPI deficient patients with hemolytic anemia and neuromuscular impairment.
Title: Glucose Phosphate Isomerase Deficiency: High Prevalence of p.Arg347His Mutation in Indian Population Associated with Severe Hereditary Non-Spherocytic Hemolytic Anemia Coupled with Neurological Dysfunction.
High GPI expression is associated with glioblastoma cell migration and invasion.
Title: The secreted glycolytic enzyme GPI/AMF stimulates glioblastoma cell migration and invasion in an autocrine fashion but can have anti-proliferative effects.
we describe new p.(Arg472Cys) and p.(Ser160Pro) GPI mutations in the first cases of GPI deficiency in the Czech and Slovak populations.
Title: Two novel mutations (p.(Ser160Pro) and p.(Arg472Cys)) causing glucose-6-phosphate isomerase deficiency are associated with erythroid dysplasia and inappropriately suppressed hepcidin.
Study demonstrated a novel pathway regulating hypoxia-induced angiogenesis in rheumatoid arthritis mediated by glucose-6-phosphate isomerase.
Title: Glucose-6-Phosphate Isomerase (G6PI) Mediates Hypoxia-Induced Angiogenesis in Rheumatoid Arthritis.

Submit: New GeneRIF Correction See all GeneRIFs (59)

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

Associated conditions

Description	Tests
Hemolytic anemia due to glucophosphate isomerase deficiency MedGen: C3150730 OMIM: 613470 GeneReviews: Not available	Compare labs

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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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Glucophosphoisomerase (GPI) can be antagonized by the human immunodeficiency virus (HIV-1) gp120 protein in human and rat neuroblastoma cell lines	PubMed
Tat	tat	Expression of HIV-1 Tat upregulates the abundance of glucose-6-phosphate isomerase (GPI) in the nucleoli of Jurkat T-cells	PubMed
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of glucose-6-phosphate isomerase (GPI) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

GDB:434012 (e-PCR)
- UniSTS:157204

D19S630E (e-PCR)
- UniSTS:150553

D11S2560 (e-PCR)
- UniSTS:37928

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

SHGC-111277 (e-PCR)
- UniSTS:168272

L18426 (e-PCR)
- UniSTS:34648

GPI (e-PCR), detects polymorphism
- UniSTS:504411

D22S1584 (e-PCR)
- UniSTS:473695

IB853 (e-PCR)
- UniSTS:44642

D10S16 (e-PCR)
- UniSTS:155756

D1S1423 (e-PCR)
- UniSTS:149619

D1S1425 (e-PCR)
- UniSTS:149621

G35510 (e-PCR)
- UniSTS:44150

PMC164521P1 (e-PCR)
- UniSTS:271494

D11S3114 (e-PCR)
- UniSTS:152207

D19S984 (e-PCR)
- UniSTS:48055

NoName (e-PCR)
- UniSTS:47058

STS-K03515 (e-PCR)
- UniSTS:46079

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables carbohydrate derivative binding	IEA Inferred from Electronic Annotation more info
enables cytokine activity	IEA Inferred from Electronic Annotation more info
enables glucose-6-phosphate isomerase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glucose-6-phosphate isomerase activity	IDA Inferred from Direct Assay more info	PubMed
enables growth factor activity	IEA Inferred from Electronic Annotation more info
enables monosaccharide binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in carbohydrate metabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in erythrocyte homeostasis	IEA Inferred from Electronic Annotation more info
involved_in gluconeogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in glucose 6-phosphate metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glucose 6-phosphate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in glucose homeostasis	IEA Inferred from Electronic Annotation more info
involved_in glycolytic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glycolytic process	IEA Inferred from Electronic Annotation more info
involved_in hemostasis	TAS Traceable Author Statement more info	PubMed
involved_in humoral immune response	TAS Traceable Author Statement more info	PubMed
involved_in in utero embryonic development	IEA Inferred from Electronic Annotation more info
involved_in learning or memory	IEA Inferred from Electronic Annotation more info
involved_in mesoderm formation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of immunoglobulin production	IDA Inferred from Direct Assay more info	PubMed
involved_in response to cadmium ion	IEA Inferred from Electronic Annotation more info
involved_in response to estradiol	IEA Inferred from Electronic Annotation more info
involved_in response to immobilization stress	IEA Inferred from Electronic Annotation more info
involved_in response to muscle stretch	IEA Inferred from Electronic Annotation more info
involved_in response to progesterone	IEA Inferred from Electronic Annotation more info
involved_in response to testosterone	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in ciliary membrane	IEA Inferred from Electronic Annotation more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in ficolin-1-rich granule lumen	TAS Traceable Author Statement more info
located_in membrane	HDA more info	PubMed
located_in secretory granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: glucose-6-phosphate isomerase

Names: autocrine motility factor; hexose monophosphate isomerase; hexosephosphate isomerase; neuroleukin; oxoisomerase; phosphoglucose isomerase; phosphohexomutase; phosphohexose isomerase; phosphosaccharomutase; sperm antigen-36

NP_000166.2

EC 5.3.1.9

NP_001171651.1

EC 5.3.1.9

NP_001276718.1

EC 5.3.1.9

NP_001276719.1

EC 5.3.1.9

NP_001316838.1

EC 5.3.1.9

NP_001316839.1

EC 5.3.1.9

NP_001316840.1

EC 5.3.1.9

XP_011525056.1

EC 5.3.1.9

XP_054176557.1

EC 5.3.1.9

XP_054189232.1

EC 5.3.1.9

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_012838.3 RefSeqGene

Range

10605..47822

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1178

mRNA and Protein(s)

NM_000175.5 → NP_000166.2 glucose-6-phosphate isomerase isoform 2

See identical proteins and their annotated locations for NP_000166.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and uses a downstream start codon, compared to variant 3. The encoded isoform (2) has a shorter N-terminus, compared to isoform 3.

Source sequence(s)

AC092073, BC004982, BM664761, DC299841

Consensus CDS

CCDS12437.1

UniProtKB/Swiss-Prot

B4DG39, P06744, Q9BRD3, Q9BSK5, Q9UHE6

UniProtKB/TrEMBL

A0A1W6AYU6

Related

ENSP00000348877.3, ENST00000356487.11

Conserved Domains (1) summary

PRK00179
Location:1 → 554

pgi; glucose-6-phosphate isomerase; Reviewed
NM_001184722.1 → NP_001171651.1 glucose-6-phosphate isomerase isoform 1

See identical proteins and their annotated locations for NP_001171651.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) lacks an in-frame exon in the central coding region, compared to variant 3. The encoded isoform (1) is shorter, compared to isoform 3.

Source sequence(s)

AC010504, AC092073, AK294396, BM664761, DC342043

Consensus CDS

CCDS54246.1

UniProtKB/TrEMBL

A0A1W6AYU6

Related

ENSP00000465858.3, ENST00000588991.7

Conserved Domains (3) summary

PRK00179
Location:40 → 565

pgi; glucose-6-phosphate isomerase; Reviewed

cd05015
Location:162 → 297

SIS_PGI_1; Phosphoglucose isomerase (PGI) contains two SIS (Sugar ISomerase) domains. This classification is based on the alignment of the first SIS domain. PGI is a multifunctional enzyme which as an intracellular dimer catalyzes the reversible isomerization of ...

cd05016
Location:345 → 536

SIS_PGI_2; Phosphoglucose isomerase (PGI) contains two SIS (Sugar ISomerase) domains. This classification is based on the alignment of the second SIS domain. PGI is a multifunctional enzyme which as an intracellular dimer catalyzes the reversible isomerization of ...
NM_001289789.1 → NP_001276718.1 glucose-6-phosphate isomerase isoform 3

See identical proteins and their annotated locations for NP_001276718.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (3).

Source sequence(s)

AK129884, BC006342, CR745343, DC342043, FY213211

Consensus CDS

CCDS86742.1

UniProtKB/TrEMBL

A0A1W6AYU6, A0A2U3TZU2

Related

ENSP00000405573.3, ENST00000415930.8

Conserved Domains (3) summary

PRK00179
Location:40 → 593

pgi; glucose-6-phosphate isomerase; Reviewed

cd05015
Location:162 → 325

SIS_PGI_1; Phosphoglucose isomerase (PGI) contains two SIS (Sugar ISomerase) domains. This classification is based on the alignment of the first SIS domain. PGI is a multifunctional enzyme which as an intracellular dimer catalyzes the reversible isomerization of ...

cd05016
Location:373 → 564

SIS_PGI_2; Phosphoglucose isomerase (PGI) contains two SIS (Sugar ISomerase) domains. This classification is based on the alignment of the second SIS domain. PGI is a multifunctional enzyme which as an intracellular dimer catalyzes the reversible isomerization of ...
NM_001289790.3 → NP_001276719.1 glucose-6-phosphate isomerase isoform 4

See identical proteins and their annotated locations for NP_001276719.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR, uses a downstream start codon, and lacks an in-frame exon in the central coding region, compared to variant 3. The encoded isoform (4) is shorter, compared to isoform 3.

Source sequence(s)

AK293446, BC006342, CR745343, DC299841, FY213211

UniProtKB/TrEMBL

A0A1W6AYU6, B4DE36

Conserved Domains (3) summary

PRK00179
Location:1 → 526

pgi; glucose-6-phosphate isomerase; Reviewed

cd05015
Location:123 → 258

SIS_PGI_1; Phosphoglucose isomerase (PGI) contains two SIS (Sugar ISomerase) domains. This classification is based on the alignment of the first SIS domain. PGI is a multifunctional enzyme which as an intracellular dimer catalyzes the reversible isomerization of ...

cd05016
Location:306 → 497

SIS_PGI_2; Phosphoglucose isomerase (PGI) contains two SIS (Sugar ISomerase) domains. This classification is based on the alignment of the second SIS domain. PGI is a multifunctional enzyme which as an intracellular dimer catalyzes the reversible isomerization of ...
NM_001329909.1 → NP_001316838.1 glucose-6-phosphate isomerase isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and uses a downstream start codon, compared to variant 3. The encoded isoform (2) is shorter, compared to isoform 3.

Source sequence(s)

AK129884, BC004982, BC006342, BM664761, DA158837, DA171856

Consensus CDS

CCDS12437.1

UniProtKB/Swiss-Prot

B4DG39, P06744, Q9BRD3, Q9BSK5, Q9UHE6

UniProtKB/TrEMBL

A0A1W6AYU6

Conserved Domains (1) summary

PRK00179
Location:1 → 554

pgi; glucose-6-phosphate isomerase; Reviewed
NM_001329910.1 → NP_001316839.1 glucose-6-phosphate isomerase isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 5' UTR and uses a downstream start codon, compared to variant 3. The encoded isoform (2) is shorter, compared to isoform 3.

Source sequence(s)

BC004982, BC006342, BM664761, DA158837, DA171856, DA909998

Consensus CDS

CCDS12437.1

UniProtKB/Swiss-Prot

B4DG39, P06744, Q9BRD3, Q9BSK5, Q9UHE6

UniProtKB/TrEMBL

A0A1W6AYU6

Conserved Domains (1) summary

PRK00179
Location:1 → 554

pgi; glucose-6-phosphate isomerase; Reviewed
NM_001329911.2 → NP_001316840.1 glucose-6-phosphate isomerase isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (7) differs in the 5' UTR, uses a downstream start codon, and uses an alternate in-frame splice site in the 3' coding region, compared to variant 3. The encoded isoform (5) is shorter, compared to isoform 3.

Source sequence(s)

AC092073, BC004982, BM664761, DC299841, HY310615

UniProtKB/TrEMBL

A0A1W6AYU6

Related

ENSP00000467670.3, ENST00000586425.2

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

34359718..34402413

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011526754.4 → XP_011525056.1 glucose-6-phosphate isomerase isoform X1

See identical proteins and their annotated locations for XP_011525056.1

UniProtKB/TrEMBL

A0A1W6AYU6, A0A2U3TZU2

Conserved Domains (3) summary

PRK00179
Location:40 → 593

pgi; glucose-6-phosphate isomerase; Reviewed

cd05015
Location:162 → 325

SIS_PGI_1; Phosphoglucose isomerase (PGI) contains two SIS (Sugar ISomerase) domains. This classification is based on the alignment of the first SIS domain. PGI is a multifunctional enzyme which as an intracellular dimer catalyzes the reversible isomerization of ...

cd05016
Location:373 → 564

SIS_PGI_2; Phosphoglucose isomerase (PGI) contains two SIS (Sugar ISomerase) domains. This classification is based on the alignment of the second SIS domain. PGI is a multifunctional enzyme which as an intracellular dimer catalyzes the reversible isomerization of ...