PDX1 pancreatic and duodenal homeobox 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PDX1provided by HGNC
Official Full Name: pancreatic and duodenal homeobox 1provided by HGNC
Primary source: HGNC:HGNC:6107
See related: Ensembl:ENSG00000139515 MIM:600733; Vega:OTTHUMG00000016638
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: GSF; IPF1; IUF1; IDX-1; MODY4; PDX-1; STF-1; PAGEN1
Summary: The protein encoded by this gene is a transcriptional activator of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide, and glucose transporter type 2. The encoded nuclear protein is involved in the early development of the pancreas and plays a major role in glucose-dependent regulation of insulin gene expression. Defects in this gene are a cause of pancreatic agenesis, which can lead to early-onset insulin-dependent diabetes mellitus (IDDM), as well as maturity onset diabetes of the young type 4 (MODY4). [provided by RefSeq, Aug 2017]
Orthologs: mouse all

Genomic context

See PDX1 in Genome Data Viewer Map Viewer

Location:: 13q12.2

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
108	current	GRCh38.p7 (GCF_000001405.33)	13	NC_000013.11 (27919982..27926314)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	13	NC_000013.10 (28494168..28500451)

Chromosome 13 - NC_000013.11 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 Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Mutation in PDX1 gene is associated with Maturity Onset Diabetes of the Young.
Title: Comprehensive Maturity Onset Diabetes of the Young (MODY) Gene Screening in Pregnant Women with Diabetes in India.
Results found that Pdx-1 overexpression exerts its effects on islet cell replication via a noncell-autonomous mechanism involving induction of a secreted soluble factor or factors. Also, Inhbb is identified as one factor mediating the proliferative effect of Pdx-1.
Title: A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation.
Our findings indicate that MET induces the differentiation of Pdx1-expressing cells within the definitive endoderm in a time-dependent manner, and suggest useful application for regenerative medicine.
Title: Mild electrical stimulation with heat shock guides differentiation of embryonic stem cells into Pdx1-expressing cells within the definitive endoderm.
Pdx1 and MafA play crucial roles in the pancreas and maintain mature beta-cell function. Our results showed that the expression of Pdx1 and MafA were significantly upregulated after a sleeve gastrectomy for morbid obesity.
Title: Upregulated Pdx1 and MafA Contribute to β-Cell Function Improvement by Sleeve Gastrectomy.
Data show that the expression patterns of sex determining region Y-box 2 (SOX2) and pancreatic and duodenal homeobox 1 (Pdx1)) highly correlated with prognosis of pancreatic neuroendocrine tumors (p-NETs).
Title: Expression of Sex Determining Region Y-Box 2 and Pancreatic and Duodenal Homeobox 1 in Pancreatic Neuroendocrine Tumors.
The ERK-PDX-1 interaction in PANC-1 cells.
Title: Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma.
Foxo1 and PDX1 are colocalized in fetal pancreatic islets, suggesting they function in parallel in beta cells.
Title: FoxO1 Plays an Important Role in Regulating β-Cell Compensation for Insulin Resistance in Male Mice.
This study investigated the role of Pdx1 and its mechanism in differentiating induced pluripotent stem cells (iPSCs) into islet beta cells.
Title: Pdxl and its role in activating Ngn3 and Pax6 to induce differentiation of iPSCs into islet β cells.
the human Pdx1 is highly effective in triggering human biliary tree stem cells differentiation toward functional beta-pancreatic cells.
Title: Adult Human Biliary Tree Stem Cells Differentiate to β-Pancreatic Islet Cells by Treatment with a Recombinant Human Pdx1 Peptide.
Introduction of the PDX1 gene makes cells acquire a functional insulin secretory capacity
Title: Forced expression of PDX-1 gene makes hepatoma cells to acquire glucose-responsive insulin secretion while maintaining hepatic characteristic.

Submit: New GeneRIF Correction See all GeneRIFs (112)

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
Diabetes mellitus type 2 MedGen: C0011860 OMIM: 125853 GeneReviews: Not available	Compare labs
Maturity-onset diabetes of the young, type 4 MedGen: C1833382 OMIM: 606392 GeneReviews: Not available	Compare labs
Pancreatic agenesis, congenital MedGen: C1850096 OMIM: 260370 GeneReviews: Not available	Compare labs
Permanent neonatal diabetes mellitus MedGen: C1833104 OMIM: 606176 GeneReviews: Permanent Neonatal Diabetes Mellitus	Compare labs

NHGRI GWAS Catalog

Description
A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Conduct disorder and ADHD: evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Developmental Biology, organism-specific biosystem (from REACTOME)
Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
FOXA2 and FOXA3 transcription factor networks, organism-specific biosystem (from Pathway Interaction Database)
FOXA2 and FOXA3 transcription factor networks, organism-specific biosystem
FOXA2 and FOXA3 transcription factor networks
Insulin secretion, organism-specific biosystem (from KEGG)
Insulin secretion, organism-specific biosystemPancreatic beta cells are specialised endocrine cells that continuously sense the levels of blood sugar and other fuels and, in response, secrete insulin to maintain normal fuel homeostasis. Glucose-...
Maturity onset diabetes of the young, organism-specific biosystem (from KEGG)
Maturity onset diabetes of the young, organism-specific biosystemAbout 2-5% of type II diabetic patients suffer from a monogenic disease with autosomal dominant inheritance. This monogenic form of type II diabetes is called maturity onset diabetes of the young (MO...
Maturity onset diabetes of the young, conserved biosystem (from KEGG)
Maturity onset diabetes of the young, conserved biosystemAbout 2-5% of type II diabetic patients suffer from a monogenic disease with autosomal dominant inheritance. This monogenic form of type II diabetes is called maturity onset diabetes of the young (MO...
Regulation of beta-cell development, organism-specific biosystem (from REACTOME)
Regulation of beta-cell development, organism-specific biosystemThe normal development of the pancreas during gestation has been intensively investigated over the past decade especially in the mouse (Servitja and Ferrer 2004; Chakrabarti and Mirmira 2003). Studie...
Regulation of gene expression in beta cells, organism-specific biosystem (from REACTOME)
Regulation of gene expression in beta cells, organism-specific biosystemTwo transcription factors, PDX1 and HNF1A, play key roles in maintaining the gene expression pattern characteristic of mature beta cells in the endocrine pancreas. Targets of these regulatory molecul...
Regulation of gene expression in early pancreatic precursor cells, organism-specific biosystem (from REACTOME)
Regulation of gene expression in early pancreatic precursor cells, organism-specific biosystemThe properties of transcriptional networks early in the differentiation of human pancreatic cells are inferred from the properties of well-studied networks in mouse models. In mice, the first visible...
Type II diabetes mellitus, organism-specific biosystem (from KEGG)
Type II diabetes mellitus, organism-specific biosystemInsulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Ser...
Type II diabetes mellitus, conserved biosystem (from KEGG)
Type II diabetes mellitus, conserved biosystemInsulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Ser...
Type II diabetes mellitus, organism-specific biosystem (from WikiPathways)
Type II diabetes mellitus, organism-specific biosystemInsulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Ser...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G05158 (e-PCR)
- UniSTS:3169

Pdx1 (e-PCR), detects polymorphism
- UniSTS:464793

Pdx1 (e-PCR), detects polymorphism
- UniSTS:224153

NoName (e-PCR)
- UniSTS:483240

RH79140 (e-PCR)
- UniSTS:37111

Homology

Homologs of the PDX1 gene: The PDX1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 190 organisms have orthologs with human gene PDX1
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
RNA polymerase II core promoter proximal region sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
chromatin binding	IEA Inferred from Electronic Annotation more info
core promoter sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
protein complex binding	IEA Inferred from Electronic Annotation more info
protein heterodimerization activity	IEA Inferred from Electronic Annotation more info
transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding	IEA Inferred from Electronic Annotation more info
transcription factor activity, sequence-specific DNA binding	TAS Traceable Author Statement more info	PubMed
transcription factor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
animal organ morphogenesis	TAS Traceable Author Statement more info	PubMed
animal organ regeneration	IEA Inferred from Electronic Annotation more info
animal organ senescence	IEA Inferred from Electronic Annotation more info
central nervous system development	IEA Inferred from Electronic Annotation more info
detection of glucose	ISS Inferred from Sequence or Structural Similarity more info
digestive tract development	IEA Inferred from Electronic Annotation more info
exocrine pancreas development	IEA Inferred from Electronic Annotation more info
generation of precursor metabolites and energy	TAS Traceable Author Statement more info	PubMed
glucose homeostasis	IEA Inferred from Electronic Annotation more info
glucose metabolic process	IEA Inferred from Electronic Annotation more info
insulin secretion	IDA Inferred from Direct Assay more info	PubMed
liver development	IEA Inferred from Electronic Annotation more info
morphogenesis of embryonic epithelium	IEA Inferred from Electronic Annotation more info
negative regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of transcription from RNA polymerase II promoter	IEA Inferred from Electronic Annotation more info
negative regulation of type B pancreatic cell apoptotic process	IEA Inferred from Electronic Annotation more info
nitric oxide mediated signal transduction	IDA Inferred from Direct Assay more info	PubMed
positive regulation of DNA binding	IEA Inferred from Electronic Annotation more info
positive regulation of cell death	IEA Inferred from Electronic Annotation more info
positive regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of insulin secretion involved in cellular response to glucose stimulus	IEA Inferred from Electronic Annotation more info
positive regulation of transcription from RNA polymerase II promoter	ISS Inferred from Sequence or Structural Similarity more info
response to alkaloid	IEA Inferred from Electronic Annotation more info
response to chlorate	IEA Inferred from Electronic Annotation more info
response to cytokine	IEA Inferred from Electronic Annotation more info
response to drug	IEA Inferred from Electronic Annotation more info
response to fatty acid	IEA Inferred from Electronic Annotation more info
response to glucocorticoid	IEA Inferred from Electronic Annotation more info
response to iron(II) ion	IEA Inferred from Electronic Annotation more info
response to leucine	IEA Inferred from Electronic Annotation more info
response to nicotine	IEA Inferred from Electronic Annotation more info
response to vitamin	IEA Inferred from Electronic Annotation more info
response to wounding	IEA Inferred from Electronic Annotation more info
smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
stem cell differentiation	IEA Inferred from Electronic Annotation more info
transcription from RNA polymerase II promoter	IEA Inferred from Electronic Annotation more info
transdifferentiation	IEA Inferred from Electronic Annotation more info
type B pancreatic cell differentiation	IDA Inferred from Direct Assay more info	PubMed
type B pancreatic cell differentiation	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
cytosol	IEA Inferred from Electronic Annotation more info
nuclear speck	IEA Inferred from Electronic Annotation more info
nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: pancreas/duodenum homeobox protein 1

Names: IPF-1; IUF-1; glucose-sensitive factor; insulin promoter factor 1, homeodomain transcription factor; insulin upstream factor 1; islet/duodenum homeobox-1; pancreatic-duodenal homeobox factor 1; somatostatin transcription factor 1; somatostatin-transactivating factor 1

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.