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
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]
Expression: Biased expression in duodenum (RPKM 9.6), stomach (RPKM 1.5) and 3 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 13q12.2

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	13	NC_000013.11 (27919982..27926313)
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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The unusual presentation in this Brazilian family enabled expansion upon a rare disease phenotype, demonstrating the possibility of detecting pancreatic malformation even in cases of PDX1 -related diabetes diagnosed after the first year of life. This finding can improve the management of MODY4 patients, leading to precocious investigation of pancreatic dysgenesis and exocrine dysfunction.
Title: PDX1 -MODY and dorsal pancreatic agenesis: New phenotype of a rare disease.
heat shock proteins are involved in PDX1-mediated effects on the genesis of gastric cancer
Title: Potential involvement of heat shock proteins in pancreatic-duodenal homeobox-1-mediated effects on the genesis of gastric cancer: A 2D gel-based proteomic study.
Investigated the effect of gestational diabetes mellitus (GDM) on the expression and methylation of PGC-1alpha and PDX1 in placenta and their effects on fetal glucose metabolism. Blood glucose was negatively correlated with the expression of PGC-1alpha and PDX1 mRNA in the placenta.
Title: Altered expression of PGC-1α and PDX1 and their methylation status are associated with fetal glucose metabolism in gestational diabetes mellitus.
PDX1, Neurogenin-3, and MAFA are critical transcription regulators for beta cell development and regeneration. (Review)
Title: PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration.
study provides a novel culture protocol for generating pancreas-committed cells from hAECs and reveals an interplay between Pdx1 and activin A/nicotinamide signaling in early pancreatic fate determination.
Title: Combinations of Activin A or Nicotinamide with the Pancreatic Transcription Factor PDX1 Support Differentiation of Human Amnion Epithelial Cells Toward a Pancreatic Lineage.
Data indicate the secretory granule membrane glycoprotein 2 as a marker for PDX1+/NKX6-1+ pancreatic progenitors (PPs).
Title: Glycoprotein 2 is a specific cell surface marker of human pancreatic progenitors.
expression of regulatory master genes of embryonic development in pancreatic cancer cells on the intracellular concentration of the master regulator PDX1
Title: Dependence of expression of regulatory master genes of embryonic development in pancreatic cancer cells on the intracellular concentration of the master regulator PDX1.
Efficiency of differentiation of Induced pluripotent stem cells to insulin producing cells can be increased by concurrent expression of PDX1 and NKX6.1 during progenitor cells maturation.
Title: Directed differentiation of human iPSC into insulin producing cells is improved by induced expression of PDX1 and NKX6.1 factors in IPC progenitors.
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.

Submit: New GeneRIF Correction See all GeneRIFs (120)

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: Maturity-Onset Diabetes of the Young Overview	Compare labs
Pancreatic agenesis, congenital MedGen: C3891828 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: 259 organisms have orthologs with human gene PDX1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA-binding transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA-binding transcription factor activity	TAS Traceable Author Statement more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
DNA-binding transcription factor activity, RNA polymerase II-specific	ISM Inferred from Sequence Model more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
RNA polymerase II proximal promoter sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
promoter-specific chromatin binding	IEA Inferred from Electronic Annotation more info
protein heterodimerization activity	IEA Inferred from Electronic Annotation more info
protein-containing complex binding	IEA Inferred from Electronic Annotation more info
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
endocrine pancreas development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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 by RNA polymerase II	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 by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of transcription by RNA polymerase II	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 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 by RNA polymerase II	IEA Inferred from Electronic Annotation more info
transdifferentiation	IEA Inferred from Electronic Annotation more info
type B pancreatic cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed

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.