PDX1

pancreatic and duodenal homeobox 1, the group of HOXL subclass homeoboxes

Basic information

Region (hg38): 13:27920000-27926313

Previous symbols: [ "IPF1" ]

Links

ENSG00000139515 ∙ NCBI:3651 ∙ OMIM:600733 ∙ HGNC:6107 ∙ Uniprot:P52945 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• maturity-onset diabetes of the young type 4 (Strong), mode of inheritance: AR
• permanent neonatal diabetes mellitus (Strong), mode of inheritance: AR
• pancreatic agenesis 1 (Strong), mode of inheritance: AR
• maturity-onset diabetes of the young type 4 (Definitive), mode of inheritance: AD
• pancreatic agenesis 1 (Moderate), mode of inheritance: AR
• pancreatic agenesis (Supportive), mode of inheritance: AR
• maturity-onset diabetes of the young (Supportive), mode of inheritance: AD
• permanent neonatal diabetes mellitus (Supportive), mode of inheritance: AD
• maturity-onset diabetes of the young type 4 (Strong), mode of inheritance: AD
• pancreatic agenesis 1 (Strong), mode of inheritance: AR
• monogenic diabetes (Moderate), mode of inheritance: AD
• pancreatic agenesis 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pancreatic agenesis 1; Neonatal diabetes mellitus	AR	Endocrine; Gastrointestinal	Individuals may manifest in infancy with findings including intrauterine growth retardation, postnatal growth deficiency, and signs of diabetes mellitus (eg, hyperglycemia, glycosuria), as well as severe dehydration, and recognition can allow preventive measures related to potential sequelae, surveillance (eg, with blood glucose monitoring as well as surveillance for other common sequelae of diabetes mellitus affecting systems such as the renal and ophthalmogic systems); In the case of an acute diabetic crisis, rapid treatment (eg, with rehydration and IV insulin, transitioning to SQ insulin when stable) is indicated, though rapid-acting and (non-continuous) short-acting insulin preparations may result in severe hypoglycemia in young patients; Due to exocrine (as well as endocrine) pancreatic insufficiency, some individuals may benefit from enzymatic replacement	Biochemical; Endocrine; Gastrointestinal; Neurologic	8506821; 8988180; 9326926; 9399911; 9649577; 10545531; 10545530; 10720084; 11575290; 11935326; 12970316; 19496967; 20009086; 20301620; 20546293; 20621032; 21521318; 21937992; 22124438; 23320570; 25087164

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDX1 gene.

• Maturity-onset diabetes of the young type 4;Pancreatic agenesis 1 (1 variants)
• Permanent neonatal diabetes mellitus (1 variants)
• Pancreatic agenesis 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDX1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	37	1	42
missense	1	5	59	1		66
nonsense			3			3
start loss						0
frameshift		5	3			8
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			3	4	6	13
Total	1	10	73	42	7

Variants in PDX1

This is a list of pathogenic ClinVar variants found in the PDX1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
13-27920029-AG-A			Benign (Nov 18, 2020)
13-27920053-G-T			Likely benign (Sep 04, 2018)
13-27920088-ACTCCCGG-A		not specified	Likely benign (Feb 01, 2018)
13-27920088-A-ACTCCCGG		Maturity-onset diabetes of the young type 4	Uncertain significance (Aug 18, 2011)
13-27920103-CTCCCGGCTCCCGGT-C		PDX1-related disorder	Uncertain significance (Dec 07, 2023)
13-27920114-C-T		PDX1-related disorder	Likely benign (Jul 28, 2023)
13-27920121-C-T		Maturity-onset diabetes of the young type 4 • not specified	Conflicting classifications of pathogenicity (Mar 25, 2021)
13-27920144-C-T		Maturity onset diabetes mellitus in young	Benign/Likely benign (Jan 01, 2024)
13-27920146-G-C		Pancreatic hypoplasia • Type 2 diabetes mellitus;Maturity-onset diabetes of the young type 4;Pancreatic agenesis 1 • not specified	Uncertain significance (Jun 25, 2023)
13-27920166-G-A		not specified • Monogenic diabetes • Maturity-onset diabetes of the young type 4 • Maturity onset diabetes mellitus in young	Uncertain significance (Oct 25, 2022)
13-27920185-A-T			Uncertain significance (Apr 17, 2021)
13-27920190-T-C		Type 2 diabetes mellitus • Type 2 diabetes mellitus;Maturity-onset diabetes of the young type 4;Pancreatic agenesis 1 • Diabetes mellitus type 2, susceptibility to	Uncertain significance (Nov 07, 2023)
13-27920195-G-C			Likely benign (Aug 29, 2022)
13-27920200-A-T			Uncertain significance (Jan 05, 2023)
13-27920215-C-T		Pancreatic hypoplasia	Uncertain significance (-)
13-27920220-T-G		Pancreatic hypoplasia	Uncertain risk allele (-)
13-27920230-G-A			Uncertain significance (May 17, 2022)
13-27920235-C-A		not specified • Maturity-onset diabetes of the young type 4 • Monogenic diabetes • Type 2 diabetes mellitus • Maturity onset diabetes mellitus in young	Conflicting classifications of pathogenicity (Aug 28, 2024)
13-27920235-C-G		not specified • Type 2 diabetes mellitus;Maturity-onset diabetes of the young type 4	Conflicting classifications of pathogenicity (Sep 19, 2023)
13-27920235-C-T		not specified	Uncertain significance (Aug 30, 2023)
13-27920236-C-A		Maturity-onset diabetes of the young type 4;Pancreatic agenesis 1;Type 2 diabetes mellitus	Uncertain significance (Sep 20, 2023)
13-27920237-T-C			Likely benign (Jun 23, 2018)
13-27920239-C-T		not specified	Uncertain significance (Feb 13, 2023)
13-27920240-G-A			Uncertain significance (Jul 08, 2022)
13-27920245-T-G		Maturity-onset diabetes of the young type 4;Type 2 diabetes mellitus	Uncertain significance (Aug 16, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDX1	protein_coding	protein_coding	ENST00000381033	2	6212

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0178	0.901	125549	0	8	125557	0.0000319

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.266	167	158	1.06	0.00000714	1757
Missense in Polyphen		41	49.592	0.82674		561
Synonymous	-2.81	106	75.0	1.41	0.00000360	615
Loss of Function	1.47	4	8.69	0.460	3.71e-7	95

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000716	0.0000617
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000552	0.0000529
Middle Eastern	0.00	0.00
South Asian	0.0000343	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Activates insulin, somatostatin, glucokinase, islet amyloid polypeptide and glucose transporter type 2 gene transcription. Particularly involved in glucose-dependent regulation of insulin gene transcription. As part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. Binds preferentially the DNA motif 5'-[CT]TAAT[TG]-3'. During development, specifies the early pancreatic epithelium, permitting its proliferation, branching and subsequent differentiation. At adult stage, required for maintaining the hormone-producing phenotype of the beta-cell.
• Disease: DISEASE: Pancreatic agenesis 1 (PAGEN1) [MIM:260370]: A disease characterized by isolated hypoplasia or agenesis of the pancreas, pancreatic beta-cell failure resulting in neonatal insulin- dependent diabetes mellitus, and exocrine pancreatic insufficiency. {ECO:0000269|PubMed:8988180}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Maturity-onset diabetes of the young 4 (MODY4) [MIM:606392]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. {ECO:0000269|PubMed:9326926}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Type II diabetes mellitus - Homo sapiens (human);Maturity onset diabetes of the young - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;Type II diabetes mellitus;PTF1A related regulatory pathway;FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

• pRec: 0.603

Haploinsufficiency Scores

• pHI: 0.187
• hipred: Y
• hipred_score: 0.697
• ghis: 0.438

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.683

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pdx1
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; digestive/alimentary phenotype; renal/urinary system phenotype; immune system phenotype; liver/biliary system phenotype

Zebrafish Information Network

• Gene name: pdx1
• Affected structure: acinar cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;liver development;type B pancreatic cell differentiation;glucose metabolic process;generation of precursor metabolites and energy;transcription by RNA polymerase II;nitric oxide mediated signal transduction;positive regulation of cell population proliferation;negative regulation of cell population proliferation;animal organ morphogenesis;morphogenesis of embryonic epithelium;insulin secretion;exocrine pancreas development;endocrine pancreas development;positive regulation of insulin secretion involved in cellular response to glucose stimulus;glucose homeostasis;positive regulation of transcription by RNA polymerase II;digestive tract development;detection of glucose;negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway;negative regulation of type B pancreatic cell apoptotic process
• Cellular component: nucleus;nucleoplasm;cytosol;nuclear speck
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity