PDX1

Chr 13

pancreatic and duodenal homeobox 1

Also known as: GSF, IDX-1, IPF1, IUF1, MODY4, PAGEN1, PDX-1, STF-1

NCBI Gene: 3651 ENSG00000139515 UniProt: P52945

PDX1 encodes a transcriptional activator that regulates insulin, somatostatin, glucokinase, and glucose transporter genes and is essential for pancreatic development and maintaining beta-cell function. Mutations cause pancreatic agenesis with early-onset insulin-dependent diabetes mellitus and maturity-onset diabetes of the young type 4 (MODY4). Inheritance can be either autosomal dominant or autosomal recessive depending on the specific variant and phenotype severity.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPancreatic agenesis 1

UniProtType 2 diabetes mellitus

UniProtMaturity-onset diabetes of the young 4

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

242

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.05

LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — PDX1

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.018

Z-score 1.47

OE 0.46 (0.23–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.27Z-score

OE missense 1.06 (0.93–1.21)

167 obs / 157.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.46 (0.23–1.05)

0≤0.351.4

Missense OE?1.06 (0.93–1.21)

0≤0.61.4

Synonymous OE?1.41

0≤1.21.6

LoF obs/exp: 4 / 8.7Missense obs/exp: 167 / 157.6Syn Z: -2.81

Background carrier burden — how many people carry a rare variant somewhere in PDX1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

488 rare PASS variants

Rare truncating (LoF)

1 in 3,300

49 rare PASS variants

Rare synonymous (reference)

1 in 170

249 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PDX1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 4,200
South Asian	~43k	1 in 82	1 in 3,300
Remaining (unassigned)	~30k	1 in 92	1 in 3,200
European (Finnish)	~27k	1 in 200	1 in 5,300
Admixed American	~22k	1 in 120	1 in 3,100
African / African American	~21k	1 in 86	1 in 1,500
East Asian	~20k	1 in 140	1 in 1,600
Ashkenazi Jewish	~13k	1 in 490	≈ 1 in 11,000
Middle Eastern	~2,884	1 in 87	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓