GeneBe

PTF1A

protein-coding

pancreas associated transcription factor 1a, the group of Basic helix-loop-helix proteins|PTF1 complex

Gene summary

This gene encodes a protein that is a component of the pancreas transcription factor 1 complex (PTF1) and is known to have a role in mammalian pancreatic development. The protein plays a role in determining whether cells allocated to the pancreatic buds continue towards pancreatic organogenesis or revert back to duodenal fates. The protein is thought to be involved in the maintenance of exocrine pancreas-specific gene expression including elastase 1 and amylase. Mutations in this gene cause cerebellar agenesis and loss of expression is seen in ductal type pancreas cancers. [provided by RefSeq, Jul 2008]

MANE transcript

NM_178161.3

Inheritance

AR

ClinVar variants

P:8U:74B:65

Top phenotype

Pancreatic and cerebellar agenesis; Pancreatic agenesis 2

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr10:23,192,312-23,194,245

External References & Databases

Ensembl (ENSG00000168267)NCBI Gene (256297)OMIM (607194)HGNC:23734GenCCUniProt (Q7RTS3)AlphaFoldClinVar (PTF1A)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~1.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012192

Submitter: PanelApp Australia

pancreatic agenesis 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014406

Submitter: PanelApp Australia

permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012192

Submitter: Labcorp Genetics (formerly Invitae)

permanent neonatal diabetes mellitusSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100164

Submitter: Genomics England PanelApp

pancreatic agenesis 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014406

Submitter: G2P

pancreatic agenesis 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014406

Submitter: Genomics England PanelApp

pancreatic agenesis 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014406

Submitter: Labcorp Genetics (formerly Invitae)

permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012192

Submitter: G2P

pancreatic agenesisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009832

Submitter: Orphanet

permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012192

Submitter: Orphanet

permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0012192

Submitter: Ambry Genetics

permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012192

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Pancreatic and cerebellar agenesis; Pancreatic agenesis 2AR

Manifestation: Craniofacial; Gastrointestinal; Neurologic; Ophthalmologic

Intervention: Endocrine

Rationale: As the conditions can include pancreatic insufficiency, awareness can allow measures to manage neonatal diabetes as well as pancreatic exocrine insufficiency

Refs: 10507728; 15543146; 19650412; 21749365; 24212882Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTF1A variants in ClinVar

12 Conditions Cataloged
not providedTotal: 82
Inborn genetic diseasesTotal: 54
Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndromeTotal: 29
Pancreatic agenesis 2Total: 13
not specifiedTotal: 10
PTF1A-related disorderTotal: 9
Monogenic diabetesTotal: 7
Neonatal insulin-dependent diabetes mellitusTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178161.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
56
clinvar
 56
missense
1
clinvar
72
clinvar
9
clinvar
 82
nonsense
1
clinvar
1
clinvar
 2
start loss
0
frameshift
2
clinvar
2
clinvar
2
clinvar
 6
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total4474650147

Highest pathogenic variant AF is 0.000007719146

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_178161.3RefSeqNP_835455.12MANE Select
ENST00000376504.4EnsemblENSP00000365687.32MANE Select
ENST00000638469.1EnsemblENSP00000491649.12Standard
ENST00000639082.1EnsemblENSP00000492481.12Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
ptf1aDanio rerio

Structure: retinal ganglion cell

Quality: absent

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • PTF1A related regulatory pathway
  • Notch-mediated HES/HEY network

Biological Process

  • regulation of transcription, DNA-templated
  • tissue development
  • retina layer formation
  • cerebellum development
  • pancreas development

Molecular Function

  • RNA polymerase II distal enhancer sequence-specific DNA binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • DNA-binding transcription activator activity, RNA polymerase II-specific
  • DNA binding
  • chromatin binding

Cellular Component

  • nucleus
  • transcription factor complex
  • cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000376504
Coding exons
2
Length
1926
Individuals with no LoFs
125742
Homozygous LoFs
0
Heterozygous LoFs
3
Defined
125745
p
0.0000119
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.508881020.8590.000004842021
Missense (PolyPhen)1213.0480.91967154
Synonymous-1.085848.41.200.00000238722
Loss of Function1.5726.230.3212.78e-797

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000680.000062rare
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.00000880.0000088rare
South Asian0.0000340.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Transcription factor implicated in the cell fate determination in various organs. Binds to the E-box consensus sequence 5'-CANNTG-3'. Plays a role in early and late pancreas development and differentiation. Important for determining whether cells allocated to the pancreatic buds continue towards pancreatic organogenesis or revert back to duodenal fates. May be involved in the maintenance of exocrine pancreas-specific gene expression including ELA1 and amylase. Required for the formation of pancreatic acinar and ductal cells. Plays an important role in cerebellar development. Directly regulated by FOXN4 and RORC during retinal development, FOXN4-PTF1A pathway plays a central role in directing the differentiation of retinal progenitors towards horizontal and amacrine fates. {ECO:0000269|PubMed:10768861, ECO:0000269|PubMed:15543146}.;
Disease
DISEASE: Pancreatic agenesis 2 (PAGEN2) [MIM:615935]: 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:24212882}. Note=The disease is caused by mutations affecting the gene represented in this entry. In some families with pancreatic agenesis, disease causing mutations affect the sequence and activity of an enhancer region of 400-bp located 25 kb downstream of PTF1A (PubMed:24212882). {ECO:0000269|PubMed:24212882}.;

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.335

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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