PTF1A

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

Basic information

Region (hg38): 10:23192312-23194245

Links

ENSG00000168267 ∙ NCBI:256297 ∙ OMIM:607194 ∙ HGNC:23734 ∙ Uniprot:Q7RTS3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome (Definitive), mode of inheritance: AR
• permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome (Strong), mode of inheritance: AR
• permanent neonatal diabetes mellitus (Strong), mode of inheritance: AR
• pancreatic agenesis 2 (Strong), mode of inheritance: AR
• permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome (Moderate), mode of inheritance: AR
• permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome (Strong), mode of inheritance: AR
• pancreatic agenesis (Supportive), mode of inheritance: AR
• permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome (Supportive), mode of inheritance: AR
• pancreatic agenesis 2 (Strong), mode of inheritance: AR
• permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pancreatic and cerebellar agenesis; Pancreatic agenesis 2	AR	Endocrine	As the conditions can include pancreatic insufficiency, awareness can allow measures to manage neonatal diabetes as well as pancreatic exocrine insufficiency	Craniofacial; Gastrointestinal; Neurologic; Ophthalmologic	10507728; 15543146; 19650412; 21749365; 24212882

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PTF1A gene.

• Maturity onset diabetes mellitus in young (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTF1A 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				31		31
missense		1	43	4		48
nonsense						0
start loss						0
frameshift	1	1	1			3
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding			8	2	4	14
Total	2	2	54	37	4

Highest pathogenic variant AF is 0.00000667

Variants in PTF1A

This is a list of pathogenic ClinVar variants found in the PTF1A region.

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

Position	Type	Phenotype	Significance	ClinVar
10-23192538-C-T		Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome • Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome;Pancreatic agenesis 2	Uncertain significance (Jul 15, 2022)
10-23192574-C-T		Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome • Pancreatic agenesis 2;Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome	Conflicting classifications of pathogenicity (May 20, 2023)
10-23192611-C-T			Likely benign (Jun 16, 2023)
10-23192612-A-C		Inborn genetic diseases	Uncertain significance (Apr 25, 2023)
10-23192623-T-G			Likely benign (Nov 10, 2023)
10-23192632-C-T		Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome	Benign/Likely benign (Jun 03, 2023)
10-23192635-C-G			Likely benign (Sep 15, 2021)
10-23192645-G-A		Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome	Uncertain significance (Jan 13, 2018)
10-23192657-C-A		Inborn genetic diseases	Uncertain significance (Nov 17, 2023)
10-23192662-G-T			Likely benign (Jun 13, 2022)
10-23192663-G-T			Uncertain significance (Mar 18, 2022)
10-23192682-A-G		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
10-23192692-C-T		Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome • Neonatal insulin-dependent diabetes mellitus	Conflicting classifications of pathogenicity (Jan 31, 2024)
10-23192702-C-T		Inborn genetic diseases	Uncertain significance (Apr 04, 2024)
10-23192716-C-T			Likely benign (Apr 21, 2022)
10-23192717-C-T			Uncertain significance (Dec 06, 2021)
10-23192720-G-A		Inborn genetic diseases	Uncertain significance (Jun 16, 2024)
10-23192728-G-C			Likely benign (Aug 03, 2022)
10-23192731-C-T		Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome	Conflicting classifications of pathogenicity (May 19, 2022)
10-23192732-C-T			Likely benign (Aug 11, 2023)
10-23192737-G-A			Likely benign (Dec 31, 2019)
10-23192749-G-C			Likely benign (Jun 13, 2018)
10-23192755-G-T			Likely benign (Dec 17, 2020)
10-23192759-G-A		Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome	Likely benign (May 02, 2023)
10-23192770-G-T			Likely benign (Jan 09, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTF1A	protein_coding	protein_coding	ENST00000376504	2	1926

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.166	0.778	125742	0	3	125745	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.508	88	102	0.859	0.00000484	2021
Missense in Polyphen		12	13.048	0.91967		154
Synonymous	-1.08	58	48.4	1.20	0.00000238	722
Loss of Function	1.57	2	6.23	0.321	2.78e-7	97

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000683	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000340	0.0000327
Other	0.00	0.00

dbNSFP

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}.
• Pathway: PTF1A related regulatory pathway;Notch-mediated HES/HEY network (Consensus)

Haploinsufficiency Scores

• pHI: 0.193
• ghis: 0.406

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.335

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ptf1a
• Phenotype: digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; skeleton phenotype; embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal 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); endocrine/exocrine gland phenotype; neoplasm; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: ptf1a
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: regulation of transcription, DNA-templated;tissue development;retina layer formation;cerebellum development;pancreas development;exocrine pancreas development;amacrine cell differentiation;positive regulation of transcription by RNA polymerase II;retinoic acid receptor signaling pathway;neuron fate commitment;regulation of neural retina development
• Cellular component: nucleus;transcription factor complex;cytoplasm
• 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;protein dimerization activity;E-box binding