PTF1A (pancreas associated transcription factor 1a)

Gene

• Entrez ID: 256297
• Gene name: Pancreas associated transcription factor 1a
• Gene symbol: PTF1A
• Synonyms (NCBI Gene): PACA, PAGEN2, PTF1-p48, bHLHa29, p48
• Chromosome: 10
• Chromosome location: 10p12.2
• 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 c

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894186	C>T	Pathogenic	Stop gained, coding sequence variant
rs140097468	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs535090775	G>C,T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs886039746	G>-,GG	Pathogenic	Coding sequence variant, frameshift variant
rs1588563037	C>A	Pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1272582	hsa-miR-501-3p	CLIP-seq
MIRT1272583	hsa-miR-502-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IEA
GO:0003677	Function	DNA binding	IEA
GO:0003677	Function	DNA binding	ISS
GO:0003682	Function	Chromatin binding	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	ISS
GO:0005667	Component	Transcription regulator complex	IEA
GO:0005667	Component	Transcription regulator complex	ISS
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	ISS
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	ISS
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006366	Process	Transcription by RNA polymerase II	IEA
GO:0007399	Process	Nervous system development	IEA
GO:0009888	Process	Tissue development	IDA	12185368
GO:0010842	Process	Retina layer formation	IEA
GO:0010842	Process	Retina layer formation	ISS
GO:0021549	Process	Cerebellum development	IEA
GO:0021549	Process	Cerebellum development	IMP	15543146
GO:0021953	Process	Central nervous system neuron differentiation	IEA
GO:0030154	Process	Cell differentiation	IEA
GO:0030902	Process	Hindbrain development	IEA
GO:0031016	Process	Pancreas development	IEA
GO:0031016	Process	Pancreas development	IMP	15543146
GO:0031017	Process	Exocrine pancreas development	IEA
GO:0031017	Process	Exocrine pancreas development	ISS
GO:0032502	Process	Developmental process	IBA
GO:0035881	Process	Amacrine cell differentiation	IEA
GO:0035881	Process	Amacrine cell differentiation	ISS
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0045165	Process	Cell fate commitment	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0046983	Function	Protein dimerization activity	IEA
GO:0048384	Process	Retinoic acid receptor signaling pathway	IEA
GO:0048663	Process	Neuron fate commitment	IEA
GO:0048699	Process	Generation of neurons	IEA
GO:0060042	Process	Retina morphogenesis in camera-type eye	IEA
GO:0061074	Process	Regulation of neural retina development	IEA
GO:0061074	Process	Regulation of neural retina development	ISS
GO:0070888	Function	E-box binding	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 607194
• HGNC: 23734
• e!Ensembl: ENSG00000168267

Protein

• UniProt ID: Q7RTS3
• Protein name: Pancreas transcription factor 1 subunit alpha (Class A basic helix-loop-helix protein 29) (bHLHa29) (Pancreas-specific transcription factor 1a) (bHLH transcription factor p48) (p48 DNA-binding subunit of transcription factor PTF1) (PTF1-p48)
• Protein 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 cell
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00010	HLH	164 → 216	Helix-loop-helix DNA-binding domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Pancreas-specific (at protein level). Loss of expression is seen in ductal type pancreas cancers. {ECO:0000269|PubMed:10768861}.
• Sequence:

  MDAVLLEHFPGGLDAFPSSYFDEDDFFTDQSSRDPLEDGDELLADEQAEVEFLSHQLHEY
  CYRDGACLLLQPAPPAAPLALAPPSSGGLGEPDDGGGGGYCCETGAPPGGFPYSPGSPPS
  CLAYPCAGAAVLSPGARLRGLSGAAAAAARRRRRVRSEAELQQLRQAANVRERRRMQSIN
  DAFEGLRSHIPTLPYEKRLSKVDTLRLAIGYINFLSELVQADLPLRGGGAGGCGGPGGGG
  RLGGDSPGSQAQKVIICHRGTRSPSPSDPDYGLPPLAGHSLSWTDEKQLKEQNIIRTAKV
  WTPEDPRKLNSKSSFNNIENEPPFEFVS

• Sequence length: 328

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Kallikrein, decreased urinary activity of	Likely pathogenic; Pathogenic	rs1588563037	RCV003225135	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Maturity-onset diabetes of the young	Pathogenic	rs868849369	RCV003323322	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pancreatic agenesis 2	Likely pathogenic; Pathogenic	rs1588563037	RCV000984966	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome	Pathogenic; Likely pathogenic	rs104894186, rs886039746, rs2492671663, rs1588563037	RCV000003594 RCV000003595 RCV000023626 RCV003227879	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CEREBELLAR DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS, PERMANENT NEONATAL	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS, PERMANENT NEONATAL, WITH CEREBELLAR AGENESIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MATURITY ONSET DIABETES MELLITUS IN YOUNG	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Monogenic diabetes	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neonatal insulin-dependent diabetes mellitus	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pancreatic beta cell agenesis with neonatal diabetes mellitus	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
PARTIAL PANCREATIC AGENESIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Permanent neonatal diabetes mellitus	Conflicting classifications of pathogenicity; Uncertain significance; Benign; Likely benign	ClinVar GenCC	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
PTF1A-related disorder	Benign; Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Type 2 diabetes mellitus	Benign	ClinVar GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Promyelocytic Leukemia	Promyelocytic Leukemia	BEFREE	10694514, 9186002		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	Pubtator	32893856	Associate	★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
ANOPHTHALMIA AND PULMONARY HYPOPLASIA	Syndromic microphthalmia	BEFREE	21984419, 26151762, 29719936, 30728464		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	26081906		★☆☆☆☆ Found in Text Mining only
Cerebellar agenesis	Cerebellar agenesis	BEFREE	18513948		★☆☆☆☆ Found in Text Mining only
Cerebellar agenesis	Cerebellar agenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar Diseases	CTD_human_DG	15543146, 19650412		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cerebellar Hypoplasia	Cerebellar Hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cholestasis	Cholelithiasis	Pubtator	32893856	Associate	★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of pancreas	Pancreatic hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
DEND syndrome	DEND Syndrome	BEFREE	28943513		★☆☆☆☆ Found in Text Mining only
Developmental Delay, Epilepsy, and Neonatal Diabetes	Developmental delay	BEFREE	28943513		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	32893856	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	26184423		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	26184423		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	28943513, 29624227, 32893856, 37897565	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Permanent Neonatal	Neonatal diabetes mellitus	Pubtator	25755231, 31441606	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Permanent Neonatal with Cerebellar Agenesis	Diabetes mellitus permanent neonatal	Pubtator	27284104, 28663161	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Transient Neonatal 1	Diabetes mellitus transient neonatal	Pubtator	27284104, 28663161, 28943513, 29624227, 37897565	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 1	Diabetes mellitus, type 1	Pubtator	29624227	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	29302047		★☆☆☆☆ Found in Text Mining only
DIABETES MELLITUS, PERMANENT NEONATAL	Diabetes Mellitus	BEFREE	25755231		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dysmorphism	Dysmorphism	BEFREE	18513948		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	21098709, 26081906		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	21098709, 26081906		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	21098709		★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	32893856	Associate	★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	Pubtator	29624227	Associate	★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of the optic nerve	Hypoplasia Of The Optic Nerve	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lymphohistiocytosis, Hemophagocytic	Lymphohistiocytosis	BEFREE	28571517		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	10768861, 23237571, 26762195, 28697176, 28872120, 30016349, 31422917		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	10882109, 31841696		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neonatal diabetes mellitus	Diabetes Mellitus	BEFREE	25755231, 26184423		★☆☆☆☆ Found in Text Mining only
Neonatal diabetes mellitus	Diabetes Mellitus	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	10768861, 19715403, 2199964, 25154617, 26081906, 29248441, 29719936		★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural Tube Defect	BEFREE	25775927		★☆☆☆☆ Found in Text Mining only
Pancreatic Agenesis, Congenital	Congenital Pancreatic Agenesis	CTD_human_DG	15543146, 24212882		★☆☆☆☆ Found in Text Mining only
Pancreatic Agenesis, Congenital	Congenital Pancreatic Agenesis	ORPHANET_DG	24212882		★☆☆☆☆ Found in Text Mining only
PANCREATIC AND CEREBELLAR AGENESIS	PANCREATIC AND CEREBELLAR AGENESIS	GENOMICS_ENGLAND_DG	10507728, 15543146, 19650412, 24212882		★☆☆☆☆ Found in Text Mining only
PANCREATIC AND CEREBELLAR AGENESIS	PANCREATIC AND CEREBELLAR AGENESIS	BEFREE	15543146, 30470852		★☆☆☆☆ Found in Text Mining only
PANCREATIC AND CEREBELLAR AGENESIS	PANCREATIC AND CEREBELLAR AGENESIS	ORPHANET_DG	15543146		★☆☆☆☆ Found in Text Mining only
PANCREATIC AND CEREBELLAR AGENESIS	PANCREATIC AND CEREBELLAR AGENESIS	CTD_human_DG	15543146, 19650412		★☆☆☆☆ Found in Text Mining only
PANCREATIC AND CEREBELLAR AGENESIS	PANCREATIC AND CEREBELLAR AGENESIS	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	23237571, 26762195, 28697176, 28872120, 30016349, 31422917		★☆☆☆☆ Found in Text Mining only
Pancreatic Ductal Adenocarcinoma	Pancreatic adenocarcinoma	BEFREE	26151762, 29719936		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasm	Pancreatic Neoplasm	BEFREE	25311989		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	29624227, 34581719	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatitis	Pancreatitis	Pubtator	27284104	Associate	★☆☆☆☆ Found in Text Mining only
Patent ductus arteriosus	Patent ductus arteriosus	BEFREE	25311989		★☆☆☆☆ Found in Text Mining only
Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome	Diabetes Mellitus-Pancreatic And Cerebellar Agenesis Syndrome	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
VATER/VACTERL ASSOCIATION	VACTERL ASSOCIATION	BEFREE	25775927		★☆☆☆☆ Found in Text Mining only
Xeroderma Pigmentosum	Xeroderma Pigmentosum	BEFREE	10882109		★☆☆☆☆ Found in Text Mining only
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP E	Xeroderma Pigmentosum	BEFREE	10882109, 8798680, 9632823, 9892649		★☆☆☆☆ Found in Text Mining only