PTF1A

Summary

PTF1A (pancreas associated transcription factor 1a, HGNC:23734) is a protein-coding gene on chromosome 10p12.2, encoding Pancreas transcription factor 1 subunit alpha (Q7RTS3). Transcription factor implicated in the cell fate determination in various organs.

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.

Source: NCBI Gene 256297 — RefSeq curated summary.

At a glance

• Gene–disease (curated): permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 170 total — 5 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 39
• Transcription factor: yes — 18 downstream targets (CollecTRI)
• MANE Select transcript: NM_178161

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23734
Approved symbol	PTF1A
Name	pancreas associated transcription factor 1a
Location	10p12.2
Locus type	gene with protein product
Status	Approved
Aliases	PTF1-p48, bHLHa29, p48
Ensembl gene	ENSG00000168267
Ensembl biotype	protein_coding
OMIM	607194
Entrez	256297

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000376504, ENST00000638469, ENST00000639082, ENST00000639873, ENST00000640579, ENST00000640697

RefSeq mRNA: 1 — MANE Select: NM_178161 NM_178161

CCDS: CCDS7143

Canonical transcript exons

ENST00000376504 — 2 exons

Exon	Start	End
ENSE00001470737	23193704	23194245
ENSE00001470744	23192312	23193314

Expression profiles

Bgee: expression breadth broad, 96 present calls, max score 97.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3684 / max 377.1963, expressed in 29 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104272	0.3574	29
205786	0.0111	4

Top tissues by expression

121 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	97.58	gold quality
pancreas	UBERON:0001264	87.36	gold quality
islet of Langerhans	UBERON:0000006	67.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	67.03	gold quality
body of stomach	UBERON:0001161	60.14	gold quality
right testis	UBERON:0004534	59.16	gold quality
left testis	UBERON:0004533	58.96	gold quality
testis	UBERON:0000473	58.81	gold quality
stomach	UBERON:0000945	58.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	58.28	gold quality
fundus of stomach	UBERON:0001160	58.27	gold quality
putamen	UBERON:0001874	57.72	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	57.09	gold quality
nucleus accumbens	UBERON:0001882	56.92	gold quality
right frontal lobe	UBERON:0002810	56.79	gold quality
frontal cortex	UBERON:0001870	54.32	gold quality
cerebral cortex	UBERON:0000956	54.29	gold quality
caudate nucleus	UBERON:0001873	54.18	gold quality
anterior cingulate cortex	UBERON:0009835	54.17	gold quality
apex of heart	UBERON:0002098	52.91	gold quality
prefrontal cortex	UBERON:0000451	52.66	gold quality
primary visual cortex	UBERON:0002436	52.58	gold quality
superior frontal gyrus	UBERON:0002661	51.85	gold quality
Ammon’s horn	UBERON:0001954	50.92	gold quality
brain	UBERON:0000955	50.02	gold quality
hypothalamus	UBERON:0001898	47.69	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	46.25	gold quality
right uterine tube	UBERON:0001302	46.06	silver quality
right hemisphere of cerebellum	UBERON:0014890	44.88	gold quality
temporal lobe	UBERON:0001871	44.83	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	799.72
E-ANND-3	yes	15.30

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

18 targets.

Target	Regulation
ATOH7	Repression
CEL	Unknown
CPA1	Activation
GAL	Unknown
GAST
KAT2B
MIB1
NPY	Unknown
PDX1
PDYN	Unknown
PENK	Unknown
PNOC	Unknown
PPDPF
PRDM13
PTF1A
SST	Activation
TLX1
TLX3

Upstream regulators (CollecTRI, top): ASCL1, FOXN4, PRDM13, PTF1A, RBPJ, RBPJL

miRNA regulators (miRDB)

37 targeting PTF1A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-873-5P	98.84	66.90	1348

Literature-anchored findings (GeneRIF, showing 18)

• P48 interacts with the RBP-L and RBP-J subunits primarily through two short conserved tryptophan-containing motifs, similar to the motif of the Notch intracellular domain (NotchIC) that interacts with RBP-J. (PMID:16354684)
• Controls the fate, survival, differentiation, and migration of climbing fiber neurons during their development in the transgenic murine inferior olivary nucleus. (PMID:17928434)
• A critical and selective role of p/CAF in PTF1-dependent gene activation during acinar differentiation. (PMID:18834332)
• Here we report a new case of cerebellar agenesis and neonatal diabetes mellitus whose parents are PTF1A mutation carriers. (PMID:19650412)
• Two separable genomic regions code for initiation and positive feedback of Ptf1a transgene expression in the developing nervous system. (PMID:19741120)
• ptf1a functions as a “pancreatic determiner”. (PMID:20668890)
• ICAT is a novel Ptf1a interactor that regulates pancreatic acinar differentiation and displays altered expression. (PMID:23339455)
• Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis. (PMID:24212882)
• ata indicate that E3 ubiquitin ligase thyroid hormone receptor-interacting protein 12 (TRIP12) promotes proteasomal degradation of pancreas transcription factor 1a (PTF1a)and regulates PTF1a activities. (PMID:25355311)
• The results of the present study do not support the hypothesis that high penetrant mutations in these regions of PTF1A are involved in the development of human VATER/VACTERL association or NTDs (PMID:25775927)
• Loss of Ptf1a alone is sufficient to induce acinar-to-ductal metaplasia, potentiate inflammation, and induce a KRAS-permissive, pancreatic ductal adenocarcinoma-like gene expression profile. (PMID:26151762)
• PTF1A enhancer mutations have been shown to cause neonatal diabetes associated with pancreatic agenesis (PMID:26184423)
• The results of this study suggested Ptf1a-dependent cell-fate misspecification as a novel mechanism of human brainstem pathology. (PMID:26937009)
• Data show isolated Pancreatic Aplasia Due to a Hypomorphic PTF1A Mutation (PMID:27284104)
• Study describes the wide range of gene control by PTF1A that maintains the specific characteristics of pancreatic acinar cell identity and differentiation. PTF1A controls the pancreatic acinar transcription program by direct action at a thousand genes and in collaboration with other less cell type-restricted factors to ensure acinar cell homeostasis and to suppress other cell-type-specific programs. (PMID:27697859)
• non-neural progenitor transcription factor Ptf1a alone is sufficient to directly reprogram mouse and human fibroblasts into self-renewable induced neural stem cells capable of differentiating into functional neurons, astrocytes and oligodendrocytes, and improving cognitive dysfunction of Alzheimer’s disease mouse models when transplanted (PMID:30030434)
• Clinical Characteristics and Long-term Follow-up of Patients with Diabetes Due To PTF1A Enhancer Mutations. (PMID:32893856)
• Clinical Characteristics, Molecular Features, and Long-Term Follow-Up of 15 Patients with Neonatal Diabetes: A Single-Centre Experience. (PMID:33498041)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptf1a	ENSDARG00000014479
mus_musculus	Ptf1a	ENSMUSG00000026735
rattus_norvegicus	Ptf1a	ENSRNOG00000016902
drosophila_melanogaster	Fer1	FBGN0037475

Paralogs (13): HAND1 (ENSG00000113196), TCF21 (ENSG00000118526), TWIST1 (ENSG00000122691), TCF15 (ENSG00000125878), FERD3L (ENSG00000146618), TCF23 (ENSG00000163792), HAND2 (ENSG00000164107), MSC (ENSG00000178860), FIGLA (ENSG00000183733), BHLHA9 (ENSG00000205899), TWIST2 (ENSG00000233608), SCX (ENSG00000260428), TCF24 (ENSG00000261787)

Protein

Protein identifiers

Pancreas transcription factor 1 subunit alpha — Q7RTS3 (reviewed: Q7RTS3)

Alternative names: Class A basic helix-loop-helix protein 29, Pancreas-specific transcription factor 1a, bHLH transcription factor p48, p48 DNA-binding subunit of transcription factor PTF1

All UniProt accessions (6): A0A1W2PPH2, A0A1W2PQC4, A0A1W2PQF5, A0A1W2PR29, A0A1W2PRT5, Q7RTS3

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Component of the pancreas transcription factor 1 complex (PTF1) which is composed of TCF3/p75, TCF12/p64 and PTF1A/p48. TCF3 is responsible for the nuclear import of the p48/p64 complex. Interacts with TCF3 and RBPSUH/RBP-Jkappa.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Pancreas-specific (at protein level). Loss of expression is seen in ductal type pancreas cancers.

Disease relevance. Pancreatic and cerebellar agenesis (PACA) [MIM:609069] A disease characterized by neonatal diabetes mellitus, cerebellar agenesis or hypoplasia, severe intrauterine growth retardation, the presence of very little subcutaneous fat, and dysmorphic facial features. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants 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.

Miscellaneous. An excellent marker of acinar cell differentiation in the pancreas.

RefSeq proteins (1): NP_835455* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR050283	E-box_TF_Regulators	Family

Pfam: PF00010

UniProt features (5 total): region of interest 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTS3-F1	61.81	0.19

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-210747	Regulation of gene expression in early pancreatic precursor cells
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells

MSigDB gene sets: 200 (showing top): AHRARNT_01, GOBP_HINDBRAIN_DEVELOPMENT, YAATNRNNNYNATT_UNKNOWN, GOBP_METENCEPHALON_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEUROGENESIS, GOBP_NEURAL_RETINA_DEVELOPMENT, GOBP_PANCREAS_DEVELOPMENT, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, NKX62_Q2, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, FOXJ2_01, GOBP_EXOCRINE_SYSTEM_DEVELOPMENT

GO Biological Process (22): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), tissue development (GO:0009888), retina layer formation (GO:0010842), cerebellum development (GO:0021549), pancreas development (GO:0031016), exocrine pancreas development (GO:0031017), developmental process (GO:0032502), amacrine cell differentiation (GO:0035881), retinoic acid receptor signaling pathway (GO:0048384), neuron fate commitment (GO:0048663), regulation of neural retina development (GO:0061074), nervous system development (GO:0007399), central nervous system neuron differentiation (GO:0021953), cell differentiation (GO:0030154), hindbrain development (GO:0030902), cell fate commitment (GO:0045165), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), generation of neurons (GO:0048699), retina morphogenesis in camera-type eye (GO:0060042)

GO Molecular Function (10): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), chromatin binding (GO:0003682), protein dimerization activity (GO:0046983), E-box binding (GO:0070888), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Regulation of beta-cell development	1
Developmental Cell Lineages of the Exocrine Pancreas	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
anatomical structure development	3
neural retina development	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
neuron differentiation	2
cellular developmental process	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
anatomical structure formation involved in morphogenesis	1
retina morphogenesis in camera-type eye	1
metencephalon development	1
animal organ development	1
pancreas development	1
exocrine system development	1
gland development	1
digestive system development	1
biological_process	1
central nervous system neuron differentiation	1
hormone-mediated signaling pathway	1
nuclear receptor-mediated signaling pathway	1
cell fate commitment	1
regulation of developmental process	1
system development	1
central nervous system development	1
brain development	1
cell differentiation	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
transcription cis-regulatory region binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
binding	1

Protein interactions and networks

STRING

1194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTF1A	RBPJL	Q9UBG7	992
PTF1A	RBPJ	Q06330	983
PTF1A	PDX1	P52945	851
PTF1A	HNF1A	P20823	801
PTF1A	NKX6-1	P78426	795
PTF1A	NKX6-2	Q9C056	755
PTF1A	GATA6	P78327	740
PTF1A	INS	P01308	736
PTF1A	FOXN4	Q96NZ1	734
PTF1A	NR5A2	O00482	728
PTF1A	RFX6	Q8HWS3	724
PTF1A	CPA1	P15085	719
PTF1A	GCG	P01275	716
PTF1A	HES1	Q14469	715
PTF1A	KCNJ11	Q14654	709

IntAct

0 interactions, top by confidence:

BioGRID (19): PTF1A (Affinity Capture-Western), PTF1A (Affinity Capture-Western), PTF1A (Biochemical Activity), RBPJL (Affinity Capture-Western), TCF3 (Affinity Capture-Western), RPGRIP1 (Two-hybrid), CCNDBP1 (Two-hybrid), TRIP12 (Two-hybrid), ZW10 (Two-hybrid), SPATA7 (Two-hybrid), RBPJ (Two-hybrid), AAMP (Two-hybrid), CCDC27 (Two-hybrid), TCF4 (Two-hybrid), TRIP12 (Affinity Capture-Western)

ESM2 similar proteins: A0A1W2PRP0, A6NCS4, A7Y7W2, O14512, O43638, O57601, O70220, O96004, P07812, P09023, P10085, P10284, P17483, P22091, P24899, P50548, P52954, P52955, P55318, P57100, P63156, P63157, P70447, P79772, P97832, Q02346, Q05917, Q0VCE2, Q12952, Q1XID0, Q28555, Q3I5G5, Q3Y598, Q60688, Q61660, Q63244, Q63250, Q64279, Q64305, Q64731

Diamond homologs: A8E5T6, B6VQA1, O13125, O13126, O16867, O35437, O42202, O42606, O43680, O57598, O60682, O73615, O73823, O88940, O93507, O96004, O96642, P13903, P17542, P22091, P24899, P26687, P46581, P48985, P48987, P57100, P57101, P57102, P59101, P61295, P61296, P70661, P79765, P79782, P97831, P97832, Q02575, Q02576, Q02577, Q0VCE2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FOXN4	“up-regulates quantity by expression”	PTF1A	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

170 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	84
Likely benign	53
Benign	14

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
2576993	NM_178161.3(PTF1A):c.784+1G>A	Pathogenic
265703	NM_178161.3(PTF1A):c.705del (p.Pro236fs)	Pathogenic
30651	NM_178161.3(PTF1A):c.437_460del (p.Ala146_Arg154delinsGly)	Pathogenic
3425	NM_178161.3(PTF1A):c.886C>T (p.Arg296Ter)	Pathogenic
3426	NM_178161.3(PTF1A):c.705dup (p.Pro236fs)	Pathogenic
1338531	NM_178161.3(PTF1A):c.532del (p.Ser178fs)	Likely pathogenic

SpliceAI

302 predictions. Top by Δscore:

Variant	Effect	Δscore
10:23193312:CCC:C	donor_gain	1.0000
10:23193315:G:GG	donor_gain	1.0000
10:23193310:CACCC:C	donor_gain	0.9900
10:23193313:CC:C	donor_gain	0.9900
10:23193314:CGTA:C	donor_loss	0.9900
10:23193315:G:A	donor_loss	0.9900
10:23193316:T:A	donor_loss	0.9900
10:23193317:AA:A	donor_loss	0.9900
10:23193311:ACCC:A	donor_gain	0.9800
10:23193702:AG:A	acceptor_gain	0.9800
10:23193703:GG:G	acceptor_gain	0.9800
10:23193701:CA:C	acceptor_loss	0.9700
10:23193702:A:AC	acceptor_loss	0.9700
10:23193215:G:GA	donor_gain	0.9600
10:23193341:G:GT	donor_gain	0.9500
10:23193694:A:AG	acceptor_gain	0.9500
10:23193694:ACCT:A	acceptor_gain	0.9500
10:23193695:C:G	acceptor_gain	0.9500
10:23193702:A:AG	acceptor_gain	0.9500
10:23193703:G:GG	acceptor_gain	0.9500
10:23193214:T:TA	donor_gain	0.9400
10:23193697:T:A	acceptor_gain	0.9400
10:23193703:GGGT:G	acceptor_gain	0.9400
10:23193191:G:GT	donor_gain	0.9300
10:23193293:A:AG	donor_gain	0.9300
10:23193319:G:C	donor_loss	0.9100
10:23193292:C:A	donor_gain	0.8900
10:23193318:AGTG:A	donor_loss	0.8900
10:23193747:A:AG	acceptor_gain	0.8800
10:23193748:G:GG	acceptor_gain	0.8800

AlphaMissense

2088 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:23193044:G:A	E172K	1.000
10:23193045:A:T	E172V	1.000
10:23193046:G:C	E172D	1.000
10:23193046:G:T	E172D	1.000
10:23193053:C:A	R175S	1.000
10:23193054:G:C	R175P	1.000
10:23193057:T:A	M176K	1.000
10:23193057:T:G	M176R	1.000
10:23193062:T:C	S178P	1.000
10:23193066:T:A	I179N	1.000
10:23193066:T:C	I179T	1.000
10:23193066:T:G	I179S	1.000
10:23193068:A:G	N180D	1.000
10:23193069:A:T	N180I	1.000
10:23193070:C:A	N180K	1.000
10:23193070:C:G	N180K	1.000
10:23193074:G:C	A182P	1.000
10:23193077:T:A	F183I	1.000
10:23193077:T:C	F183L	1.000
10:23193078:T:C	F183S	1.000
10:23193078:T:G	F183C	1.000
10:23193079:C:A	F183L	1.000
10:23193079:C:G	F183L	1.000
10:23193087:T:A	L186Q	1.000
10:23193087:T:C	L186P	1.000
10:23193099:T:A	I190N	1.000
10:23193099:T:C	I190T	1.000
10:23193099:T:G	I190S	1.000
10:23193101:C:A	P191T	1.000
10:23193101:C:T	P191S	1.000

dbSNP variants (sampled 300 via entrez): RS1000749035 (10:23190878 T>G), RS1000896347 (10:23191610 G>A,C), RS1002472511 (10:23194440 C>T), RS1002829550 (10:23192108 G>C), RS1003648974 (10:23192134 C>A,G), RS1003984824 (10:23191988 G>A,T), RS1004039787 (10:23192012 A>C,T), RS1004332900 (10:23191900 G>C), RS1004359328 (10:23194739 A>G), RS1004930351 (10:23190586 C>A), RS1005454489 (10:23190834 C>A,G,T), RS1005536959 (10:23192339 G>A), RS1005877534 (10:23191516 T>C), RS1006390890 (10:23191234 T>G), RS1007644848 (10:23191551 G>A)

Disease associations

OMIM: gene MIM:607194 | disease phenotypes: MIM:609069, MIM:615935, MIM:600089, MIM:606176, MIM:125850, MIM:606391, MIM:125853, MIM:615953

GenCC curated gene-disease

Disease	Classification	Inheritance
permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome	Definitive	Autosomal recessive
pancreatic agenesis 2	Definitive	Autosomal recessive
permanent neonatal diabetes mellitus	Strong	Autosomal recessive
pancreatic agenesis	Supportive	Autosomal recessive

Mondo (9): permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome (MONDO:0012192), pancreatic agenesis 2 (MONDO:0014406), monogenic diabetes (MONDO:0015967), pancreatic beta cell agenesis with neonatal diabetes mellitus (MONDO:0010813), permanent neonatal diabetes mellitus (MONDO:0100164), maturity-onset diabetes of the young (MONDO:0018911), type 2 diabetes mellitus (MONDO:0005148), kallikrein, decreased urinary activity of (MONDO:0014415), pancreatic agenesis (MONDO:0009832)

Orphanet (6): Rare genetic diabetes mellitus (Orphanet:183625), Partial pancreatic agenesis (Orphanet:2805), Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome (Orphanet:65288), Isolated permanent neonatal diabetes mellitus (Orphanet:99885), MODY (Orphanet:552), OBSOLETE: Pancreatic beta cell agenesis with neonatal diabetes mellitus (Orphanet:28455)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000325	Triangular face
HP:0000331	Short chin
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000444	Convex nasal ridge
HP:0000609	Optic nerve hypoplasia
HP:0000768	Pectus carinatum
HP:0000819	Diabetes mellitus
HP:0000857	Neonatal insulin-dependent diabetes mellitus
HP:0001250	Seizure
HP:0001265	Hyporeflexia
HP:0001321	Cerebellar hypoplasia
HP:0001371	Flexion contracture
HP:0001387	Joint stiffness
HP:0001508	Failure to thrive
HP:0001518	Small for gestational age
HP:0001522	Death in infancy
HP:0001684	Secundum atrial septal defect
HP:0001738	Exocrine pancreatic insufficiency
HP:0001903	Anemia
HP:0001943	Hypoglycemia
HP:0002104	Apnea
HP:0002335	Agenesis of cerebellar vermis
HP:0002570	Steatorrhea
HP:0002594	Pancreatic hypoplasia
HP:0003074	Hyperglycemia
HP:0003593	Infantile onset
HP:0003621	Juvenile onset

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010118_180	Type 2 diabetes	2.000000e-08

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
C563425	Diabetes Mellitus, Permanent Neonatal (supp.)
C563796	Diabetes Mellitus, Permanent Neonatal, with Cerebellar Agenesis (supp.)
C563653	Kallikrein, Decreased Urinary Activity of (supp.)
C562772	Mason-Type Diabetes (supp.)
C564908	Pancreatic Agenesis, Congenital (supp.)
C538111	Pancreatic beta cell agenesis with neonatal diabetes mellitus (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	increases methylation	1
sodium arsenite	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Folic Acid	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5R7	SEES3-1V human PTF1A, clone1	Embryonic stem cell	Male
CVCL_A5R8	SEES3-1V human PTF1A, clone2	Embryonic stem cell	Male
CVCL_A5R9	SEES3-1V human PTF1A, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02624817	PHASE4	COMPLETED	Long-Term Sulfonylurea Response in KCNJ11 Neonatal Diabetes
NCT02624830	PHASE4	UNKNOWN	Long-Term Sulfonylurea Response in ABCC8 Neonatal Diabetes (SuResponsSUR)
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
NCT00192803	PHASE4	UNKNOWN	Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs
NCT00202033	PHASE4	COMPLETED	Impact of Self-Monitoring Blood Glucose Frequency on Glycemic Control in Patients With Type 2 Diabetes
NCT00205660	PHASE4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00212290	PHASE4	COMPLETED	Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
NCT00212303	PHASE4	COMPLETED	Exercise Training in Type 2 Diabetes and Hypertension
NCT00225342	PHASE4	WITHDRAWN	Study Protocol for Rosiglitazone Versus Gliclazide in Diabetics With Angina
NCT00238472	PHASE4	COMPLETED	A Pilot Study to Evaluate the Effects of Nateglinide vs. Glibenclamide on Renal Hemodynamics and Albumin Excretion
NCT00239538	PHASE4	COMPLETED	SMOOTH - Blood Pressure Control in Diabetic/Obese Patients
NCT00240253	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Safety of Adding Symlin® to Lantus® (Insulin Glargine) in Subjects With Type 2 Diabetes