PPDPF

Summary

PPDPF (pancreatic progenitor cell differentiation and proliferation factor, HGNC:16142) is a protein-coding gene on chromosome 20q13.33, encoding Pancreatic progenitor cell differentiation and proliferation factor (Q9H3Y8). Probable regulator of exocrine pancreas development.

Predicted to be involved in cell differentiation. Predicted to act upstream of or within TORC1 signaling and liver development. Located in mitochondrion.

Source: NCBI Gene 79144 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 44 total — 3 pathogenic
• MANE Select transcript: NM_024299

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16142
Approved symbol	PPDPF
Name	pancreatic progenitor cell differentiation and proliferation factor
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	dJ697K14.9, exdpf
Ensembl gene	ENSG00000125534
Ensembl biotype	protein_coding
Entrez	79144

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000370177, ENST00000370179, ENST00000464438, ENST00000473620, ENST00000718243, ENST00000857110, ENST00000857111, ENST00000857112, ENST00000857113, ENST00000857114

RefSeq mRNA: 2 — MANE Select: NM_024299 NM_001353423, NM_024299

CCDS: CCDS13523

Canonical transcript exons

ENST00000370179 — 4 exons

Exon	Start	End
ENSE00001452008	63521512	63521589
ENSE00001452012	63520765	63520894
ENSE00001452013	63521668	63522206
ENSE00001452015	63521284	63521363

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 916.1025 / max 8735.2255, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185819	915.4926	1826
185820	0.6099	262

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.58	gold quality
right coronary artery	UBERON:0001625	99.52	gold quality
mucosa of transverse colon	UBERON:0004991	99.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.46	gold quality
skin of abdomen	UBERON:0001416	99.43	gold quality
skin of leg	UBERON:0001511	99.40	gold quality
minor salivary gland	UBERON:0001830	99.38	gold quality
popliteal artery	UBERON:0002250	99.34	gold quality
tibial artery	UBERON:0007610	99.34	gold quality
saliva-secreting gland	UBERON:0001044	99.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.33	gold quality
right uterine tube	UBERON:0001302	99.31	gold quality
coronary artery	UBERON:0001621	99.31	gold quality
left coronary artery	UBERON:0001626	99.31	gold quality
apex of heart	UBERON:0002098	99.30	gold quality
descending thoracic aorta	UBERON:0002345	99.29	gold quality
aorta	UBERON:0000947	99.26	gold quality
ectocervix	UBERON:0012249	99.25	gold quality
body of stomach	UBERON:0001161	99.24	gold quality
lower esophagus	UBERON:0013473	99.22	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.22	gold quality
endocervix	UBERON:0000458	99.21	gold quality
tibial nerve	UBERON:0001323	99.21	gold quality
ascending aorta	UBERON:0001496	99.20	gold quality
parotid gland	UBERON:0001831	99.20	silver quality
thoracic aorta	UBERON:0001515	99.19	gold quality
metanephros cortex	UBERON:0010533	99.19	gold quality
mucosa of stomach	UBERON:0001199	99.18	gold quality
adenohypophysis	UBERON:0002196	99.18	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.18	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	20981.34
E-MTAB-8495	yes	4713.88
E-MTAB-6308	yes	4136.03
E-GEOD-134144	yes	3040.95
E-MTAB-8410	yes	2513.44
E-HCAD-4	yes	104.71
E-HCAD-10	yes	22.69
E-HCAD-11	yes	22.23
E-ANND-3	yes	20.61
E-MTAB-6701	yes	19.43
E-MTAB-10553	yes	18.57
E-MTAB-8142	yes	14.12
E-HCAD-1	yes	12.94
E-MTAB-10042	yes	12.22
E-HCAD-9	yes	10.24

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PTF1A

Literature-anchored findings (GeneRIF, showing 3)

• Circ-FOXM1 upregulated the level of pancreatic progenitor cell differentiation and proliferation factor (PPDPF) and metastasis-associated in colon cancer 1 (MACC1) by sponging miR-1304-5p, thereby increasing the proliferation and invasion of non-small cell lung cancer cells. (PMID:30954221)
• Pancreatic progenitor epigenome maps prioritize type 2 diabetes risk genes with roles in development. (PMID:33544077)
• PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling. (PMID:34031390)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppdpfa	ENSDARG00000007682
danio_rerio	ppdpfb	ENSDARG00000031317
mus_musculus	Ppdpf	ENSMUSG00000016344
rattus_norvegicus	Ppdpf	ENSRNOG00000012722

Paralogs (1): PPDPFL (ENSG00000168333)

Protein

Protein identifiers

Pancreatic progenitor cell differentiation and proliferation factor — Q9H3Y8 (reviewed: Q9H3Y8)

Alternative names: Exocrine differentiation and proliferation factor

All UniProt accessions (2): Q9H3Y8, X6R7I6

UniProt curated annotations — full annotation on UniProt →

Function. Probable regulator of exocrine pancreas development.

Similarity. Belongs to the PPDPF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H3Y8-1	1	yes
Q9H3Y8-2	2

RefSeq proteins (2): NP_001340352, NP_077275* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026754	PPDPF	Family

Pfam: PF15060

UniProt features (8 total): region of interest 2, compositionally biased region 2, splice variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3Y8-F1	60.64	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 9

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 127 (showing top): GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, UEDA_PERIFERAL_CLOCK, DOANE_RESPONSE_TO_ANDROGEN_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_TOR_SIGNALING, LIU_CMYB_TARGETS_UP, MODULE_48, MODULE_207, MODULE_95, PARENT_MTOR_SIGNALING_UP, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, GAVIN_FOXP3_TARGETS_CLUSTER_T7, CHESLER_BRAIN_QTL_CIS

GO Biological Process (5): liver development (GO:0001889), cell differentiation (GO:0030154), TORC1 signaling (GO:0038202), multicellular organism development (GO:0007275), TOR signaling (GO:0031929)

GO Molecular Function (0):

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gland development	1
hepaticobiliary system development	1
cellular developmental process	1
TOR signaling	1
multicellular organismal process	1
anatomical structure development	1
intracellular signal transduction	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPDPF	MACC1	Q6ZN28	479
PPDPF	PTK6	Q13882	476
PPDPF	EEF1A2	P54266	444
PPDPF	TSACC	Q96A04	404
PPDPF	C12orf54	Q6X4T0	397
PPDPF	ARMH4	Q86TY3	393
PPDPF	FNDC11	Q9BVV2	377
PPDPF	TMEM14A	Q9Y6G1	370
PPDPF	B9D1	Q9UPM9	368
PPDPF	EPN2	O95208	353
PPDPF	RNF112	Q9ULX5	353
PPDPF	GMEB2	Q9UKD1	336
PPDPF	PPDPFL	Q8WWR9	331
PPDPF	ACKR1	Q16570	325
PPDPF	MYADML2	A6NDP7	322

IntAct

0 interactions, top by confidence:

BioGRID (23): PPDPF (Affinity Capture-Western), RPTOR (Affinity Capture-Western), DDB1 (Affinity Capture-Western), PPDPF (Affinity Capture-Western), RPTOR (Reconstituted Complex), DDB1 (Reconstituted Complex), CTSC (Two-hybrid), DNAJB1 (Two-hybrid), GLMN (Two-hybrid), PRMT1 (Two-hybrid), PLSCR1 (Two-hybrid), TRIP6 (Two-hybrid), MT2A (Two-hybrid), BRE (Two-hybrid), BRE (Affinity Capture-Western)

ESM2 similar proteins: A2AQ25, A4IGU9, A7E300, A8E4V2, B5DF41, B5DGK1, F1N4M2, O15079, O55003, O60238, O60516, Q0IHF8, Q0P5A7, Q12983, Q13541, Q14DQ1, Q1LWL8, Q3B7T9, Q3T013, Q3UN70, Q3ZCB6, Q5PR01, Q5XG16, Q5XKK7, Q5ZLN7, Q60876, Q62622, Q62739, Q63744, Q68EF0, Q68FF7, Q6AYT4, Q6PBI2, Q6PFP3, Q6ZNC4, Q7Z309, Q80U23, Q80VV3, Q8AVU0, Q8LD26

Diamond homologs: A4IGU9, B5DGK1, Q0IHF8, Q3ZCB6, Q5PR01, Q6PBI2, Q6PFP3, Q8AVU0, Q8WWR9, Q9CR37, Q9H3Y8, A8E653

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	33
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1073749	NC_000020.10:g.(?62076002)(62324646_?)del	Pathogenic
4820119	NC_000020.10:g.(62073884_62076012)_(62324636_62325671)del	Pathogenic
642634	NC_000020.11:g.(?63472148)(63528152_?)del	Pathogenic

SpliceAI

413 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63521362:GC:G	donor_gain	1.0000
20:63521364:G:GG	donor_gain	1.0000
20:63521507:TCCA:T	acceptor_loss	1.0000
20:63521508:CCAG:C	acceptor_loss	1.0000
20:63521509:CA:C	acceptor_loss	1.0000
20:63521510:A:AG	acceptor_gain	1.0000
20:63521511:G:A	acceptor_loss	1.0000
20:63521511:G:GG	acceptor_gain	1.0000
20:63521589:GGT:G	donor_loss	1.0000
20:63521590:G:A	donor_loss	1.0000
20:63521591:T:G	donor_loss	1.0000
20:63520892:CAG:C	donor_loss	0.9900
20:63520893:AG:A	donor_loss	0.9900
20:63520894:GGTGA:G	donor_loss	0.9900
20:63520895:G:A	donor_loss	0.9900
20:63521277:T:G	acceptor_gain	0.9900
20:63521359:CCGGC:C	donor_gain	0.9900
20:63521360:CGGC:C	donor_gain	0.9900
20:63521361:GGCG:G	donor_gain	0.9900
20:63521511:GGCC:G	acceptor_gain	0.9900
20:63521568:G:GT	donor_gain	0.9900
20:63521568:G:T	donor_gain	0.9900
20:63521360:CGGCG:C	donor_loss	0.9800
20:63521361:GGC:G	donor_gain	0.9800
20:63521362:GCG:G	donor_gain	0.9800
20:63521363:CGT:C	donor_loss	0.9800
20:63521364:GTGA:G	donor_loss	0.9800
20:63521365:TGA:T	donor_loss	0.9800
20:63521366:GAGTA:G	donor_loss	0.9800
20:63521367:AGT:A	donor_loss	0.9800

AlphaMissense

741 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63521319:T:C	I4T	0.973
20:63521343:C:A	A12D	0.971
20:63521699:G:C	W55C	0.970
20:63521699:G:T	W55C	0.970
20:63521354:T:C	Y16H	0.962
20:63521337:T:A	L10H	0.958
20:63521331:G:A	G8D	0.957
20:63521319:T:A	I4N	0.953
20:63521697:T:A	W55R	0.953
20:63521697:T:C	W55R	0.953
20:63521330:G:C	G8R	0.949
20:63521313:C:T	A2V	0.945
20:63521696:G:C	W54C	0.944
20:63521696:G:T	W54C	0.944
20:63521319:T:G	I4S	0.941
20:63521352:A:T	D15V	0.941
20:63521354:T:G	Y16D	0.941
20:63521514:C:A	R20S	0.935
20:63521694:T:A	W54R	0.933
20:63521694:T:C	W54R	0.933
20:63521342:G:C	A12P	0.928
20:63521361:G:C	R18P	0.927
20:63521703:A:C	S57R	0.919
20:63521705:C:A	S57R	0.919
20:63521705:C:G	S57R	0.919
20:63521709:T:C	F59L	0.917
20:63521711:T:A	F59L	0.917
20:63521711:T:G	F59L	0.917
20:63521342:G:A	A12T	0.916
20:63521313:C:A	A2E	0.914

dbSNP variants (sampled 300 via entrez): RS1000105712 (20:63519296 T>A), RS1000114418 (20:63520337 A>T), RS1000899026 (20:63520940 G>GGGGGCGA), RS1000910367 (20:63521075 G>C,T), RS1001797628 (20:63521706 T>C,G), RS1002135034 (20:63519267 G>T), RS1002230005 (20:63519004 G>A,C), RS1002533022 (20:63520836 C>G), RS1003392517 (20:63521194 A>G), RS1003468013 (20:63522095 C>G,T), RS1003807688 (20:63520060 G>A,T), RS1004202756 (20:63519795 G>A), RS1004968305 (20:63519595 C>T), RS1005887914 (20:63522667 C>G,T), RS1005965475 (20:63522066 C>G,T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:616409, MIM:121200, MIM:600513

GenCC curated gene-disease

Mondo (4): developmental and epileptic encephalopathy (MONDO:0100620), developmental and epileptic encephalopathy, 33 (MONDO:0014625), seizures, benign familial neonatal, 1 (MONDO:0007365), familial sleep-related hypermotor epilepsy (MONDO:0000030)

Orphanet (3): Non-specific early-onset epileptic encephalopathy (Orphanet:442835), Self-limited neonatal epilepsy (Orphanet:1949), Sleep-related hypermotor epilepsy (Orphanet:98784)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001942_22	Prostate cancer	4.000000e-16
GCST004521_202	Autism spectrum disorder or schizophrenia	4.000000e-08
GCST008058_112	Estimated glomerular filtration rate	2.000000e-17
GCST008103_74	Bipolar disorder	8.000000e-07
GCST008115_28	Bipolar I disorder	3.000000e-07
GCST012020_26	Serum metabolite levels	5.000000e-14
GCST012021_69	Serum metabolite levels	5.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009963	bipolar I disorder

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C579932	Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (supp.)
C567743	Epilepsy, Benign Neonatal, 1, And-Or Myokymia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	4
sodium arsenite	increases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Acetaminophen	increases expression, affects expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Smoke	decreases expression, increases abundance	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
fluorene-9-bisphenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
lead acetate	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cupric chloride	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
bisphenol S	increases methylation	1
jinfukang	increases expression	1
Atrazine	increases expression	1
Cadmium	decreases expression, increases abundance	1
Curcumin	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Hydrogen Peroxide	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT03876444	PHASE2/PHASE3	UNKNOWN	Intravenous Methylprednisolone Versus Oral Prednisolone for Infantile Spasms
NCT05279118	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT04302116	Not specified	RECRUITING	Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm
NCT05538936	Not specified	COMPLETED	The Effect of Spa and Massage on Babies on Colic Symptoms
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06266234	Not specified	RECRUITING	Characterization by Automated System on Infantile Spasmes
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07413211	Not specified	RECRUITING	Genetic Developmental and Epileptic Encephalopathy Natural History Study for Clinical Trial Readiness
NCT07531511	Not specified	NOT_YET_RECRUITING	SLC6A1-NDD Prospective Longitudinal Natural History Study
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).