PPY

Summary

PPY (pancreatic polypeptide, HGNC:9327) is a protein-coding gene on chromosome 17q21.31, encoding Pancreatic polypeptide prohormone (P01298). Hormone secreted by pancreatic cells that acts as a regulator of pancreatic and gastrointestinal functions probably by signaling through the G protein-coupled receptor NPY4R2. It is a selective cancer dependency (DepMap: 15.5% of cell lines).

This gene encodes a member of the neuropeptide Y (NPY) family of peptides. The encoded 95 aa preproprotein is synthesized in the pancreatic islets of Langerhans and proteolytically processed to generate two peptide products. These products include the active pancreatic hormone of 36 aa and an icosapeptide of unknown function. This hormone acts as a regulator of pancreatic and gastrointestinal functions and may be important in the regulation of food intake. Plasma level of this hormone has been shown to be reduced in conditions associated with increased food intake and elevated in anorexia nervosa. In addition, infusion of this hormone in obese rodents has shown to decrease weight gain. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 5539 — RefSeq curated summary.

At a glance

• Gene–disease (curated): purine nucleoside phosphorylase deficiency (Definitive, ClinGen)
• GWAS associations: 9
• Clinical variants (ClinVar): 322 total — 20 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 1
• Cancer dependency (DepMap): dependent in 15.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_002722

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9327
Approved symbol	PPY
Name	pancreatic polypeptide
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	PNP
Ensembl gene	ENSG00000108849
Ensembl biotype	protein_coding
OMIM	167780
Entrez	5539

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000225992, ENST00000587006, ENST00000587070, ENST00000587926, ENST00000591228, ENST00000591703, ENST00000918461

RefSeq mRNA: 2 — MANE Select: NM_002722 NM_001319209, NM_002722

CCDS: CCDS11472

Canonical transcript exons

ENST00000225992 — 4 exons

Exon	Start	End
ENSE00000731194	43941143	43941214
ENSE00002797173	43942421	43942476
ENSE00003755484	43941464	43941654
ENSE00003900915	43940804	43940952

Expression profiles

Bgee: expression breadth broad, 85 present calls, max score 99.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.4041 / max 1572.7319, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166289	2.4041	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	99.82	gold quality
islet of Langerhans	UBERON:0000006	98.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.13	gold quality
pancreas	UBERON:0001264	91.22	gold quality
body of pancreas	UBERON:0001150	89.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.77	silver quality
rectum	UBERON:0001052	76.87	gold quality
oocyte	CL:0000023	73.22	gold quality
secondary oocyte	CL:0000655	57.75	gold quality
ileal mucosa	UBERON:0000331	57.09	silver quality
decidua	UBERON:0002450	56.55	gold quality
epithelial cell of pancreas	CL:0000083	56.47	silver quality
cardia of stomach	UBERON:0001162	54.83	gold quality
endothelial cell	CL:0000115	54.79	gold quality
tibialis anterior	UBERON:0001385	54.35	silver quality
parotid gland	UBERON:0001831	53.32	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
deltoid	UBERON:0001476	51.36	gold quality
duodenum	UBERON:0002114	51.34	gold quality
right coronary artery	UBERON:0001625	50.92	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
quadriceps femoris	UBERON:0001377	50.31	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
metanephric glomerulus	UBERON:0004736	49.61	gold quality
thymus	UBERON:0002370	49.54	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
vastus lateralis	UBERON:0001379	49.24	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-31	yes	172377.86
E-MTAB-5061	yes	156152.74
E-ENAD-27	yes	52887.71
E-GEOD-81608	yes	52639.76
E-GEOD-83139	yes	36582.84
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NKX2-2, PAX6

miRNA regulators (miRDB)

1 targeting PPY, 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-2467-3P	98.65	67.18	1969

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 15.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 26)

• Distribution of pancreatic polypeptide and peptide YY (PMID:11825640)
• Pancreatic polypeptide in pancreatitis (PMID:11825647)
• Pancreatic polypeptide-related tumors (PMID:11825648)
• Autonomic neuropathy is associated with impaired neuropeptide Y and this peptide responses to insulin-induced hypoglycaemia in Type I diabetic patients. (PMID:12187924)
• Early postprandial insulin and PP secretory responses were higher in Pima Indians compared with those of Caucasians. (PMID:14988250)
• Pancreatic polypeptide contributes to the regulation of energy balance in humans. (PMID:15561938)
• in healthy humans the presence of fat in the small intestine suppresses ghrelin secretion, and fat-induced suppression of ghrelin and stimulation of peptide YY and pancreatic polypeptide is dependent on fat digestion (PMID:15998659)
• Inhibits gastric emptying of solid food and delays the postprandial rise in plasma glucose and insulin. Is suggested to have physiological role in pancreatic postprandial counterregulation of gastric emptying and insulin secretion. (PMID:15998783)
• human pancreatic polypeptide inhibits TFF2 secretion in a diurnal rhythm (PMID:16359755)
• Age and sex may modulate the association between plasma PP level and the intra-abdominal fat area, suggesting that they may be determinants of parasympathetic activity. (PMID:17171555)
• Women with bulimia nervosa have significantly lower fasting and postprandial serum concentrations of pancreatic polypeptide (and GLP-1) than control subjects. (PMID:21813805)
• Self-association of PPY with phospholipid micelles addressed the delivery issues of the peptide for diabetes treatment. (PMID:22399387)
• Data suggest that beta-cell function improves in overweight subjects with type 2 diabetes who lose weight by dieting; this change is associated with a decrease in PPY secretion (i.e., plasma PPY is decreased). (PMID:22673566)
• These findings underscore the important role of the NPY-Y receptor system at several levels of the gut-brain axis in which NPY, peptide yy and pancreatic polypeptide operate both as neural and endocrine messengers–{REVIEW} (PMID:22979996)
• Pancreatic polypeptide (and peptide tyrosine-tyrosine) increases in obese woman on caloric restriction following high protein liquid meals compared to high carbohydrate liquid meals. (PMID:23371976)
• The diagnostic accuracy of the tumor markers CgA, PP, and glucagon for pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 is low. (PMID:23956349)
• Pancreatic polypeptide is recognized by two hydrophobic domains of the human Y4 receptor binding pocket. (PMID:24375409)
• These data demonstrate glucose-regulated secretion of PP and its effects on glucagon release through PPYR1 receptors expressed by alpha-cells. (PMID:25445712)
• The most important parameter in diagnosis of HG [Hyperemesis gravidarum ]was plasma PP level (PMID:25990478)
• Immunohistochemical distribution of this peptide in the epidermal skin (from abdomen, breast and face) of healthy women was analysed. (PMID:26002416)
• Because of its properties, the PP appears to be a useful marker of the endocrine insufficiency of the pancreas and a specific prognostic parameter of developing diabetes due to chronic pancreatitis (PMID:26766123)
• Peptide YY and PP are associated with circulating innate pro-inflammatory cytokines in patients after acute pancreatitis and cumulatively contribute to nearly half of the variance of IL-6, MCP-1, and TNFalpha. Future research is warranted to investigate the signaling pathways that underlie these associations. (PMID:27918953)
• GIP and pancreatic polypeptide plasma concentrations are lower in pancreatic cancer irrespective of the degree of glucose intolerance as compared to Type 2 diabetic patients and healthy controls. (PMID:28027898)
• Fasting human pancreatic polypeptide (HPP) levels are similar in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) and controls regardless of glycemic status. (PMID:29771765)
• Urinary Dopamine Excretion Rate Decreases during Acute Dietary Protein Deprivation and Is Associated with Increased Plasma Pancreatic Polypeptide Concentration. (PMID:33918032)
• Pancreatic Ppy-expressing gamma-cells display mixed phenotypic traits and the adaptive plasticity to engage insulin production. (PMID:34294685)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ppy	ENSMUSG00000017316
rattus_norvegicus	Ppy	ENSRNOG00000020874

Paralogs (2): NPY (ENSG00000122585), PYY (ENSG00000131096)

Protein

Protein identifiers

Pancreatic polypeptide prohormone — P01298 (reviewed: P01298)

Alternative names: Pancreatic polypeptide Y

All UniProt accessions (4): P01298, A0A0U1RRD5, K7EKP2, K7EML0

UniProt curated annotations — full annotation on UniProt →

Function. Hormone secreted by pancreatic cells that acts as a regulator of pancreatic and gastrointestinal functions probably by signaling through the G protein-coupled receptor NPY4R2.

Subcellular location. Secreted.

Induction. Released in circulation upon food intake. Also up-regulated by exercise.

Similarity. Belongs to the NPY family.

Isoforms (2)

UniProt ID	Names	Canonical?
P01298-1	1	yes
P01298-2	2

RefSeq proteins (2): NP_001306138, NP_002713* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001955	Pancreatic_hormone-like	Family
IPR020392	Pancreatic_hormone-like_CS	Conserved_site

Pfam: PF00159

UniProt features (9 total): peptide 2, signal peptide 1, propeptide 1, modified residue 1, splice variant 1, sequence variant 1, sequence conflict 1, helix 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7X9C	ELECTRON MICROSCOPY	3
1TZ4	SOLUTION NMR
1TZ5	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01298-F1	76.46	0.36

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): 65

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 662 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_52, MODULE_92, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, REACTOME_INNATE_IMMUNE_SYSTEM, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_BEHAVIOR, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, PAL_PRMT5_TARGETS_UP, GOCC_SECRETORY_GRANULE, MODULE_151, LFA1_Q6, ENK_UV_RESPONSE_KERATINOCYTE_UP

GO Biological Process (4): neuropeptide signaling pathway (GO:0007218), feeding behavior (GO:0007631), protein secretion (GO:0009306), signal transduction (GO:0007165)

GO Molecular Function (5): G protein-coupled receptor binding (GO:0001664), hormone activity (GO:0005179), neuropeptide hormone activity (GO:0005184), neuropeptide Y receptor binding (GO:0031841), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
G protein-coupled receptor signaling pathway	1
behavior	1
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signaling receptor binding	1
receptor ligand activity	1
hormone activity	1
neuropeptide activity	1
neuropeptide receptor binding	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2091 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPY	GCG	P01275	970
PPY	SST	P01166	955
PPY	GAST	P01350	946
PPY	INS	P01308	940
PPY	GHRL	Q9UBU3	903
PPY	NPY2R	P49146	878
PPY	SCT	P09683	855
PPY	MLN	P12872	854
PPY	VIP	P01282	844
PPY	NEUROG3	Q9Y4Z2	831
PPY	GRP	P07491	805
PPY	CCK	P06307	797
PPY	IAPP	P10997	787
PPY	GIP	P09681	778
PPY	NTS	P30990	766

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CYSRT1	PPY	psi-mi:“MI:0915”(physical association)	0.560
PPY	DPY19L3	psi-mi:“MI:0914”(association)	0.350
PPY	PRKCA	psi-mi:“MI:0914”(association)	0.350
TYMSOS	PPY	psi-mi:“MI:0914”(association)	0.350
PPY	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): CYSRT1 (Two-hybrid), DPY19L3 (Affinity Capture-MS), GPIHBP1 (Affinity Capture-MS), GNG10 (Affinity Capture-MS), MSLN (Affinity Capture-MS), PPY (Affinity Capture-MS), RHOA (Affinity Capture-MS), PRKCA (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0F7YZQ7, B3IUE0, D3Z752, E2E4L2, F1QQI2, I7C2V3, M0R8L2, P01146, P01261, P01298, P01299, P01301, P01303, P01304, P06303, P06518, P07480, P07808, P08435, P09859, P0DP55, P0DQY8, P0DQY9, P10082, P10601, P10631, P14765, P28672, P28673, P33689, P48097, P51694, P57774, Q0VC44, Q27441, Q6RUW3, Q75UG5, Q8WRC7, Q90WF4, Q9DGK7

Diamond homologs: E2E4L2, P01298, P01299, P01300, P01301, P01302, P01303, P01304, P06303, P06884, P07808, P09475, P09641, P0DP55, P10082, P10601, P10631, P11967, P13083, P14765, P15427, P18107, P28672, P28673, P28674, P29071, P29203, P29204, P29205, P29206, P31229, P33684, P33689, P37999, P39659, P41335, P41336, P41337, P41519, P48097

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PPY	up-regulates	NPY4R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	11
Uncertain significance	130
Likely benign	106
Benign	29

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071551	NM_000270.4(PNP):c.171_172delinsTT (p.Arg58Ter)	Pathogenic
1074418	NM_000270.4(PNP):c.547dup (p.Glu183fs)	Pathogenic
1076064	NM_000270.4(PNP):c.244C>T (p.Gln82Ter)	Pathogenic
1344922	NM_000270.4(PNP):c.199C>T (p.Arg67Ter)	Pathogenic
13988	NM_000270.4(PNP):c.265G>A (p.Glu89Lys)	Pathogenic
13994	NM_000270.4(PNP):c.731del (p.Lys244fs)	Pathogenic
13995	NM_000270.4(PNP):c.70C>T (p.Arg24Ter)	Pathogenic
13996	NM_000270.4(PNP):c.172C>T (p.Arg58Ter)	Pathogenic
13997	NM_000270.4(PNP):c.285+1G>A	Pathogenic
1458553	NM_000270.4(PNP):c.700C>T (p.Arg234Ter)	Pathogenic
2163413	NM_000270.4(PNP):c.406dup (p.Ile136fs)	Pathogenic
2736067	NM_000270.4(PNP):c.569G>T (p.Gly190Val)	Pathogenic
2844130	NM_000270.4(PNP):c.632_644dup (p.Asp215fs)	Pathogenic
3023072	NM_000270.4(PNP):c.513del (p.Arg171fs)	Pathogenic
4710887	NM_000270.4(PNP):c.694G>T (p.Gly232Ter)	Pathogenic
4712212	NM_000270.4(PNP):c.397del (p.Arg133fs)	Pathogenic
4717066	NM_000270.4(PNP):c.519_522dup (p.Leu175fs)	Pathogenic
4731735	NM_000270.4(PNP):c.472del (p.Arg158fs)	Pathogenic
4731810	NM_000270.4(PNP):c.281G>A (p.Trp94Ter)	Pathogenic
845655	NM_000270.4(PNP):c.751del (p.Ser251fs)	Pathogenic
13989	NM_000270.4(PNP):c.520G>C (p.Ala174Pro)	Likely pathogenic
2137547	NM_000270.4(PNP):c.387_389del (p.Ile129del)	Likely pathogenic
2178845	NM_000270.4(PNP):c.182-2A>G	Likely pathogenic
2443221	NM_000270.4(PNP):c.331del (p.Leu111fs)	Likely pathogenic
2862345	NM_000270.4(PNP):c.11+2T>A	Likely pathogenic
3064932	NM_000270.4(PNP):c.83C>T (p.Ala28Val)	Likely pathogenic
3340502	NM_000270.4(PNP):c.41_44dup (p.Glu15fs)	Likely pathogenic
3576484	NM_000270.4(PNP):c.150_151delinsAA (p.Tyr50_Gly51delinsTer)	Likely pathogenic
4077435	NM_000270.4(PNP):c.349G>A (p.Ala117Thr)	Likely pathogenic
636526	NM_000270.4(PNP):c.547G>T (p.Glu183Ter)	Likely pathogenic

SpliceAI

454 predictions. Top by Δscore:

Variant	Effect	Δscore
17:43941138:CTCA:C	donor_loss	1.0000
17:43941139:TCA:T	donor_loss	1.0000
17:43941140:CA:C	donor_loss	1.0000
17:43941141:ACCTG:A	donor_loss	1.0000
17:43941142:C:A	donor_loss	1.0000
17:43941466:AGG:A	donor_gain	1.0000
17:43941141:A:AC	donor_gain	0.9900
17:43941142:C:CC	donor_gain	0.9900
17:43941214:CCTGG:C	acceptor_loss	0.9900
17:43941215:C:CA	acceptor_loss	0.9900
17:43941216:T:A	acceptor_loss	0.9900
17:43941459:CACA:C	donor_loss	0.9900
17:43941460:ACACC:A	donor_loss	0.9900
17:43941461:CACCT:C	donor_loss	0.9900
17:43941463:C:T	donor_loss	0.9900
17:43941510:A:AC	donor_gain	0.9900
17:43941511:C:CC	donor_gain	0.9900
17:43940948:GCTCC:G	acceptor_gain	0.9800
17:43940949:CTCC:C	acceptor_gain	0.9800
17:43940949:CTCCC:C	acceptor_gain	0.9800
17:43940950:TCCC:T	acceptor_loss	0.9800
17:43940950:TCCCT:T	acceptor_gain	0.9800
17:43940951:CC:C	acceptor_gain	0.9800
17:43940952:CC:C	acceptor_gain	0.9800
17:43940953:C:CC	acceptor_gain	0.9800
17:43941651:CCAT:C	acceptor_gain	0.9800
17:43941652:CATC:C	acceptor_gain	0.9800
17:43941653:ATCTG:A	acceptor_loss	0.9800
17:43941654:TC:T	acceptor_loss	0.9800
17:43941655:C:CA	acceptor_loss	0.9800

AlphaMissense

593 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:43941509:T:C	Y49C	0.966
17:43941497:A:G	L53P	0.961
17:43941464:C:A	R64M	0.956
17:43941473:G:A	T61I	0.955
17:43941509:T:G	Y49S	0.955
17:43941510:A:G	Y49H	0.949
17:43941554:G:T	P34Q	0.940
17:43941485:A:C	I57S	0.937
17:43941555:G:A	P34S	0.936
17:43941469:C:A	R62S	0.932
17:43941469:C:G	R62S	0.932
17:43941485:A:G	I57T	0.932
17:43941481:G:C	N58K	0.930
17:43941481:G:T	N58K	0.930
17:43941214:C:A	R64S	0.928
17:43941214:C:G	R64S	0.928
17:43941516:C:G	A47P	0.925
17:43941485:A:T	I57N	0.924
17:43941494:C:G	R54P	0.924
17:43941497:A:T	L53H	0.923
17:43941464:C:G	R64T	0.922
17:43941476:A:G	L60P	0.918
17:43941510:A:C	Y49D	0.918
17:43941546:G:A	P37S	0.914
17:43941473:G:T	T61N	0.912
17:43941545:G:T	P37Q	0.909
17:43941510:A:T	Y49N	0.905
17:43941482:T:A	N58I	0.901
17:43941554:G:C	P34R	0.901
17:43941488:T:C	Y56C	0.900

dbSNP variants (sampled 300 via entrez): RS1000226721 (17:43941958 T>C), RS1000763173 (17:43944637 C>T), RS1001390265 (17:43941077 T>C), RS1002123102 (17:43943058 C>T), RS1002305659 (17:43943392 G>A,T), RS1002405175 (17:43945634 G>A), RS1003062221 (17:43942243 G>A), RS1004186624 (17:43944169 C>T), RS1004961655 (17:43940646 G>A,C), RS1004991279 (17:43941041 C>T), RS1005978922 (17:43945598 C>T), RS1007087529 (17:43942317 A>G), RS1007750125 (17:43945026 G>C), RS1008121049 (17:43941812 C>T), RS1008715255 (17:43943799 G>A)

Disease associations

OMIM: gene MIM:167780 | disease phenotypes: MIM:613179

GenCC curated gene-disease

Disease	Classification	Inheritance
purine nucleoside phosphorylase deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
purine nucleoside phosphorylase deficiency	Definitive	AR

Mondo (2): purine nucleoside phosphorylase deficiency (MONDO:0013171), severe combined immunodeficiency (MONDO:0015974)

Orphanet (2): Purine nucleoside phosphorylase deficiency (Orphanet:760), Severe combined immunodeficiency (Orphanet:183660)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0004430	Severe combined immunodeficiency

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002666_3	Interferon alpha levels in systemic lupus erythematosus	1.000000e-07
GCST004029_5	Angiotensin-converting enzyme inhibitor intolerance	2.000000e-06
GCST005312_33	Menopause (age at onset)	2.000000e-10
GCST006585_2441	Blood protein levels	1.000000e-29
GCST010242_182	HDL cholesterol levels	4.000000e-08
GCST90011898_21	Alanine aminotransferase levels	2.000000e-08
GCST90011899_137	Aspartate aminotransferase levels	1.000000e-11
GCST90013663_10	Alanine aminotransferase levels	3.000000e-08
GCST90013664_36	Aspartate aminotransferase levels	1.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006517	interferon alpha measurement
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0004704	age at menopause
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750
C562587	Purine Nucleoside Phosphorylase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases expression	1
sodium arsenite	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Orlistat	decreases reaction, increases secretion	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	increases expression, affects cotreatment	1
Dactinomycin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Triglycerides	decreases reaction, increases secretion	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	PHASE3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	PHASE2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	PHASE2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	PHASE2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
NCT00008450	PHASE1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT00028236	PHASE1	COMPLETED	Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
NCT00152100	PHASE1	COMPLETED	Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT02860559	PHASE1	UNKNOWN	Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00228852	PHASE1/PHASE2	COMPLETED	IMM 0212: Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency
NCT00579137	PHASE1/PHASE2	TERMINATED	Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
NCT01129544	PHASE1/PHASE2	COMPLETED	Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02127892	PHASE1/PHASE2	TERMINATED	SCID Bu/Flu/ATG Study With T Cell Depletion
NCT02963064	PHASE1/PHASE2	TERMINATED	JSP191 Antibody Targeting Conditioning in SCID Patients
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03538899	PHASE1/PHASE2	RECRUITING	Autologous Gene Therapy for Artemis-Deficient SCID
NCT03597594	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID)
NCT00001255	Not specified	COMPLETED	Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006335	Not specified	COMPLETED	Influences on Female Adolescents’ Decisions Regarding Testing for Carrier Status of XSCID
NCT00055172	Not specified	RECRUITING	Genetic Basis of Immunodeficiency
NCT00695279	Not specified	COMPLETED	Long Term Follow Up Of Patients Who Have Received Gene Therapy Or Gene Marked Products
NCT00845416	Not specified	COMPLETED	Newborn Screening for Severe Combined Immunodeficiency (SCID) in a High-Risk Population
NCT01186913	Not specified	ENROLLING_BY_INVITATION	Natural History Study of SCID Disorders
NCT01346150	Not specified	UNKNOWN	Patients Treated for SCID (1968-Present)
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT01953016	Not specified	COMPLETED	Participation in a Research Registry for Immune Disorders
NCT02231983	Not specified	UNKNOWN	Clinical Characteristics and Genetic Profiles of Severe Combined Immunodeficiency in China
NCT02590328	Not specified	COMPLETED	Neonatal Screening of Severe Combined Immunodeficiencies
NCT04049084	Not specified	ENROLLING_BY_INVITATION	An Observational LTFU Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for ADA-SCID
NCT04172181	Not specified	UNKNOWN	Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for SCID
NCT04246840	Not specified	COMPLETED	Study Through Imaging of Visceral Lymphoid Organs in Patients With SCID Who Have Recieved Bone Marrow Allograft