NPY

Summary

NPY (neuropeptide Y, HGNC:7955) is a protein-coding gene on chromosome 7p15.3, encoding Pro-neuropeptide Y (P01303). NPY is implicated in the control of feeding and in secretion of gonadotrophin-release hormone.

This gene encodes a neuropeptide that is widely expressed in the central nervous system and influences many physiological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. The neuropeptide functions through G protein-coupled receptors to inhibit adenylyl cyclase, activate mitogen-activated protein kinase (MAPK), regulate intracellular calcium levels, and activate potassium channels. A polymorphism in this gene resulting in a change of leucine 7 to proline in the signal peptide is associated with elevated cholesterol levels, higher alcohol consumption, and may be a risk factor for various metabolic and cardiovascular diseases. The protein also exhibits antimicrobial activity against bacteria and fungi.

Source: NCBI Gene 4852 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_000905

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7955
Approved symbol	NPY
Name	neuropeptide Y
Location	7p15.3
Locus type	gene with protein product
Status	Approved
Aliases	PYY4
Ensembl gene	ENSG00000122585
Ensembl biotype	protein_coding
OMIM	162640
Entrez	4852

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000242152, ENST00000405982, ENST00000407573, ENST00000925261, ENST00000925262

RefSeq mRNA: 1 — MANE Select: NM_000905 NM_000905

CCDS: CCDS5387

Canonical transcript exons

ENST00000242152 — 4 exons

Exon	Start	End
ENSE00000831997	24285241	24285428
ENSE00000831998	24289499	24289579
ENSE00001207328	24291663	24291862
ENSE00001892137	24284190	24284275

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 97.41.

FANTOM5 (CAGE): breadth broad, TPM avg 9.8547 / max 815.5257, expressed in 332 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77691	9.5039	320
77692	0.2880	79
77693	0.0628	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	97.41	gold quality
putamen	UBERON:0001874	97.23	gold quality
caudate nucleus	UBERON:0001873	97.19	gold quality
type B pancreatic cell	CL:0000169	95.94	gold quality
nucleus accumbens	UBERON:0001882	95.72	gold quality
amygdala	UBERON:0001876	95.61	gold quality
middle frontal gyrus	UBERON:0002702	95.06	gold quality
prefrontal cortex	UBERON:0000451	94.59	gold quality
cingulate cortex	UBERON:0003027	93.36	gold quality
prostate gland	UBERON:0002367	93.28	gold quality
anterior cingulate cortex	UBERON:0009835	93.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.03	gold quality
ventricular zone	UBERON:0003053	92.47	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.96	gold quality
orbitofrontal cortex	UBERON:0004167	91.42	gold quality
telencephalon	UBERON:0001893	90.69	gold quality
frontal pole	UBERON:0002795	90.04	gold quality
neocortex	UBERON:0001950	89.89	gold quality
frontal cortex	UBERON:0001870	89.59	gold quality
temporal lobe	UBERON:0001871	89.35	gold quality
cerebral cortex	UBERON:0000956	89.27	gold quality
Brodmann (1909) area 10	UBERON:0013541	89.27	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.02	gold quality
right frontal lobe	UBERON:0002810	87.89	gold quality
forebrain	UBERON:0001890	87.47	gold quality
Ammon’s horn	UBERON:0001954	87.46	gold quality
lateral globus pallidus	UBERON:0002476	87.41	gold quality
embryo	UBERON:0000922	87.40	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	86.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.13	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9906	yes	7721.31
E-GEOD-83139	yes	1335.75
E-ANND-5	yes	462.22
E-MTAB-9388	yes	12.38
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ASCL1, BSX, CREB1, EGR1, ESR1, FOS, FOXO1, JUN, LHX1, PBX1, PTF1A, SP1, STAT3, TFAP2A

miRNA regulators (miRDB)

29 targeting NPY, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-3620-5P	97.42	63.95	792
HSA-MIR-1587	96.95	64.03	932

Literature-anchored findings (GeneRIF, showing 40)

• Aging of human microvascular endothelial cells in vitro led to a loss of their mitogenic responses to NPY accompanied by a lack of NPY receptor mRNAs (PMID:11814620)
• Circulating NPY in fulminant hepatic failure does not seem to reflect cerebral blood flow. (PMID:11884208)
• NPY regulates the CRH system of the human hypothalamus and some of the effects of NPY on metabolic, autonomic, and endocrine functions may be mediated through CRH (PMID:11932939)
• Autonomic neuropathy is associated with impaired pancreatic polypeptide and this peptide responses to insulin-induced hypoglycaemia in Type I diabetic patients. (PMID:12187924)
• a study of ligand-receptor interactions (review) (PMID:12209475)
• Neuropeptide Y Pro7 frequencies in the control populations were similar to the alcoholics, in Finns and Swedes, yielding no association with neuropeptide Y Pro7 frequency, in contrast with the Yale study. (PMID:12544000)
• NPY affects the cortical sequelae of hunger and satiety regulation as reflected by cortical DC-potentials in man. (PMID:12689610)
• Leu7Pro polymorphism of the NPY gene associates with alterations in FFA metabolism but does not have an impact on insulin sensitivity, insulin secretion, or glucose metabolism (PMID:12759898)
• hypothalamic neuropeptide Y in the phenotypic expression of hyperphagia in the fa/fa pups during the second postnatal week (PMID:12782203)
• Proline 7 substitution in signal peptide of the NPY is associated with enhanced endothelial-dependent vasodilation. (PMID:12818415)
• genetically determined changes in NPY levels lead to widespread consequences in the control of sympathoadrenal, metabolic, and hormonal balance in healthy subjects. (PMID:12843176)
• a novel polymorphism in the promoter region of the neuropeptide Y gene is associated with schizophrenia in humans. (PMID:12875921)
• Analysis of a repressor region in the neuropeptide Y gene that binds Oct-1 and Pbx-1 in neurons. (PMID:12878188)
• Leu7Pro polymorphism may contribute to the genetic susceptibility to diabetic nephropathy and coronary disease in type 1 diabetic patients (PMID:14747236)
• Proportional comparison of NPY neurons in four compartments, upper cortical layers, lower cortical layers, subcortical white matter and deep white matter, demonstrated differential distribution between schizophrenic brains and controls. (PMID:14751436)
• Aging women is have increased NPY gene expression. Functional relationship between NPY and POMC neurons demonstrated in other species also exists in human. Increase in NPY mRNA in older women may be due to factors other than ovarian failure of menopause. (PMID:15126561)
• NPY participates in sympathetically mediated cutaneous vasoconstriction in humans during whole body cooling. (PMID:15165988)
• the NPY T1128C polymorphism is an independent predictor for myocardial infarction and stroke in a Swedish hypertensive population. (PMID:15201542)
• The leucine 7/proline 7 polymorphism in the NPY signal gene may favorably affect femoral neck bone mineral density in postmenopausal women. (PMID:15336593)
• Our data support the hypothesis of epistatic interaction between ADRB2 and NPY in regulation of LDL levels in hypertensive subjects. (PMID:15364898)
• Number and size of neuropeptide Y positive cells were greater at birth and reached maximal values of 100-400 cells per 1 mm2 and 2-5 microm in diameter, respectively. (PMID:15485137)
• results corroborate the involvement of neuropeptide Y in sexual maturation and its role in delayed puberty (PMID:15625769)
• Results indicate that the neuropeptide Y signaling system is implicated in body weight regulation and suggest a new and unexpected functional role of a signal peptide. (PMID:15680469)
• choroid contains abundant NPY and TH nerve fibers related to chroroidal vascular structures (PMID:15736042)
• Kidney transplantation does not normalize plasma NPY posttransplant. Transplanted kidney with good excretory functions and immunosupressive therapy are not essential factors involved in maintence of elevated NPY plasma level early posttransplant. (PMID:15759545)
• the Leu7Pro polymorphism of preproNPY is related to decreased level of basal sympathetic activity, decreased insulin secretion, and delayed ghrelin suppression during oral glucose tolerance test (PMID:15797951)
• The T1128C polymorphism of the NPY gene is population specific and extremely low in a Chinese population. (PMID:15847953)
• human umbilical-vein endothelial cells produce, store and respond to NPY, suggesting an autocrine regulatory role for NPY in the endothelium (PMID:15850450)
• study provides the evidence that Leu7Pro polymorphism in the neuropeptide Y (NPY) gene is associated with impaired glucose tolerance (IGT) and type 2 diabetes in Swedish men (PMID:15926114)
• NPY polymorphisms might influence cholesterol metabolism, but might not act as major risk factor in Alzheimer’s disease (PMID:15959845)
• orexin A, NPY, leptin play an important role in the regulation of energy metabolism in humans; in obesity the activity of these peptides is disturbed. (PMID:16135994)
• Altered neuroregulation of the neuropeptides (leptin and NPY) secretion may contribute persistent amenorrhea after weight gain in anorectic patients with low initial body mass index (PMID:16136022)
• Y1 receptor activation by neuropeptide Y regulates the growth of prostate cancer cells (PMID:16339211)
• This review discusses the dual role of NPY as modulator of sympathetic co-transmission; it facilitates vascular smooth muscle reactivity and modulates the presynaptic release of adenosine triphosphate (ATP) and noradrenaline. (PMID:16382997)
• This review summarizes the evidence implicating peripheral and central NPY in the development and/or maintenance of hypertension or stress-induced hypertension in humans, and points out the definitive proof of the role of NPY that is still lacking. (PMID:16382999)
• This review defines NPY as an important sympathetic transmitter that clearly acts via intracerebral nerves as well to regulate local cerebral blood flow. (PMID:16383000)
• This is a review of evidence in support of a potential role for NPY in heart failure progression and remodeling via actions on vascular and cardiomyocyte function exerted via multiple NPY receptors (PMID:16383001)
• In this review, NPY is a mediator and a marker of chronic stress in humans, including extreme trauma and posttraumatic stress disorder (PMID:16383009)
• This review underscores the need to understand how the functions of NPY are altered by the chronic neurodegenerative changes that occur in Alzheimer’s, Parkinson’s, and Huntington’s disease. (PMID:16383010)
• Neuropeptide Y levels were significantly higher in normal cycling athletes, suggesting possibility of protective role of neuropeptide Y in maintenance of menstrual cycle in highly trained athletes. (PMID:16500360)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	npy	ENSDARG00000036222
mus_musculus	Npy	ENSMUSG00000029819
rattus_norvegicus	Npy	ENSRNOG00000046449

Paralogs (2): PPY (ENSG00000108849), PYY (ENSG00000131096)

Protein

Protein identifiers

Pro-neuropeptide Y — P01303 (reviewed: P01303)

All UniProt accessions (2): A4D158, P01303

UniProt curated annotations — full annotation on UniProt →

Function. NPY is implicated in the control of feeding and in secretion of gonadotrophin-release hormone.

Subcellular location. Secreted. Cytoplasmic vesicle. Secretory vesicle. Neuronal dense core vesicle.

Tissue specificity. One of the most abundant peptides in the nervous system. Also found in some chromaffin cells of the adrenal medulla.

Post-translational modifications. The neuropeptide Y form is cleaved at Pro-30 by the prolyl endopeptidase FAP (seprase) activity (in vitro).

Similarity. Belongs to the NPY family.

RefSeq proteins (1): NP_000896* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00159

UniProt features (11 total): peptide 2, modified residue 2, sequence variant 2, signal peptide 1, helix 1, site 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
7RTA	X-RAY DIFFRACTION	2.6
7YOO	ELECTRON MICROSCOPY	3.11
7VGX	ELECTRON MICROSCOPY	3.2
7X9A	ELECTRON MICROSCOPY	3.2
8K6N	ELECTRON MICROSCOPY	3.2
8K6M	ELECTRON MICROSCOPY	3.3
8K6O	ELECTRON MICROSCOPY	3.3
7X9B	ELECTRON MICROSCOPY	3.4
1QFA	SOLUTION NMR
1RON	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01303-F1	74.97	0.29

Antibody-complex structures (SAbDab): 6 — 7RTA, 7VGX, 7YOO, 8K6M, 8K6N, 8K6O

Functional residue map

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

Catalytic / active sites (1): 30–31 (cleavage; by fap)

Post-translational modifications (2): 64, 83

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events
R-HSA-9615017	FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes

MSigDB gene sets: 304 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_92, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_BEHAVIOR, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_PHOTOPERIODISM, GOCC_SECRETORY_GRANULE, GOBP_ADULT_BEHAVIOR, MODULE_64, GOBP_POSITIVE_REGULATION_OF_AMINE_METABOLIC_PROCESS

GO Biological Process (27): negative regulation of acute inflammatory response to antigenic stimulus (GO:0002865), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), neuropeptide signaling pathway (GO:0007218), chemical synaptic transmission (GO:0007268), feeding behavior (GO:0007631), positive regulation of cell population proliferation (GO:0008284), adult feeding behavior (GO:0008343), positive regulation of cell-substrate adhesion (GO:0010811), central nervous system neuron development (GO:0021954), cerebral cortex development (GO:0021987), neuron projection development (GO:0031175), positive regulation of appetite (GO:0032100), regulation of nerve growth factor production (GO:0032903), monocyte activation (GO:0042117), drinking behavior (GO:0042756), negative regulation of blood pressure (GO:0045776), positive regulation of dopamine metabolic process (GO:0045964), short-day photoperiodism (GO:0048572), developmental growth (GO:0048589), intestinal epithelial cell differentiation (GO:0060575), positive regulation of ERK1 and ERK2 cascade (GO:0070374), regulation of presynaptic cytosolic calcium ion concentration (GO:0099509), synaptic signaling via neuropeptide (GO:0099538), positive regulation of eating behavior (GO:1904000), obsolete positive regulation of nitric oxide metabolic process (GO:1904407), regulation of synaptic vesicle exocytosis (GO:2000300), regulation of blood pressure (GO:0008217)

GO Molecular Function (8): G protein-coupled receptor activity (GO:0004930), signaling receptor binding (GO:0005102), neuropeptide hormone activity (GO:0005184), calcium channel regulator activity (GO:0005246), neuropeptide Y receptor binding (GO:0031841), G protein-coupled receptor binding (GO:0001664), hormone activity (GO:0005179), protein binding (GO:0005515)

GO Cellular Component (10): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794), terminal bouton (GO:0043195), perikaryon (GO:0043204), perinuclear region of cytoplasm (GO:0048471), GABA-ergic synapse (GO:0098982), neuronal dense core vesicle (GO:0098992), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
G protein-coupled receptor signaling pathway	3
cytoplasm	3
feeding behavior	2
neuron development	2
acute inflammatory response to antigenic stimulus	1
negative regulation of acute inflammatory response	1
negative regulation of inflammatory response to antigenic stimulus	1
regulation of acute inflammatory response to antigenic stimulus	1
anterograde trans-synaptic signaling	1
behavior	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
adult behavior	1
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
positive regulation of cell adhesion	1
central nervous system neuron differentiation	1
pallium development	1
anatomical structure development	1
plasma membrane bounded cell projection organization	1
positive regulation of response to food	1
regulation of appetite	1
regulation of neurotrophin production	1
nerve growth factor production	1
myeloid leukocyte activation	1
regulation of blood pressure	1
positive regulation of amine metabolic process	1
regulation of dopamine metabolic process	1
dopamine metabolic process	1
photoperiodism	1
developmental process	1
growth	1
columnar/cuboidal epithelial cell differentiation	1
digestive tract development	1
transmembrane signaling receptor activity	1
protein binding	1
hormone activity	1
neuropeptide activity	1

Protein interactions and networks

STRING

2676 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPY	NPY1R	P25929	999
NPY	NPY2R	P49146	998
NPY	LEP	P41159	996
NPY	NPY5R	Q15761	996
NPY	GAL	P22466	983
NPY	GHRL	Q9UBU3	983
NPY	AGRP	O00253	976
NPY	VIP	P01282	973
NPY	POMC	P01189	973
NPY	CRH	P06850	946
NPY	SST	P01166	945
NPY	HCRT	O43612	928
NPY	TAC1	P20366	928
NPY	INS	P01308	918
NPY	MC4R	P32245	915

IntAct

21 interactions, top by confidence:

A	B	Type	Score
NR1H2	NPY	psi-mi:“MI:0915”(physical association)	0.560
UBQLN2	NPY	psi-mi:“MI:0915”(physical association)	0.560
NPY	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
NPY	UBQLN1	psi-mi:“MI:0915”(physical association)	0.440
NPY	UBQLN1	psi-mi:“MI:0403”(colocalization)	0.440
NPY	FAP	psi-mi:“MI:0194”(cleavage reaction)	0.440
NPY	DPP4	psi-mi:“MI:0194”(cleavage reaction)	0.440
ATP12A	NPY	psi-mi:“MI:0915”(physical association)	0.370
NR1H2	NPY	psi-mi:“MI:0915”(physical association)	0.370
NPY	BAG6	psi-mi:“MI:0915”(physical association)	0.370
NPY	EGFR	psi-mi:“MI:2364”(proximity)	0.270
NPY	PTEN	psi-mi:“MI:2364”(proximity)	0.270
NPY	PTPN11	psi-mi:“MI:2364”(proximity)	0.270
Bicdl1	NPY	psi-mi:“MI:0403”(colocalization)	0.270
NPY	Bicdl1	psi-mi:“MI:0403”(colocalization)	0.270
Rab6b	NPY	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (10): NR1H2 (Two-hybrid), UBQLN2 (Two-hybrid), NPY (Phenotypic Enhancement), NPY1R (Reconstituted Complex), NPY (Biochemical Activity), NPY (Two-hybrid), NPY (Two-hybrid), NPY (Two-hybrid), NR1H2 (Two-hybrid), UBQLN1 (Two-hybrid)

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

7 interactions.

A	Effect	B	Mechanism
NPY	up-regulates	NPY5R	binding
FOXO1	“up-regulates quantity by expression”	NPY	“transcriptional regulation”
NPY	down-regulates	“Food intake”
NPY	up-regulates	NPY4R	binding
NPY	up-regulates	NPY1R	binding
NPY	up-regulates	NPY2R	binding
LEPR	“down-regulates quantity”	NPY

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

865 predictions. Top by Δscore:

Variant	Effect	Δscore
7:24284276:G:GG	donor_gain	0.9900
7:24285306:G:A	acceptor_gain	0.9900
7:24285424:CAGAG:C	donor_loss	0.9900
7:24285425:AGAG:A	donor_loss	0.9900
7:24285426:GAG:G	donor_gain	0.9900
7:24285429:GTGG:G	donor_loss	0.9900
7:24285430:T:A	donor_loss	0.9900
7:24289637:G:T	donor_gain	0.9900
7:24284274:CC:C	donor_gain	0.9800
7:24284915:G:GT	donor_gain	0.9800
7:24285305:T:TA	acceptor_gain	0.9800
7:24285423:G:GT	donor_gain	0.9800
7:24285424:C:T	donor_gain	0.9800
7:24284271:CCACC:C	donor_gain	0.9700
7:24284274:CCG:C	donor_loss	0.9700
7:24284275:CGT:C	donor_loss	0.9700
7:24284276:G:GC	donor_loss	0.9700
7:24284277:T:G	donor_loss	0.9700
7:24284278:G:GC	donor_loss	0.9700
7:24284279:A:AC	donor_loss	0.9700
7:24284280:G:C	donor_loss	0.9700
7:24285236:TGCAG:T	acceptor_gain	0.9700
7:24285237:GCAGA:G	acceptor_gain	0.9700
7:24285239:AGATG:A	acceptor_gain	0.9700
7:24285427:AGGTG:A	donor_gain	0.9700
7:24291657:TTACA:T	acceptor_loss	0.9700
7:24291658:TACA:T	acceptor_loss	0.9700
7:24291659:ACAGG:A	acceptor_loss	0.9700
7:24291660:CA:C	acceptor_loss	0.9700
7:24291661:A:AC	acceptor_loss	0.9700

AlphaMissense

604 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:24285422:G:T	R61M	1.000
7:24285413:T:C	L58P	0.999
7:24285419:C:T	T60I	0.999
7:24285422:G:C	R61T	0.999
7:24285423:G:C	R61S	0.999
7:24285423:G:T	R61S	0.999
7:24285428:G:C	R63T	0.999
7:24289504:G:A	G65E	0.999
7:24285416:T:A	I59N	0.998
7:24285428:G:T	R63I	0.998
7:24289499:A:C	R63S	0.998
7:24289499:A:T	R63S	0.998
7:24285337:C:T	P33S	0.997
7:24285338:C:A	P33Q	0.997
7:24285395:T:C	L52P	0.997
7:24285407:T:A	I56N	0.997
7:24285407:T:G	I56S	0.997
7:24285416:T:G	I59S	0.997
7:24285421:A:G	R61G	0.997
7:24289504:G:T	G65V	0.997
7:24289508:A:C	K66N	0.997
7:24289508:A:T	K66N	0.997
7:24285383:A:G	Y48C	0.996
7:24285391:G:C	A51P	0.996
7:24285398:G:C	R53P	0.996
7:24285407:T:C	I56T	0.996
7:24285416:T:C	I59T	0.996
7:24285418:A:G	T60A	0.996
7:24289503:G:A	G65R	0.996
7:24289503:G:C	G65R	0.996

dbSNP variants (sampled 300 via entrez): RS1000220116 (7:24287641 T>C), RS1000322339 (7:24282226 T>G), RS1000676839 (7:24287967 T>C), RS1000941389 (7:24286759 A>C), RS1001279868 (7:24287946 A>T), RS1001664989 (7:24283255 G>A,C), RS1002009644 (7:24282912 G>A), RS1002057671 (7:24283927 T>C), RS1002160276 (7:24288533 T>G), RS1002609087 (7:24284089 C>A,G), RS1003069846 (7:24284261 C>A,T), RS1003119492 (7:24289680 T>C), RS1003277998 (7:24284527 T>C), RS1003283858 (7:24290898 C>T), RS1004017675 (7:24285095 G>A)

Disease associations

OMIM: gene MIM:162640 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001888_1	Periodontitis	4.000000e-07
GCST002602_2	Vitamin D levels	1.000000e-06
GCST002635_1	Aggressive periodontitis (sex interaction)	4.000000e-06
GCST007565_73	Morning person	2.000000e-18
GCST007576_362	Chronotype	2.000000e-18
GCST010988_151	Adult body size	2.000000e-08
GCST010989_116	Body size at age 10	4.000000e-15
GCST012166_6	Adiponectin levels	7.000000e-06
GCST90000047_135	Age at first sexual intercourse	3.000000e-11
GCST90011892_6	Retinitis pigmentosa	8.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0008343	sex interaction measurement
EFO:0008328	chronotype measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004502	adiponectin measurement
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Binding affinities (BindingDB)

4 measured of 4 human assays (5 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
PYY Pro34, Human	KI	0.14 nM
CAS_118997-30-1	KI	0.17 nM
CAS_59763-91-6	KI	209 nM
NSC_41735	KI	468 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
trichostatin A	increases expression, affects cotreatment	3
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	affects cotreatment, increases expression, decreases expression	2
arsenite	increases methylation	1
sodium arsenite	affects cotreatment, increases expression	1
linalool	increases expression	1
mercuric bromide	affects cotreatment, increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Limonene	decreases expression	1
Arsenic Trioxide	increases expression	1
Orlistat	increases expression	1
Adenosine Triphosphate	affects response to substance	1
Antivenins	decreases reaction, increases hydrolysis	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases expression	1
Cytarabine	decreases expression	1
Chlorpyrifos	affects expression, affects response to substance	1
Guanethidine	decreases secretion	1
Hydrocortisone	affects expression	1
Norepinephrine	affects response to substance	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	increases expression	1
Scorpion Venoms	decreases reaction, increases hydrolysis	1

Clinical trials (associated diseases)

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