CARTPT

Summary

CARTPT (CART prepropeptide, HGNC:24323) is a protein-coding gene on chromosome 5q13.2, encoding Cocaine- and amphetamine-regulated transcript protein (Q16568). Satiety factor closely associated with the actions of leptin and neuropeptide Y; this anorectic peptide inhibits both normal and starvation-induced feeding and completely blocks the feeding response induced by neuropeptide Y and regulated by leptin in the hypothalamus.

This gene encodes a preproprotein that is proteolytically processed to generate multiple biologically active peptides. These peptides play a role in appetite, energy balance, maintenance of body weight, reward and addiction, and the stress response. Expression of a similar gene transcript in rodents is upregulated following administration of cocaine and amphetamine. Mutations in this gene are associated with susceptibility to obesity in humans.

Source: NCBI Gene 9607 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited obesity (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 29 total
• Phenotypes (HPO): 6
• MANE Select transcript: NM_004291

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24323
Approved symbol	CARTPT
Name	CART prepropeptide
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Aliases	CART
Ensembl gene	ENSG00000164326
Ensembl biotype	protein_coding
OMIM	602606
Entrez	9607

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000296777, ENST00000513096

RefSeq mRNA: 1 — MANE Select: NM_004291 NM_004291

CCDS: CCDS4011

Canonical transcript exons

ENST00000296777 — 3 exons

Exon	Start	End
ENSE00001083530	71719880	71719963
ENSE00001306358	71719275	71719452
ENSE00003474230	71720508	71721045

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 97.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.7777 / max 385.9648, expressed in 147 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56878	2.7695	145
56879	0.0081	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.80	gold quality
hypothalamus	UBERON:0001898	92.80	gold quality
middle temporal gyrus	UBERON:0002771	90.98	gold quality
right frontal lobe	UBERON:0002810	90.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.82	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.58	gold quality
amygdala	UBERON:0001876	86.43	gold quality
ascending aorta	UBERON:0001496	86.33	gold quality
thoracic aorta	UBERON:0001515	86.00	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	85.85	gold quality
inferior olivary complex	UBERON:0002127	84.49	silver quality
Brodmann (1909) area 10	UBERON:0013541	83.17	gold quality
Ammon’s horn	UBERON:0001954	82.94	gold quality
frontal cortex	UBERON:0001870	82.78	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.34	gold quality
cerebral cortex	UBERON:0000956	82.28	gold quality
nucleus accumbens	UBERON:0001882	82.00	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.74	gold quality
Brodmann (1909) area 23	UBERON:0013554	81.64	gold quality
lower esophagus	UBERON:0013473	81.42	gold quality
temporal lobe	UBERON:0001871	81.39	gold quality
prefrontal cortex	UBERON:0000451	80.67	gold quality
right testis	UBERON:0004534	80.34	gold quality
neocortex	UBERON:0001950	80.18	gold quality
cortical plate	UBERON:0005343	79.60	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.43	gold quality
Brodmann (1909) area 46	UBERON:0006483	79.38	silver quality
sperm	CL:0000019	78.89	silver quality
mucosa of stomach	UBERON:0001199	78.69	gold quality
left testis	UBERON:0004533	78.43	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	10616.73
E-GEOD-137537	yes	3487.19
E-ANND-3	no	1.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, REST

miRNA regulators (miRDB)

50 targeting CARTPT, 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-3924	100.00	72.09	2394
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-1843	98.97	66.07	838

Literature-anchored findings (GeneRIF, showing 40)

• Medium-sized CART-positive neurons are common in the medial division of the shell of nucleus accumbens in monkeys. CART may be involved in neuronal and behavioural changes that underlie addiction to psychomotor stimulants and feeding. (PMID:10235641)
• The solution structure of the biologically active part of CART (residues 48-89) consists of turns and loops spanned by a compact framework composed of a few small stretches of antiparallel beta-sheet common to cystine knots. (PMID:11478874)
• genetic variants involved in weight gain, development of obesity (PMID:11791158)
• Review. The genetics of CART and its role in reward, stress, and feeding behavior are reviewed. (PMID:12147208)
• AvaII polymorphism (rs2239670) in intron 1 of the CART gene is associated with alcoholism in the Korean male population. (PMID:15234472)
• Mutating codon 34 of human proCART alters the levels of CART peptides in transfected AtT20 cells. (PMID:15326462)
• CART SNP -3608T>C may possibly contribute to the genetic risk for obesity in the Caucasian population (PMID:15823203)
• CART has a role in the control of appetite [review] (PMID:16102267)
• Cocaine- and amphetamine-regulated transcript peptides (55 to 102 & 62 to 102) are neurotransmitters with roles in a number of processes, including drug abuse by virtue of the fact that they are modulators of mesolimbic function [Review] (PMID:16146347)
• Obesity observed in humans bearing the Leu34Phe mutation could be due to a putative deficiency in hypothalamic bioactive CART. (PMID:16210370)
• analysis of CART binding sites on HepG2 cells and mouse hypothalamic dissociated cells (PMID:16309793)
• CART signaling is the main molecular pathway accounting for the decrease in bone resorption leading to high bone mass in mice and humans deficient in Mc4r (PMID:16614075)
• The anatomy of CART-containing neurons in the human infundibular nucleus raises the question as to whether this is asssociated with neuropeptide Y and agouti related protein. (PMID:17525122)
• reviews the localization of CART mRNA expression in the human brain and its possible relevance to human cocaine abuse [review] (PMID:17631364)
• This study do not support an association of the CARTPT gene with cocaine dependence. (PMID:18572320)
• Data show that CSF CART levels are significantly reduced by 30% in Dementia with Lewy bodies patients compared to controls as well as to Alzheimer’s disease patients using radioimmunoassay. (PMID:19356602)
• Our results supported the hypothesis that inherited variations of the CART gene could influence the development of obesity also in Italian children. (PMID:20151954)
• genetic variants in the CART gene may not play a major role in the vulnerability of schizophrenia subjects to concurrent alcohol use disorders and nicotine dependence. (PMID:20362026)
• No significant correlations are found between cerebrospinal fluid levels of orexin A and CART, fatigue, and hypersomnolence in multiple sclerosis patients. (PMID:21605873)
• This study demonistrated thatsex difference in CART dynamic expressions in the midbrain of drug-free depressed suicide victims. (PMID:21803054)
• CART is produced in the majority of neuroendocrine tumors, regardless of tumor origin. (PMID:21832817)
• The CART c.517A–>G polymorphism was significantly associated with obesity susceptibility. (PMID:21921635)
• It was shown that cocaine- and amphetamine-regulated transcript protein (CART) increases the transcriptional activity of estrogen receptor alpha and that CART stimulates an autocrine/paracrine loop within tumor cells to amplify the CART signal. (PMID:22139072)
• CART is an antioxidant peptide (PMID:22235287)
• The first report on the presence of CART-IR structures in the normal human pancreas. (PMID:22257587)
• Serum CART can be detected in both diabetic and non-diabetic human pregnancy and may play an important role in body mass regulation in pregnancy. (PMID:22332848)
• Family-based association study failed to observe a statistically significant association for any of the genotyped SNPs in the CARTPT gene and attention-deficit hyperactivity disorder. (PMID:22436349)
• Expression of CART in small bowel carcinoid tumors is associated with worse survival. (PMID:22553341)
• a detailed description of the CART distribution pattern within the human alimentary tract. (PMID:23034261)
• Ischemia insult triggered by oxygen-glucose deprivation (OGD) enhances NRSF mRNA levels and then NRSF antagonizes the CREB signaling on CART activation, leading to augmented cell death. (PMID:23086924)
• CART is expressed in nerve fibers and co-localizes with other neuronal factors in the circular muscle layer of human descending colon (PMID:23277430)
• CART SNPs (rs10515115, rs3763153, rs3857384, rs11575893, rs16871471) were not associated with antipsychotic-induced weight gain in schizophrenia patients. (PMID:24564533)
• Lower CART levels pose a risk for developing polycystic ovary syndrome. (PMID:24995854)
• Colocalization experiments provided evidence for the presence of cocaine- and amphetamine-regulated transcript (CART) in KP-immunoreactive (IR) and perikarya and in KP-IR and NKB-IR axon varicosities. (PMID:25084101)
• In schizophrenia patients on clozapine monotherapy, CART levels did not correlate with age, weight, BMI, abdominal, waist and hip circumferences, WHR, blood pressure, clozapine dose or treatment duration, body composition, or markers of insulin resistance (PMID:25219614)
• polymorphisms in the gene may be useful in identifying women at risk for osteoporosis. (PMID:25871004)
• In samples from patients undergoing IVF, there is a significant positive correlation between patient BMI, CART mRNA expression in granulosa cells, and CART peptide levels in follicular fluid. (PMID:26730935)
• Study conclude that CART is a regulator of glucose homeostasis and could play an important role in the pathophysiology of type 2 diabetes. Based on the ability of CART to increase insulin secretion and reduce glucagon secretion, CART-based agents could be a therapeutic modality in type 2 diabetes. (PMID:27338624)
• In vitro neurochemical studies provide new insights into the interactions among CART peptide, dopamine and cocaine in the nucleus accumbens by showing a direct inhibitory effect of CART on dopamine both in normal conditions and after cocaine induction, as well as an effect of CART on the dopamine metabolites DOPAC, HVA and DOPET. (PMID:28802898)
• Data suggest that the stress of intermittent hypoxia up-regulates expression of mRNA and protein for POMC and CART in neuronal cell lines; GATA2 and GATA3 appear to be involved in these stress mechanisms. (POMC = proopiomelanocortin; CART = cocaine- and amphetamine-regulated transcript protein; GATA2 = endothelial transcription factor GATA-2; GATA3 = T-cell-specific transcription factor GATA-3) (PMID:29275211)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cart3	ENSDARG00000035852
danio_rerio	cart2	ENSDARG00000045832
danio_rerio	cart1	ENSDARG00000070930
danio_rerio	CARTPT	ENSDARG00000104363
mus_musculus	Cartpt	ENSMUSG00000021647
rattus_norvegicus	Cartpt	ENSRNOG00000017712

Protein

Protein identifiers

Cocaine- and amphetamine-regulated transcript protein — Q16568 (reviewed: Q16568)

All UniProt accessions (1): Q16568

UniProt curated annotations — full annotation on UniProt →

Function. Satiety factor closely associated with the actions of leptin and neuropeptide Y; this anorectic peptide inhibits both normal and starvation-induced feeding and completely blocks the feeding response induced by neuropeptide Y and regulated by leptin in the hypothalamus. It promotes neuronal development and survival in vitro.

Subcellular location. Secreted.

Tissue specificity. Hypothalamus. Found in neurons of the ventrolateral part of the arcuate nucleus, in the external zone of the median eminence, and also found in terminals in the periventricular part of the paraventricular nucleus.

Induction. By leptin.

Similarity. Belongs to the CART family.

RefSeq proteins (1): NP_004282* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009106	CART	Family
IPR036722	CART_C_sf	Homologous_superfamily

Pfam: PF06373

UniProt features (16 total): sequence variant 3, strand 3, disulfide bond 3, peptide 2, modified residue 2, signal peptide 1, chain 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1HY9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16568-F1	73.81	0.23

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 (2): 41, 48

Disulfide bonds (3): 82–100, 88–108, 102–115

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 373 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CIRCADIAN_RHYTHM, MODULE_92, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_RESPONSE_TO_ETHANOL, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_COGNITION, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_RESPONSE_TO_ESTRADIOL

GO Biological Process (60): intracellular glucose homeostasis (GO:0001678), regulation of heart rate by chemical signal (GO:0003062), regulation of systemic arterial blood pressure by neurotransmitter (GO:0003070), glucose metabolic process (GO:0006006), cAMP biosynthetic process (GO:0006171), intracellular calcium ion homeostasis (GO:0006874), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), neuropeptide signaling pathway (GO:0007218), cell-cell signaling (GO:0007267), chemical synaptic transmission (GO:0007268), adult feeding behavior (GO:0008343), cellular response to starvation (GO:0009267), response to glucose (GO:0009749), regulation of circadian sleep/wake cycle, wakefulness (GO:0010840), response to food (GO:0032094), negative regulation of appetite (GO:0032099), positive regulation of epinephrine secretion (GO:0032812), response to insulin (GO:0032868), circadian regulation of gene expression (GO:0032922), operant conditioning (GO:0035106), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), negative regulation of locomotion (GO:0040013), regulation of circadian sleep/wake cycle, REM sleep (GO:0042320), drinking behavior (GO:0042756), response to morphine (GO:0043278), positive regulation of MAPK cascade (GO:0043410), response to corticotropin-releasing hormone (GO:0043435), regulation of circadian sleep/wake cycle, non-REM sleep (GO:0045188), response to ethanol (GO:0045471), negative regulation of osteoclast differentiation (GO:0045671), positive regulation of blood pressure (GO:0045777), negative regulation of bone resorption (GO:0045779), positive regulation of exocytosis (GO:0045921), negative regulation of D-glucose import across plasma membrane (GO:0046325), regulation of lipid biosynthetic process (GO:0046890), behavioral response to cocaine (GO:0048148), detection of temperature stimulus involved in sensory perception of pain (GO:0050965), detection of chemical stimulus involved in sensory perception of pain (GO:0050968), regulation of lipid catabolic process (GO:0050994)

GO Molecular Function (3): neuropeptide hormone activity (GO:0005184), molecular_function (GO:0003674), protein binding (GO:0005515)

GO Cellular Component (6): obsolete extracellular space (GO:0005615), secretory granule (GO:0030141), neuronal cell body (GO:0043025), synapse (GO:0045202), extracellular region (GO:0005576), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
signaling	2
cellular anatomical structure	2
glucose homeostasis	1
intracellular chemical homeostasis	1
regulation of heart rate	1
nervous system process involved in regulation of systemic arterial blood pressure	1
regulation of systemic arterial blood pressure mediated by a chemical signal	1
hexose metabolic process	1
purine ribonucleotide biosynthetic process	1
cyclic nucleotide biosynthetic process	1
cAMP metabolic process	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
G protein-coupled receptor signaling pathway	1
anterograde trans-synaptic signaling	1
feeding behavior	1
adult behavior	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
response to hexose	1
circadian sleep/wake cycle, wakefulness	1
regulation of circadian sleep/wake cycle	1
response to nutrient levels	1
response to chemical	1
negative regulation of response to food	1
regulation of appetite	1
regulation of epinephrine secretion	1
positive regulation of catecholamine secretion	1
epinephrine secretion	1
response to peptide hormone	1
circadian rhythm	1
regulation of gene expression	1
hormone activity	1

Protein interactions and networks

STRING

3102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CARTPT	AGRP	O00253	882
CARTPT	NPY	P01303	881
CARTPT	POMC	P01189	871
CARTPT	KISS1	Q15726	864
CARTPT	LEP	P41159	847
CARTPT	LEPR	P48357	840
CARTPT	PMCH	P20382	773
CARTPT	HCRT	O43612	772
CARTPT	TRH	P20396	755
CARTPT	GHRL	Q9UBU3	720
CARTPT	MC4R	P32245	718
CARTPT	CRH	P06850	664
CARTPT	GAL	P22466	643
CARTPT	MC3R	P41968	620
CARTPT	PYY	P10082	611

IntAct

14 interactions, top by confidence:

A	B	Type	Score
MEIS2	CARTPT	psi-mi:“MI:0915”(physical association)	0.560
CARTPT	CEACAM1	psi-mi:“MI:0915”(physical association)	0.540
CEACAM6	CARTPT	psi-mi:“MI:0915”(physical association)	0.540
CEACAM1	CARTPT	psi-mi:“MI:0407”(direct interaction)	0.540
CARTPT	CEACAM6	psi-mi:“MI:0407”(direct interaction)	0.540
CEACAM6	CARTPT	psi-mi:“MI:0407”(direct interaction)	0.540
CARTPT	FAM20C	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RHBDD1	CARTPT	psi-mi:“MI:0915”(physical association)	0.400
CARTPT	MEIS1	psi-mi:“MI:0914”(association)	0.350
CARTPT	LAMC1	psi-mi:“MI:0914”(association)	0.350
MEIS2	CARTPT	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (44): SDHB (Reconstituted Complex), CARTPT (Two-hybrid), KIF3A (Affinity Capture-MS), CDKN2C (Affinity Capture-MS), CARTPT (Affinity Capture-MS), KDM5C (Affinity Capture-MS), GSK3B (Affinity Capture-MS), PRPS2 (Affinity Capture-MS), PRPS1 (Affinity Capture-MS), PDDC1 (Affinity Capture-MS), PNPO (Affinity Capture-MS), YBEY (Affinity Capture-MS), PHKB (Affinity Capture-MS), RNF31 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS)

ESM2 similar proteins: B2RZ42, D4A6L0, E1BBQ2, J3QPP8, O02695, O62827, P01346, P01356, P06307, P06881, P09535, P12755, P12843, P15473, P16611, P17936, P20959, P22444, P22692, P24854, P47878, P49002, P49192, P49705, P53366, P55107, P55108, P56388, P80560, P97737, Q05716, Q08DX6, Q16568, Q26492, Q4RU86, Q58CS8, Q5T848, Q63475, Q68RJ9, Q6DVA0

Diamond homologs: P0DUJ6, P49192, P56388, Q16568, Q68RJ9, Q9BDP9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
REST	“down-regulates quantity by repression”	CARTPT	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	2
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

433 predictions. Top by Δscore:

Variant	Effect	Δscore
5:71719449:GCTG:G	donor_gain	0.9900
5:71719942:G:GT	donor_gain	0.9900
5:71719942:GAA:G	donor_gain	0.9900
5:71719961:ATGGT:A	donor_loss	0.9900
5:71719963:GGTA:G	donor_loss	0.9900
5:71719964:G:A	donor_loss	0.9900
5:71720507:GT:G	acceptor_gain	0.9900
5:71720507:GTGT:G	acceptor_gain	0.9900
5:71719945:G:GG	donor_gain	0.9800
5:71719964:G:GG	donor_gain	0.9800
5:71720506:A:AG	acceptor_gain	0.9800
5:71720507:G:GG	acceptor_gain	0.9800
5:71719453:G:GG	donor_gain	0.9600
5:71720506:AGTGT:A	acceptor_gain	0.9600
5:71720507:GTGTG:G	acceptor_gain	0.9600
5:71719447:G:GT	donor_gain	0.9500
5:71720506:AGT:A	acceptor_gain	0.9500
5:71720507:GTG:G	acceptor_gain	0.9500
5:71719723:C:G	donor_gain	0.9400
5:71720502:TTTCA:T	acceptor_loss	0.9400
5:71720503:TTCAG:T	acceptor_loss	0.9400
5:71720504:TCAGT:T	acceptor_loss	0.9400
5:71720505:CA:C	acceptor_loss	0.9400
5:71720506:A:G	acceptor_loss	0.9400
5:71720507:G:GT	acceptor_loss	0.9400
5:71719443:G:GT	donor_gain	0.9300
5:71719450:CTGGT:C	donor_loss	0.9300
5:71719452:GGTC:G	donor_loss	0.9300
5:71719453:GT:G	donor_loss	0.9300
5:71719454:T:G	donor_loss	0.9300

AlphaMissense

736 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:71720526:T:A	C88S	1.000
5:71720527:G:C	C88S	1.000
5:71719890:T:C	L57P	0.999
5:71720526:T:C	C88R	0.999
5:71720527:G:A	C88Y	0.999
5:71720528:T:G	C88W	0.999
5:71720548:G:C	R95T	0.999
5:71720548:G:T	R95M	0.999
5:71720549:G:C	R95S	0.999
5:71720549:G:T	R95S	0.999
5:71720554:G:A	G97E	0.999
5:71720562:T:A	C100S	0.999
5:71720563:G:A	C100Y	0.999
5:71720563:G:C	C100S	0.999
5:71720568:T:C	C102R	0.999
5:71720586:T:A	C108S	0.999
5:71720587:G:A	C108Y	0.999
5:71720587:G:C	C108S	0.999
5:71720607:T:C	C115R	0.999
5:71719902:T:C	L61S	0.998
5:71720508:T:A	C82S	0.998
5:71720508:T:C	C82R	0.998
5:71720509:G:A	C82Y	0.998
5:71720509:G:C	C82S	0.998
5:71720527:G:T	C88F	0.998
5:71720530:C:A	A89E	0.998
5:71720536:G:C	R91T	0.998
5:71720537:G:C	R91S	0.998
5:71720537:G:T	R91S	0.998
5:71720553:G:A	G97R	0.998

dbSNP variants (sampled 300 via entrez): RS1000470224 (5:71721110 G>A), RS1001563020 (5:71718826 C>A), RS1002260886 (5:71719957 C>T), RS1002735857 (5:71719126 G>A), RS1005124381 (5:71720831 A>G), RS1005916536 (5:71719051 G>A), RS1006287319 (5:71717716 G>C), RS1006772056 (5:71717324 C>T), RS1008396396 (5:71718413 A>C,G), RS1008469666 (5:71718209 G>C), RS1008729672 (5:71719672 A>C,G), RS1008801965 (5:71719527 C>A,G,T), RS1009546193 (5:71720674 C>A,T), RS1009614067 (5:71718855 G>A), RS1009968208 (5:71720060 A>C,G)

Disease associations

OMIM: gene MIM:602606 | disease phenotypes: MIM:168000

GenCC curated gene-disease

Disease	Classification	Inheritance
inherited obesity	Limited	Autosomal dominant

Mondo (3): pheochromocytoma/paraganglioma syndrome 1 (MONDO:0008192), obesity disorder (MONDO:0011122), inherited obesity (MONDO:0019182)

Orphanet (3): Hereditary pheochromocytoma-paraganglioma (Orphanet:29072), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001513	Obesity
HP:0010982	Polygenic inheritance
HP:0012340	Decreased resting energy expenditure
HP:0031819	Increased waist to hip ratio

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001971_4	Hypersomnia (HLA-DQB1*06:02 negative)	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3763153	CARTPT		0.00	0
rs3857384	CARTPT		0.00	0
rs10515115	CARTPT		0.00	0
rs11575893	CARTPT		0.00	0
rs16871471	CARTPT		0.00	0

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
methylmercuric chloride	increases expression	1
terbufos	increases methylation	1
arsenite	increases methylation	1
entinostat	decreases expression	1
Cocaine	increases expression	1
Chlorpyrifos	affects expression, affects response to substance	1
Fonofos	increases methylation	1
Malathion	increases expression	1
Nicotine	decreases expression	1
Parathion	increases methylation	1
2-Naphthylamine	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00076362	PHASE4	COMPLETED	Pediatric Hypothalamic Obesity
NCT00079547	PHASE4	COMPLETED	The Safety and Effectiveness of Low and High Carbohydrate Diets
NCT00115063	PHASE4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00134303	PHASE4	COMPLETED	Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity
NCT00143936	PHASE4	COMPLETED	The Safety and Efficacy of Low and High Carbohydrate Diets
NCT00143962	PHASE4	COMPLETED	Comparison of Two Approaches to Weight Loss Follow-Up Study
NCT00152360	PHASE4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00176306	PHASE4	COMPLETED	Levofloxacin Pharmacokinetics (PK) in the Severely Obese
NCT00203450	PHASE4	COMPLETED	Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial
NCT00205504	PHASE4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00229229	PHASE4	TERMINATED	Comparison of 4 Diets in the Management of Overweight Patients With Vascular Disease
NCT00234988	PHASE4	COMPLETED	A Phase IV, Multi-Center, Open-Label Trial of Sibutramine in Combination With a Hypocaloric Diet in Obese and Overweight Thai Subjects.
NCT00264589	PHASE4	COMPLETED	Exercise Training and Cardiovascular Function in Obesity and in Type 2 Diabetes
NCT00288873	PHASE4	COMPLETED	Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity
NCT00298857	PHASE4	TERMINATED	A Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights
NCT00315146	PHASE4	COMPLETED	Optimizing Body Composition for Function in Older Adults
NCT00319202	PHASE4	TERMINATED	Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects
NCT00327912	PHASE4	UNKNOWN	Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity
NCT00352287	PHASE4	COMPLETED	Study to Determine the Effects of Human Growth Hormone and Pioglitazone in Overweight, Prediabetic Adults
NCT00353054	PHASE4	COMPLETED	Effect of Calcium/Vitamin D Supplementation on Body Weight and Fat Loss.
NCT00390637	PHASE4	COMPLETED	Diet, Obesity and Genes (DiOGenes)
NCT00415688	PHASE4	COMPLETED	Lifestyle Modification for Obesity-Related Type 2 Diabetes
NCT00433641	PHASE4	COMPLETED	Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
NCT00440375	PHASE4	COMPLETED	Effects of Rosiglitazone on Bone in Postmenopausal Diabetic Women
NCT00453557	PHASE4	COMPLETED	Mechanism of Growth Hormone Effects on Adipose Tissue
NCT00456885	PHASE4	COMPLETED	The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
NCT00463112	PHASE4	COMPLETED	Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
NCT00512187	PHASE4	COMPLETED	Moderate Weight Loss Makes Obese Patients With Severe Chronic Plaque Psoriasis Responsive to Sub-Optimal Dose of Cyclosporine: an Investigator Blinded, Controlled, Randomized Clinical Trial
NCT00516919	PHASE4	COMPLETED	Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons
NCT00522470	PHASE4	COMPLETED	Effects of Rosiglitazone on Serum Ghrelin and Peptide YY Levels
NCT00537810	PHASE4	COMPLETED	Treatment of Binge Eating in Obese Patients in Primary Care
NCT00538486	PHASE4	COMPLETED	A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients
NCT00584389	PHASE4	TERMINATED	The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
NCT00585182	PHASE4	COMPLETED	Study to Evaluate Weight-based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT
NCT00632840	PHASE4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00636142	PHASE4	COMPLETED	Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity
NCT00675987	PHASE4	COMPLETED	A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
NCT00694811	PHASE4	COMPLETED	Effects of Re-Feeding Duration on Weight Maintenance After Weight Loss With Very-Low-Energy Diets (VLEDs)
NCT00699413	PHASE4	TERMINATED	Supplements for Controlling Resistance to Insulin
NCT00729963	PHASE4	COMPLETED	Sibutramine Versus Continuous Positive Airway Pressure (CPAP)in Obstructive Sleep Apnea (OSA) Patients