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
• GTEx eGene: eQTL in 10 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 6
• Constraint (gnomAD): pLI 0.13 (intermediate), LOEUF 0.96 (unconstrained)
• MANE Select transcript: NM_004291
• Interaction hub: 2,088 STRING partners (top 7% of genes corpus-wide)

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: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000296777

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1

ENST00000296777, ENST00000513096, ENST00001091062, ENST00001091063, ENST00001091064, ENST00001138701

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.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, hypothalamus, middle temporal gyrus, frontal lobe, Brodmann (1909) area 9.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CARTPT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	5.3e-67	-0.68	5:71719119:A:G
Testis	sqtl	7.6e-17	+0.88	5:71719119:A:G
Esophagus Muscularis	eqtl	1.9e-16	-0.28	5:71727614:T:C
Thyroid	eqtl	3.6e-12	+0.29	5:71704086:G:A
Colon Sigmoid	eqtl	2.7e-10	-0.41	5:71749415:A:T
Artery Aorta	eqtl	2.3e-07	+0.24	5:71443500:G:A
Colon Transverse	eqtl	2.9e-04	-0.17	5:71742597:T:C
Esophagus Gastroesophageal Junction	eqtl	6.8e-04	-0.19	5:71727614:T:C
Artery Tibial	eqtl	1.5e-03	+0.18	5:71627179:G:T
Pituitary	eqtl	7.0e-03	-0.27	5:71680559:G:A
Prostate	eqtl	4.1e-02	+0.28	5:71449209:C:T

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 275 tissues 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
superior frontal gyrus	UBERON:0002661	78.38	gold quality
descending thoracic aorta	UBERON:0002345	77.96	gold quality
male germ cell	CL:0000015	77.82	silver quality
forebrain	UBERON:0001890	77.54	gold quality
telencephalon	UBERON:0001893	77.45	gold quality
right adrenal gland	UBERON:0001233	77.34	gold quality
lateral nuclear group of thalamus	UBERON:0002736	76.93	gold quality
primary visual cortex	UBERON:0002436	76.90	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	76.55	gold quality
testis	UBERON:0000473	76.53	gold quality
frontal pole	UBERON:0002795	75.60	gold quality
spinal cord	UBERON:0002240	74.85	gold quality
sigmoid colon	UBERON:0001159	74.70	gold quality
entorhinal cortex	UBERON:0002728	74.51	silver quality
cingulate cortex	UBERON:0003027	73.70	gold quality
anterior cingulate cortex	UBERON:0009835	73.44	gold quality
left adrenal gland	UBERON:0001234	73.15	gold quality
left adrenal gland cortex	UBERON:0035825	73.07	gold quality
adrenal gland	UBERON:0002369	72.61	gold quality
occipital lobe	UBERON:0002021	72.53	gold quality
central nervous system	UBERON:0001017	71.96	gold quality
brain	UBERON:0000955	71.87	gold quality
superior vestibular nucleus	UBERON:0007227	71.33	gold quality
adrenal cortex	UBERON:0001235	70.77	gold quality
vermiform appendix	UBERON:0001154	70.24	gold quality
CA1 field of hippocampus	UBERON:0003881	69.54	silver quality
orbitofrontal cortex	UBERON:0004167	69.02	silver quality
islet of Langerhans	UBERON:0000006	68.77	gold quality
aorta	UBERON:0000947	68.49	gold quality
pituitary gland	UBERON:0000007	68.10	gold quality
adenohypophysis	UBERON:0002196	68.09	gold quality
medulla oblongata	UBERON:0001896	68.07	silver quality
adult organism	UBERON:0007023	67.76	silver quality
caecum	UBERON:0001153	67.25	gold quality
prostate gland	UBERON:0002367	66.66	gold quality
right adrenal gland cortex	UBERON:0035827	66.26	gold quality
dorsal plus ventral thalamus	UBERON:0001897	65.50	gold quality
left lobe of thyroid gland	UBERON:0001120	65.13	gold quality
right lobe of thyroid gland	UBERON:0001119	64.98	gold quality
fundus of stomach	UBERON:0001160	64.17	gold quality
colon	UBERON:0001155	64.16	gold quality
large intestine	UBERON:0000059	63.68	gold quality
thyroid gland	UBERON:0002046	63.66	gold quality
substantia nigra	UBERON:0002038	63.55	gold quality
midbrain	UBERON:0001891	62.56	gold quality
triceps brachii	UBERON:0001509	62.27	gold quality
stomach	UBERON:0000945	62.16	gold quality
hair follicle	UBERON:0002073	62.12	gold quality
olfactory bulb	UBERON:0002264	61.86	gold quality
oocyte	CL:0000023	61.77	gold quality
endothelial cell	CL:0000115	61.68	gold quality
type B pancreatic cell	CL:0000169	61.67	gold quality
body of stomach	UBERON:0001161	61.14	gold quality
gluteal muscle	UBERON:0002000	61.07	gold quality
smooth muscle tissue	UBERON:0001135	60.99	gold quality
cerebellar vermis	UBERON:0004720	60.60	gold quality
intestine	UBERON:0000160	60.56	gold quality
tibialis anterior	UBERON:0001385	60.31	silver quality
deltoid	UBERON:0001476	60.11	silver quality
biceps brachii	UBERON:0001507	60.01	gold quality
putamen	UBERON:0001874	59.94	gold quality
pancreatic ductal cell	CL:0002079	59.26	silver quality
thymus	UBERON:0002370	58.30	gold quality
caudate nucleus	UBERON:0001873	57.75	gold quality
transverse colon	UBERON:0001157	57.49	gold quality
diaphragm	UBERON:0001103	57.12	gold quality
esophagus	UBERON:0001043	56.82	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	56.66	gold quality
decidua	UBERON:0002450	56.55	gold quality
superficial temporal artery	UBERON:0001614	56.08	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

HPA expression

RNA tissue specificity: Tissue enriched

57 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Locus coeruleus	tissue	389.9
Hippocampal formation	tissue	307.9
Adrenal gland	tissue	111.9	high
Amygdala	tissue	89.4
Cerebral cortex	tissue	74.8	medium
Temporal cortex	tissue	74.8
Hypothalamus	tissue	63.9	high
Septum	tissue	62.5
Midbrain	tissue	42.0
Periaqueductal gray	tissue	38.6
Somatosensory cortex	tissue	38.0
Motor cortex	tissue	30.9
Hippocampus	tissue	29.7	not detected
Entorhinal cortex	tissue	28.7
Prefrontal cortex	tissue	27.1
Olfactory bulb	tissue	25.9
Postcentral gyrus	tissue	25.2
Retrosplenial and cingulate cortex	tissue	23.5
Ventral forebrain	tissue	23.1
Occipital cortex	tissue	23.1
Retina	tissue	19.8
Insular cortex	tissue	19.3
Nucleus accumbens	tissue	15.5
Retrosplenial cortex	tissue	15.5
Pons	tissue	14.4
Medulla oblongata	tissue	14.4
Smooth muscle	tissue	14.1	not detected
Frontal cortex	tissue	13.5
Breast	tissue	8.8	not detected
Putamen	tissue	8.5
Caudate putamen	tissue	7.9
Spinal cord	tissue	7.1
Basal ganglia	tissue	6.7	not detected
Substantia nigra	tissue	6.6
Superior colliculi	tissue	5.9
Pituitary gland	tissue	5.2
Thalamus	tissue	5.1
Thyroid gland	tissue	5.1	not detected
Duodenum	tissue	5.1	not detected
Prostate	tissue	4.7	not detected
Rectum	tissue	4.3	not detected
Appendix	tissue	4.1	not detected
Testis	tissue	2.9	not detected
Choroid plexus	tissue	2.9
Adipose tissue	tissue	2.3	not detected
Corpus callosum	tissue	2.3
Stomach 1	tissue	2.0	not detected
Colon	tissue	2.0	not detected
Small intestine	tissue	1.4	not detected
Epididymis	tissue	0.7	not detected
Pancreas	tissue	0.5	not detected
Vagina	tissue	0.4	not detected
Fallopian tube	tissue	0.4	not detected
Esophagus	tissue	0.3	not detected
Gallbladder	tissue	0.2	not detected
Thymus	tissue	0.2
Cerebellum	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Ventral hippocampus (307.9), Paraventricular nucleus (265.3), Lateral hypothalamic area (239.5), Dorsal raphe nucleus (219.7), Ventral posteromedial thalamic nucleus (204.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, REST

miRNA regulators (miRDB)

Targeting CARTPT by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 50 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.127, LOEUF 0.956, missense Z 0.44 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000296777 — one region, missense o/e 0.95.

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

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cart1	ENSDARG00000070930
danio_rerio		ENSDARG00000104363
mus_musculus	Cartpt	ENSMUSG00000021647
rattus_norvegicus	Cartpt	ENSRNOG00000017712

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1351330) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 16 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal cecum morphology	1
increased body weight	1
cataract	1
increased circulating insulin level	1
abnormal kidney morphology	1
abnormal vitreous body morphology	1
small kidney	1
decreased insulin secretion	1
decreased bone mass	1
abnormal osteoclast morphology	1
increased osteoclast cell number	1
impaired glucose tolerance	1
abnormal food intake	1
increased susceptibility to diet-induced obesity	1
enhanced contextual conditioning behavior	1
increased total body fat amount	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q68RJ9	100.0%	Diamond
Sus scrofa	Q9BDP9	100.0%	Diamond
Thalassophryne nattereri	P0DUJ6	54.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MCCC2	protein-coding	64087
BDP1	protein-coding	55814

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 by resolution:

PDB	Title	Method	Resolution (Å)
1HY9	COCAINE AND AMPHETAMINE REGULATED TRANSCRIPT	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted secreted proteins, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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)

Type	Positions
Phosphotyrosine	41
Phosphoserine	48

Disulfide bonds (3)

Type	Positions
Disulfide bond	82–100, 88–108, 102–115

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 (58): 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), response to corticosterone (GO:0051412), negative regulation of cytosolic calcium ion concentration (GO:0051481), positive regulation of transmission of nerve impulse (GO:0051971), negative regulation of glucagon secretion (GO:0070093), somatostatin secretion (GO:0070253), cellular response to estradiol stimulus (GO:0071392), regulation of locomotion involved in locomotory behavior (GO:0090325), negative regulation of relaxation of smooth muscle (GO:1901081), negative regulation of eating behavior (GO:1903999), positive regulation of type B pancreatic cell proliferation (GO:1904692), conditioned place preference (GO:1990708), negative regulation of type B pancreatic cell apoptotic process (GO:2000675), circadian rhythm (GO:0007623), positive regulation of cell communication (GO:0010647), regulation of exocytosis (GO:0017157), response to starvation (GO:0042594), regulation of insulin secretion (GO:0050796), response to glucocorticoid (GO:0051384)

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

GO Cellular Component (5): secretory granule (GO:0030141), neuronal cell body (GO:0043025), synapse (GO:0045202), extracellular region (GO:0005576), cytoplasm (GO:0005737)

GO top-level categories

48 GO namespaces:

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
neuropeptide activity	1
binding	1
endomembrane system	1
secretory vesicle	1
somatodendritic compartment	1
cell body	1
cell junction	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 67 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
intracellular glucose homeostasis	BP	direct assay
negative regulation of bone resorption	BP	mutant phenotype
positive regulation of blood pressure	BP	direct assay
positive regulation of epinephrine secretion	BP	direct assay
positive regulation of transmission of nerve impulse	BP	direct assay
secretory granule	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 2,088 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CARTPT	AGRP	O00253	881
CARTPT	NPY	P01303	881
CARTPT	KISS1	Q15726	866
CARTPT	POMC	P01189	858
CARTPT	LEP	P41159	809
CARTPT	LEPR	P48357	789
CARTPT	HCRT	O43612	754
CARTPT	PMCH	P20382	752
CARTPT	GHRL	Q9UBU3	717
CARTPT	MC4R	P32245	716
CARTPT	CRH	P06850	655
CARTPT	GAL	P22466	652
CARTPT	PYY	P10082	606
CARTPT	TRH	P20396	606
CARTPT	CRTC1	Q6UUV9	588

IntAct

Human interaction partners of CARTPT in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
MEIS2	physical association	0.560	3
CEACAM1	physical association	0.540	3
CEACAM6	physical association	0.540	3
FAM20C	phosphorylation reaction	0.440	1
RHBDD1	physical association	0.400	1
LAMC1	association	0.350	1
MEIS1	association	0.350	1

BioGRID (44 interactions; top human partners by supporting records): CDK5RAP3 (Affinity Capture-MS), CDKN2C (Affinity Capture-MS), CEACAM1 (Reconstituted Complex), CEACAM6 (Reconstituted Complex), COL6A1 (Affinity Capture-MS), DUSP3 (Affinity Capture-MS), ECI2 (Affinity Capture-MS), FTO (Affinity Capture-MS), GSK3B (Affinity Capture-MS), IBA57 (Affinity Capture-MS), IDH3B (Affinity Capture-MS), KDM5C (Affinity Capture-MS), KIF3A (Affinity Capture-MS), LAMC1 (Affinity Capture-MS), LETM1 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

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

Disease & clinical

Genetic variants

Variant evidence for CARTPT: 29 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 262):

Position(s)	Effect	Δscore	Sites
5:71719964–71719965	donor_loss	0.9900	6
5:71719453–71719454	donor_loss	0.9500	5
5:71719454	donor_loss	0.9400
5:71719723	donor_gain	0.9400
5:71720506–71720507	acceptor_loss	0.9400	6
5:71719944	donor_gain	0.9300
5:71719457	donor_loss	0.9100
5:71719452	donor_loss	0.8900
5:71719457–71719458	donor_loss	0.8900	3
5:71719966	donor_loss	0.8800

AlphaMissense

296 missense substitutions predicted likely pathogenic (of 736 scored), across 67 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
C88	7	0.998	1.000
C108	7	0.998	0.999
C102	7	0.997	0.999
C100	7	0.996	0.999
C115	7	0.995	0.999
C82	7	0.994	0.998
R95	7	0.992	0.999
F111	7	0.959	0.994
R91	7	0.938	0.998
N109	7	0.930	0.998
D101	7	0.879	0.949
G97	6	0.996	0.999
L61	6	0.968	0.998
G85	6	0.960	0.996
K114	6	0.960	0.994
K92	6	0.950	0.994
G93	6	0.946	0.996
K75	6	0.940	0.982
A89	6	0.939	0.998
L64	6	0.931	0.995

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Breast Invasive Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Stomach Adenocarcinoma (TCGA)	unfavorable	0.000321

Disease associations

OMIM: gene MIM:602606 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
inherited obesity	Limited	Autosomal dominant	2

Mondo (1): inherited obesity (MONDO:0019182)

HPO phenotypes

6 phenotypes (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:

Study	Trait	p-value
GCST001971_4	Hypersomnia (HLA-DQB1*06:02 negative)	3e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 310 trials:

NCT	Phase	Status	Title
NCT00076362	Phase 4	COMPLETED	Pediatric Hypothalamic Obesity
NCT00079547	Phase 4	COMPLETED	The Safety and Effectiveness of Low and High Carbohydrate Diets
NCT00115063	Phase 4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00134303	Phase 4	COMPLETED	Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity
NCT00143936	Phase 4	COMPLETED	The Safety and Efficacy of Low and High Carbohydrate Diets
NCT00143962	Phase 4	COMPLETED	Comparison of Two Approaches to Weight Loss Follow-Up Study
NCT00152360	Phase 4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00176306	Phase 4	COMPLETED	Levofloxacin Pharmacokinetics (PK) in the Severely Obese
NCT00203450	Phase 4	COMPLETED	Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial
NCT00205504	Phase 4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00229229	Phase 4	TERMINATED	Comparison of 4 Diets in the Management of Overweight Patients With Vascular Disease
NCT00234988	Phase 4	COMPLETED	A Phase IV, Multi-Center, Open-Label Trial of Sibutramine in Combination With a Hypocaloric Diet in Obese and Overweight Thai Subjects.
NCT00264589	Phase 4	COMPLETED	Exercise Training and Cardiovascular Function in Obesity and in Type 2 Diabetes
NCT00288873	Phase 4	COMPLETED	Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity
NCT00298857	Phase 4	TERMINATED	A Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights
NCT00315146	Phase 4	COMPLETED	Optimizing Body Composition for Function in Older Adults
NCT00319202	Phase 4	TERMINATED	Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects
NCT00327912	Phase 4	UNKNOWN	Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity
NCT00352287	Phase 4	COMPLETED	Study to Determine the Effects of Human Growth Hormone and Pioglitazone in Overweight, Prediabetic Adults
NCT00353054	Phase 4	COMPLETED	Effect of Calcium/Vitamin D Supplementation on Body Weight and Fat Loss.
NCT00390637	Phase 4	COMPLETED	Diet, Obesity and Genes (DiOGenes)
NCT00415688	Phase 4	COMPLETED	Lifestyle Modification for Obesity-Related Type 2 Diabetes
NCT00433641	Phase 4	COMPLETED	Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
NCT00440375	Phase 4	COMPLETED	Effects of Rosiglitazone on Bone in Postmenopausal Diabetic Women
NCT00453557	Phase 4	COMPLETED	Mechanism of Growth Hormone Effects on Adipose Tissue
NCT00456885	Phase 4	COMPLETED	The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
NCT00463112	Phase 4	COMPLETED	Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
NCT00512187	Phase 4	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	Phase 4	COMPLETED	Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons
NCT00522470	Phase 4	COMPLETED	Effects of Rosiglitazone on Serum Ghrelin and Peptide YY Levels
NCT00537810	Phase 4	COMPLETED	Treatment of Binge Eating in Obese Patients in Primary Care
NCT00538486	Phase 4	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	Phase 4	TERMINATED	The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
NCT00585182	Phase 4	COMPLETED	Study to Evaluate Weight-based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT
NCT00632840	Phase 4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00636142	Phase 4	COMPLETED	Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity
NCT00675987	Phase 4	COMPLETED	A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
NCT00694811	Phase 4	COMPLETED	Effects of Re-Feeding Duration on Weight Maintenance After Weight Loss With Very-Low-Energy Diets (VLEDs)
NCT00699413	Phase 4	TERMINATED	Supplements for Controlling Resistance to Insulin
NCT00729963	Phase 4	COMPLETED	Sibutramine Versus Continuous Positive Airway Pressure (CPAP)in Obstructive Sleep Apnea (OSA) Patients
NCT00752726	Phase 4	COMPLETED	Effect of Orlistat in Body Composition
NCT00770328	Phase 4	COMPLETED	The Effects of Pentoxifylline on PAI-1 in an Obese Population
NCT00775164	Phase 4	WITHDRAWN	Pioglitazone Therapy in Obese Children With Insulin Resistance: A Randomized, Controlled Pilot Study
NCT00775814	Phase 4	COMPLETED	Efficacy of Candesartan on Reducing Blood Pressure in Insulin-Resistant, Obese Patients With Hypertension.
NCT00779844	Phase 4	TERMINATED	Anesthesic Propofol and Remifentanil Requirements in Obese Patients
NCT00788840	Phase 4	COMPLETED	Detemir Energy Expenditure Study
NCT00790946	Phase 4	UNKNOWN	Kagoshima Collaborate Trial in Metabolic Syndrome (KACT Study)
NCT00841217	Phase 4	COMPLETED	Regulation of Lipoprotein Transport in Metabolic Syndrome
NCT00845559	Phase 4	WITHDRAWN	The Effects of Exenatide on Post-Meal Sugar Peaks and Vascular Health in Obese/Pre-Diabetic Young Adults
NCT00847262	Phase 4	COMPLETED	Trial Comparing Metabolic Effects of Telmisartan and Amlodipine on Hypertensive Patients With Obesity and Diabetes
NCT00852384	Phase 4	COMPLETED	Non Invasive Pressure Support Ventilation (NIPPV) Versus Recruitment Maneuver (RM) and Preoxygenation
NCT00877123	Phase 4	COMPLETED	Effect of Vitamin D Supplementation on Fasting Glucose and Interleukin-10 (IL-10) in Arab Women With Impaired Fasting Glucose
NCT00883259	Phase 4	UNKNOWN	Metformin and Gestational Diabetes in High-risk Patients: a RCTs
NCT00917033	Phase 4	COMPLETED	Tracheal Intubation of Morbidly Obese Patients. GlideScope Versus Direct Laryngoscopy
NCT00928005	Phase 4	COMPLETED	Evaluating the Effects of a Diet and Exercise Program in People With Type 2 Diabetes or Prediabetes: (The SHAPE3 Study)
NCT00932022	Phase 4	COMPLETED	Trospium Chloride XR in Obese Female Patients With Overactive Bladder
NCT00934570	Phase 4	COMPLETED	Activity and Metformin Intervention in Obese Adolescents
NCT00943969	Phase 4	COMPLETED	Determinants of Oral Morphine Answer Among Obese Patients Before and After Gastric Bypass
NCT00959309	Phase 4	COMPLETED	Media Use in Preschooler Study (MUPS)
NCT00983970	Phase 4	COMPLETED	Effects of Interactive Video Game Cycling on Obese Adolescent Health