MC2R

Summary

MC2R (melanocortin 2 receptor, HGNC:6930) is a protein-coding gene on chromosome 18p11.21, encoding Adrenocorticotropic hormone receptor (Q01718). G protein-coupled receptor for corticotropin/ACTH, primarily expressed in adrenal cortex where it plays a key role in the regulation of adrenocortical function.

MC2R encodes one member of the five-member G-protein associated melanocortin receptor family. Melanocortins (melanocyte-stimulating hormones and adrenocorticotropic hormone) are peptides derived from pro-opiomelanocortin (POMC). MC2R is selectively activated by adrenocorticotropic hormone, whereas the other four melanocortin receptors recognize a variety of melanocortin ligands. Mutations in MC2R can result in familial glucocorticoid deficiency. Alternate transcript variants have been found for this gene.

Source: NCBI Gene 4158 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glucocorticoid deficiency 1 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 191 total — 17 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000529

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6930
Approved symbol	MC2R
Name	melanocortin 2 receptor
Location	18p11.21
Locus type	gene with protein product
Status	Approved
Aliases	ACTHR
Ensembl gene	ENSG00000185231
Ensembl biotype	protein_coding
OMIM	607397
Entrez	4158

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000327606, ENST00000399821, ENST00000946323, ENST00000946324, ENST00000946325

RefSeq mRNA: 2 — MANE Select: NM_000529 NM_000529, NM_001291911

CCDS: CCDS11869

Canonical transcript exons

ENST00000327606 — 2 exons

Exon	Start	End
ENSE00001297447	13882044	13885646
ENSE00001496022	13915488	13915536

Expression profiles

Bgee: expression breadth broad, 38 present calls, max score 98.93.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0479 / max 47.2897, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171291	0.0479	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	98.93	gold quality
right adrenal gland	UBERON:0001233	90.82	gold quality
left adrenal gland	UBERON:0001234	90.28	gold quality
right adrenal gland cortex	UBERON:0035827	90.11	gold quality
left adrenal gland cortex	UBERON:0035825	88.83	gold quality
adrenal gland	UBERON:0002369	88.60	gold quality
adrenal cortex	UBERON:0001235	86.97	gold quality
diaphragm	UBERON:0001103	78.54	gold quality
hair follicle	UBERON:0002073	76.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	71.64	gold quality
olfactory bulb	UBERON:0002264	70.72	gold quality
type B pancreatic cell	CL:0000169	70.60	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	68.84	gold quality
superficial temporal artery	UBERON:0001614	68.83	gold quality
epithelial cell of pancreas	CL:0000083	68.76	gold quality
triceps brachii	UBERON:0001509	67.90	gold quality
gluteal muscle	UBERON:0002000	67.79	gold quality
vastus lateralis	UBERON:0001379	66.77	gold quality
quadriceps femoris	UBERON:0001377	66.60	gold quality
biceps brachii	UBERON:0001507	65.05	gold quality
kidney epithelium	UBERON:0004819	62.94	gold quality
tibialis anterior	UBERON:0001385	62.84	silver quality
mucosa of paranasal sinus	UBERON:0005030	62.44	gold quality
myocardium	UBERON:0002349	61.55	gold quality
tongue squamous epithelium	UBERON:0006919	61.54	gold quality
cardiac muscle of right atrium	UBERON:0003379	61.53	gold quality
deltoid	UBERON:0001476	61.26	gold quality
left ventricle myocardium	UBERON:0006566	60.97	gold quality
nephron tubule	UBERON:0001231	60.50	gold quality
cervix squamous epithelium	UBERON:0006922	60.35	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CREB1, CREM, DNMT1, FOXL2, NR0B1, NR1I2, NR5A1, PBX1, PPARG, SF1, TCF3

miRNA regulators (miRDB)

128 targeting MC2R, 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-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• findings suggest a novel mechanism is involved in the constitutive activation of the melanocortin 2 receptor in which failure of desensitization appears to be associated with enhanced basal receptor activity (PMID:12456795)
• Cyclic AMP-induced regulation of transcriptional activity of gene achieved through two SF1 binding elements in proximal promoter. Regulation by angiotensin II by two AP1 binding sites. Region in promoter responsible for tissue-specific gene expression. (PMID:12530626)
• ACTH feedback loop in pituitary. Loss of expression of ACTH-R in corticotroph adenomas in Cushing’s disease may play role in resistance to feedback of pituitary-adrenal axis. (PMID:14671214)
• Study of two mutations in the same allele of MC2R associated with clinical hypersensitivity to ACTH shows that each alone produces an inactive receptor, but together lead to a receptor with a highly significant elevation in constitutive activity (PMID:15062562)
• Data show that an E-box is involved in the repression of melanocortin 2 receptor gene expression in granulosa cells through interactions with several factors. (PMID:15171714)
• We describe an ACTH receptor promoter polymorphism that results in lower promoter activity in vitro and is associated with lower cortisol secretion to prolonged ACTH stimulation in vivo. Might influence cortisol homeostasis under stress conditions. (PMID:15240582)
• DAX-1 is a major repressor of ACTH-R gene expression in vitro and in vivo. (PMID:15879363)
• Specific factors, missing in cells which do not express any melanocortin receptor, are involved in the correct addressing of human MC2R to the cell membrane. (PMID:15982783)
• Genetic variations within ACTH receptor promoter result in decreased DHEA secretion. We might have identified one of the genetic factors responsible for variation in ACTH-dependent DHEA secretion. (PMID:16260430)
• PKA and protein kinase C act synergistically to induce hMC2R desensitization, but only PKA is essential for receptor internalization (PMID:16497811)
• MC2R mutations were found in patients diagnosed with salt-losing forms of adrenal hypoplasia; these changes represent severely disruptive loss-of-function mutations including the first reported homozygous frameshift mutation (PMID:17223989)
• MC2R-green fluorescent protein fusion transfected with either MRAPalpha or MRAPbeta was impaired both in cell membrane localization and signaling. (PMID:17456795)
• Testicular adrenal rest tumors produce adrenal-specific steroids and express adrenal-specific enzymes and ACTH and AII receptors, confirming the strong resemblance with adrenal tissue. (PMID:17595257)
• Transcription factors of the CREB/CREM/ATF family have a moderate effect on human MC2-R promoter activity, but seem to play a minor role in transmitting stimulation of the cAMP pathway to increased MC2-R expression. (PMID:17712720)
• Results indicate that ACTH1-16 is the minimal peptide required for hMC2R binding and signaling. (PMID:17877367)
• Corticotrophin-releasing hormone induces ACTHR receptor as potently as ACTH during late gestation. (PMID:17959886)
• results do not support an involvement of the -2 CTC to CCC ACTH receptor promoter polymorphism in somatoform disorders (PMID:18197087)
• The MC2R promoter polymorphism modulates the hypothalamo-pituitary-adrenal axis in children and may play a role in altered regulation of adrenarche. (PMID:18356748)
• Significant differences in genotype frequency among ethnic groups studied were found for each of the six variants analyzed. the allele -184A with a protective effect from heroin addiction in Hispanics. (PMID:18359160)
• two mutations of the ACTH receptor (MC2R) gene are reported in this familial glucocorticoid deficiency clinical case. (PMID:18492762)
• In cortices attached to adrenocortical adenomas, MC2R mRNA was expressed faintly in zona fasciculata and zona reticularis. (PMID:18505908)
• The transmembrane domain of MRAP is the MC2R interaction domain and a conserved N-terminal tyrosine-rich domain of MRAP is required for trafficking MC2R to the cell surface. (PMID:18818285)
• The majority of MC2R mutations found in familial glucocorticoid deficiency type 1 fail to function because they fail to traffic to the cell surface (PMID:18840636)
• MRAP not only facilitates MC2 receptor trafficking but also allows properly localized receptor to bind ACTH and consequently signal. (PMID:18981183)
• The polymorphisms of the MC2R promoter might be one important factor that influences the efficacy of ACTH therapy on infantile spasms. (PMID:19024088)
• Includes the study of a polymorphic upstream ORF in this gene, and shows that it functions to reduce protein levels by ~37%. (PMID:19372376)
• Data show that tall stature is associated with mutations in MC2R but not in MRAP. (PMID:19558534)
• No mutations in MC2R, MRAP or STAR were identified in any patient with Addison’s disease (PMID:19903795)
• Absence of MC2R N-glycosylation abrogates to a large extent MC2R cell surface expression in the absence of accessory proteins, whereas when MC2R is N-glycosylated, it can be expressed at the plasma membrane without assistance. (PMID:20022931)
• The results showed that the haplotype TCCT in MC2R promoter significantly led to increased MC2R expression and strong responses to adrenocorticotropin hormone. (PMID:20042918)
• MC2R expression is aberrant in alopecia areata (AA). A deficit in ACTH/MC2R activity may play an important role in the pathophysiology of AA. (PMID:20590821)
• Loss of the C terminus of MC2R impairs cell surface expression and ACTH sensitivity but does not disrupt interaction of MC2R with melanocortin receptor accessory protein. (PMID:20962024)
• ACTH binding to MC2R stimulates PKA-dependent p44/p42(mapk) phosphorylation. (PMID:21195128)
• C-terminal tail of the MC(4) receptor with the corresponding regions from the MC(2) receptor resulted in MRAP-dependent signaling (PMID:21211532)
• The MC2R/MRAP2 complex requires much higher concentrations of ACTH to activate compared with the MC2R/MRAP complex. (PMID:21367968)
• Familial glucocorticoid deficiency in five Arab kindreds with homozygous point mutations of the ACTH receptor (MC2R). (PMID:21778684)
• Intracellular Ser and Thr (S/T) residues of MC2R were found to play important roles not only in plasma membrane targeting and function but also in promoting receptor internalization. (PMID:21920850)
• GRA5556G, GRA5556G, GAGG4534/4536AAAG polymorphisms and ACTHR promoter T-2C variants might be associated with quantitative trait of stress. (PMID:22357529)
• No significant difference was found between plasma lipid and glucose levels and various GR and ACTHR genotypes. (PMID:22487832)
• Our observations suggest that MC2R is involved in prostate carcinogenesis and that targeting MC2R signaling may provide a novel avenue in prostate carcinoma treatment. (PMID:22842514)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mc2r	ENSDARG00000054949
mus_musculus	Mc2r	ENSMUSG00000045569
rattus_norvegicus	Mc2r	ENSRNOG00000072071

Paralogs (18): LPAR2 (ENSG00000064547), CNR1 (ENSG00000118432), MC3R (ENSG00000124089), S1PR4 (ENSG00000125910), GPR12 (ENSG00000132975), GPR6 (ENSG00000146360), GPR119 (ENSG00000147262), MC4R (ENSG00000166603), S1PR1 (ENSG00000170989), LPAR3 (ENSG00000171517), MC5R (ENSG00000176136), S1PR5 (ENSG00000180739), GPR3 (ENSG00000181773), CNR2 (ENSG00000188822), LPAR1 (ENSG00000198121), S1PR3 (ENSG00000213694), MC1R (ENSG00000258839), S1PR2 (ENSG00000267534)

Protein

Protein identifiers

Adrenocorticotropic hormone receptor — Q01718 (reviewed: Q01718)

Alternative names: Adrenocorticotropin receptor, Melanocortin receptor 2

All UniProt accessions (2): Q01718, R4GMM0

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor for corticotropin/ACTH, primarily expressed in adrenal cortex where it plays a key role in the regulation of adrenocortical function. Upon activation, couples to G(s) protein, stimulating adenylate cyclase and activating the cAMP-dependent signaling pathway, the MAPK cascade as well as the PKA pathway, leading to steroidogenic factor 1/NR5A1-mediated transcriptional activation. Activation by ACTH facilitates the release of adrenal glucocorticoids, including cortisol and corticosterone. In addition, MC2R is required for fetal and neonatal adrenal gland development.

Subunit / interactions. Homodimer. Interacts with corticotropin/ACTH. Interacts with MRAP; this interaction targets MC2R to the plasma membrane. Interacts with MRAP2; competing with MRAP for binding to MC2R and impairing the binding of ACTH.

Subcellular location. Cell membrane.

Tissue specificity. Melanocytes and corticoadrenal tissue.

Post-translational modifications. Ubiquitinated by MGRN1 that may be involved in post-endocytic trafficking and/or degradation of internalized receptor.

Disease relevance. Glucocorticoid deficiency 1 (GCCD1) [MIM:202200] A form of glucocorticoid deficiency, a rare autosomal recessive disorder characterized by resistance to ACTH action on the adrenal cortex, adrenal insufficiency and an inability of the adrenal cortex to produce cortisol. It usually presents in the neonatal period or in early childhood with episodes of hypoglycemia and other symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, convulsions, and shock. In a small number of patients hypoglycemia can be sufficiently severe and persistent that it leads to serious long-term neurological damage or death. The diagnosis is readily confirmed with a low plasma cortisol measurement in the presence of an elevated ACTH level, and normal aldosterone and plasma renin measurements. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (2): NP_000520, NP_001278840 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001168	ACTH_rcpt	Family
IPR001671	Melcrt_ACTH_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (55 total): helix 13, sequence variant 12, topological domain 7, transmembrane region 7, mutagenesis site 4, binding site 2, glycosylation site 2, disulfide bond 2, turn 2, strand 2, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9K3L	ELECTRON MICROSCOPY	3.01
8GY7	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01718-F1	85.11	0.46

Antibody-complex structures (SAbDab): 1 — 9K3L

Functional residue map

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

Ligand- & substrate-binding residues (2): 103; 107

Post-translational modifications (1): 293

Disulfide bonds (2): 21–253, 245–251

Glycosylation sites (2): 12, 17

Mutagenesis-validated functional residues (4):

Position	Phenotype
21	significantly reduced acth binding.
245	significantly reduced acth binding.
251	significantly reduced acth binding.
253	significantly reduced acth binding.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418555	G alpha (s) signalling events
R-HSA-5579031	Defective ACTH causes obesity and POMCD
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding
R-HSA-5668914	Diseases of metabolism

MSigDB gene sets: 236 (showing top): MORF_RAGE, MORF_FLT1, CAR_TNFRSF25, GOBP_GLUCOCORTICOID_METABOLIC_PROCESS, MORF_ATRX, GOBP_REGULATION_OF_HORMONE_LEVELS, MORF_ESR1, GOBP_POSITIVE_REGULATION_OF_HORMONE_METABOLIC_PROCESS, GOBP_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, MORF_PPP5C, MORF_FANCG, GOBP_HORMONE_BIOSYNTHETIC_PROCESS

GO Biological Process (5): G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), signal transduction (GO:0007165), neuropeptide signaling pathway (GO:0007218)

GO Molecular Function (4): G protein-coupled receptor activity (GO:0004930), melanocortin receptor activity (GO:0004977), corticotropin receptor activity (GO:0004978), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Diseases of metabolism	1
Signal Transduction	1
GPCR ligand binding	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
cellular anatomical structure	2
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled peptide receptor activity	1
melanocortin receptor activity	1
neuropeptide receptor activity	1
hormone binding	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

950 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MC2R	POMC	P01189	999
MC2R	MRAP	Q8TCY5	985
MC2R	MRAP2	Q96G30	899
MC2R	CYP11B1	P15538	894
MC2R	CYP11A1	P05108	893
MC2R	CYP21A2	P04033	889
MC2R	CYP17A1	P05093	857
MC2R	CRH	P06850	842
MC2R	CYP11B2	P19099	842
MC2R	STAR	P49675	832
MC2R	HSD11B2	P80365	770
MC2R	NR0B1	P51843	751
MC2R	CRHR2	Q13324	688
MC2R	AGRP	O00253	687
MC2R	FGD3	Q5JSP0	678

IntAct

15 interactions, top by confidence:

A	B	Type	Score
MC2R	MRAP	psi-mi:“MI:0403”(colocalization)	0.620
MC2R	MRAP	psi-mi:“MI:0915”(physical association)	0.620
MRAP	MC2R	psi-mi:“MI:0915”(physical association)	0.570
MC2R	MRAP2	psi-mi:“MI:0915”(physical association)	0.570
MRAP2	MC2R	psi-mi:“MI:0915”(physical association)	0.570
MC2R	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	MC2R	psi-mi:“MI:0915”(physical association)	0.400
MC2R	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	MC2R	psi-mi:“MI:0915”(physical association)	0.400
MC2R	RAMP3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (7): MRAP (Two-hybrid), MRAP2 (Two-hybrid), MC2R (PCA), MC2R (PCA), PRPF6 (Cross-Linking-MS (XL-MS)), MGRN1 (Affinity Capture-Western), MRAP (Affinity Capture-Western)

ESM2 similar proteins: B0V1P1, O19037, O77616, O97504, P32244, P32245, P33032, P33033, P34974, P35345, P41149, P41968, P41983, P55167, P56442, P56450, P56451, P70115, P70596, P79166, Q01718, Q01727, Q0Z8I9, Q29154, Q64326, Q6A155, Q80SS9, Q80SZ5, Q864F7, Q864F8, Q864G9, Q864H1, Q864H2, Q864H3, Q864H4, Q864H5, Q864I1, Q864I2, Q864I3, Q864K7

Diamond homologs: B0V1P1, O19037, O77616, O97504, P32244, P32245, P33032, P33033, P34974, P35345, P41149, P41968, P41983, P47798, P55167, P56442, P56443, P56444, P56445, P56446, P56447, P56448, P56450, P56451, P70115, P70596, P79166, Q01718, Q01726, Q01727, Q0Q460, Q0Z8I9, Q29154, Q64326, Q6A155, Q80SS9, Q80SZ5, Q864F4, Q864F5, Q864F6

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
MC2R	“up-regulates quantity”	cortisol
MC2R	“up-regulates activity”	GNAS	binding
ASIP	“down-regulates activity”	MC2R	binding
AGRP	“down-regulates activity”	MC2R	binding
MRAP	“up-regulates activity”	MC2R	binding
MRAP2	“up-regulates activity”	MC2R	binding
POMC	“up-regulates activity”	MC2R	binding
Corticotropin	“up-regulates activity”	MC2R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	12
Uncertain significance	107
Likely benign	18
Benign	25

Top pathogenic / likely-pathogenic (29)

Variant ID	HGVS	Classification
18425	NM_000529.2(MC2R):c.376G>T (p.Ala126Ser)	Pathogenic
279974	NM_000529.2(MC2R):c.579_581del (p.Tyr193_Val194delinsTer)	Pathogenic
3258	NM_000529.2(MC2R):c.221G>T (p.Ser74Ile)	Pathogenic
3260	NM_000529.2(MC2R):c.360C>G (p.Ser120Arg)	Pathogenic
3261	NM_000529.2(MC2R):c.382C>T (p.Arg128Cys)	Pathogenic
3262	NM_000529.2(MC2R):c.319G>A (p.Asp107Asn)	Pathogenic
3263	NM_000529.2(MC2R):c.652_653insA (p.Ala218fs)	Pathogenic
3264	NM_000529.2(MC2R):c.752G>T (p.Cys251Phe)	Pathogenic
3266	NM_000529.2(MC2R):c.761A>G (p.Tyr254Cys)	Pathogenic
3602724	NM_000529.2(MC2R):c.676G>A (p.Gly226Arg)	Pathogenic
444063	NM_000529.2(MC2R):c.702del (p.Phe235fs)	Pathogenic
444064	NM_000529.2(MC2R):c.674T>G (p.Leu225Arg)	Pathogenic
444065	NM_000529.2(MC2R):c.459dup (p.Ile154fs)	Pathogenic
444066	NM_000529.2(MC2R):c.424G>T (p.Val142Leu)	Pathogenic
492865	NM_000529.2(MC2R):c.410G>C (p.Arg137Pro)	Pathogenic
492868	NM_000529.2(MC2R):c.560del (p.Val187fs)	Pathogenic
492869	NM_000529.2(MC2R):c.573C>A (p.Cys191Ter)	Pathogenic
1184898	NM_000529.2(MC2R):c.145G>A (p.Val49Met)	Likely pathogenic
1285296	NM_000529.2(MC2R):c.676G>C (p.Gly226Arg)	Likely pathogenic
2442403	NM_000529.2(MC2R):c.307G>A (p.Asp103Asn)	Likely pathogenic
2498736	NM_000529.2(MC2R):c.817C>T (p.Pro273Ser)	Likely pathogenic
3259	NM_000529.2(MC2R):c.601C>T (p.Arg201Ter)	Likely pathogenic
3377610	NM_000529.2(MC2R):c.548dup (p.Leu184fs)	Likely pathogenic
3775355	NM_000529.2(MC2R):c.434_440del (p.Arg145fs)	Likely pathogenic
3776246	NM_000529.2(MC2R):c.696G>A (p.Trp232Ter)	Likely pathogenic
3903163	NM_000529.2(MC2R):c.357del (p.Phe119fs)	Likely pathogenic
492866	NM_000529.2(MC2R):c.433C>T (p.Arg145Cys)	Likely pathogenic
492867	NM_000529.2(MC2R):c.465G>C (p.Trp155Cys)	Likely pathogenic
492870	NM_000529.2(MC2R):c.634del (p.Arg212fs)	Likely pathogenic

SpliceAI

501 predictions. Top by Δscore:

Variant	Effect	Δscore
18:13885643:TCAC:T	acceptor_gain	0.9900
18:13885644:CAC:C	acceptor_gain	0.9900
18:13885644:CACC:C	acceptor_gain	0.9900
18:13885647:C:CC	acceptor_gain	0.9900
18:13886654:T:TA	donor_gain	0.9900
18:13915483:CTTA:C	donor_loss	0.9900
18:13915484:TTAC:T	donor_loss	0.9900
18:13915485:TAC:T	donor_loss	0.9900
18:13915486:A:AC	donor_gain	0.9900
18:13915487:C:CC	donor_gain	0.9900
18:13885642:ATCAC:A	acceptor_gain	0.9800
18:13915486:AC:A	donor_gain	0.9800
18:13915487:CC:C	donor_gain	0.9800
18:13915487:CCTT:C	donor_gain	0.9800
18:13892606:T:C	acceptor_gain	0.9700
18:13915487:CCT:C	donor_gain	0.9700
18:13885645:AC:A	acceptor_gain	0.9600
18:13885646:CC:C	acceptor_gain	0.9600
18:13915486:ACCTT:A	donor_gain	0.9500
18:13915487:CCTTC:C	donor_gain	0.9500
18:13888665:T:A	donor_gain	0.9200
18:13892161:C:CA	donor_gain	0.9100
18:13915482:ACTT:A	donor_loss	0.9100
18:13885657:G:C	acceptor_gain	0.8900
18:13905340:G:C	donor_gain	0.8700
18:13886633:TA:T	donor_gain	0.8600
18:13884903:T:TA	donor_gain	0.8500
18:13892606:T:TC	acceptor_gain	0.8500
18:13885657:G:GC	acceptor_gain	0.8300
18:13885643:TCACC:T	acceptor_gain	0.8100

AlphaMissense

1983 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:13885324:G:C	S65R	0.998
18:13885324:G:T	S65R	0.998
18:13885326:T:G	S65R	0.998
18:13885159:G:C	S120R	0.997
18:13885159:G:T	S120R	0.997
18:13885161:T:G	S120R	0.997
18:13885297:G:C	S74R	0.996
18:13885297:G:T	S74R	0.996
18:13885299:T:G	S74R	0.996
18:13885056:A:G	W155R	0.993
18:13885056:A:T	W155R	0.993
18:13885173:C:G	G116R	0.992
18:13884828:A:G	C231R	0.991
18:13885136:C:G	R128P	0.991
18:13884818:G:C	P234R	0.990
18:13884825:A:G	W232R	0.990
18:13884825:A:T	W232R	0.990
18:13885407:C:G	G38R	0.988
18:13885407:C:T	G38R	0.988
18:13884818:G:T	P234H	0.987
18:13884835:G:C	F228L	0.987
18:13884835:G:T	F228L	0.987
18:13884837:A:G	F228L	0.987
18:13884826:G:C	C231W	0.986
18:13884843:C:G	G226R	0.986
18:13884843:C:T	G226R	0.986
18:13885047:A:G	C158R	0.986
18:13884695:A:T	I275K	0.985
18:13884827:C:T	C231Y	0.985
18:13885309:A:C	D70E	0.985

dbSNP variants (sampled 300 via entrez): RS1000028974 (18:13881724 G>A), RS1000095477 (18:13910000 G>A), RS1000102815 (18:13892438 G>A), RS1000337555 (18:13890326 T>C), RS1000520784 (18:13895521 G>C), RS1000551760 (18:13895095 G>A), RS1000658379 (18:13916376 C>A,T), RS1000706026 (18:13900214 G>T), RS1000777802 (18:13890126 C>A,G), RS1000788453 (18:13890815 C>T), RS1000915291 (18:13905795 C>T), RS1001071461 (18:13895994 C>T), RS1001088989 (18:13900945 C>T), RS1001104629 (18:13899926 C>T), RS1001136512 (18:13911234 G>A,C)

Disease associations

OMIM: gene MIM:607397 | disease phenotypes: MIM:202200

GenCC curated gene-disease

Disease	Classification	Inheritance
glucocorticoid deficiency 1	Definitive	Autosomal recessive
familial glucocorticoid deficiency	Supportive	Autosomal recessive

Mondo (2): glucocorticoid deficiency 1 (MONDO:0024536), familial glucocorticoid deficiency (MONDO:0008733)

Orphanet (1): Familial glucocorticoid deficiency (Orphanet:361)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000098	Tall stature
HP:0000127	Renal salt wasting
HP:0000826	Precocious puberty
HP:0000846	Adrenal insufficiency
HP:0000851	Congenital hypothyroidism
HP:0000953	Hyperpigmentation of the skin
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001259	Coma
HP:0001325	Hypoglycemic coma
HP:0001508	Failure to thrive
HP:0001639	Hypertrophic cardiomyopathy
HP:0001824	Weight loss
HP:0001988	Recurrent hypoglycemia
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002019	Constipation
HP:0002039	Anorexia
HP:0002153	Hyperkalemia
HP:0002173	Hypoglycemic seizures
HP:0002445	Tetraplegia
HP:0002574	Episodic abdominal pain
HP:0002615	Hypotension
HP:0002719	Recurrent infections
HP:0002902	Hyponatremia
HP:0002960	Autoimmunity

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006697_24	Parental longevity (combined parental attained age, Martingale residuals)	6.000000e-06
GCST006698_5	Parental longevity (both parents in top 10%)	2.000000e-08
GCST007625_5	Negative urgency	9.000000e-07
GCST010266_14	Femoral neck bone mineral density and trunk fat mass adjusted by trunk lean mass	1.000000e-08
GCST010268_7	Femoral neck bone mineral density	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007796	parental longevity
EFO:0006946	behavioural disinhibition measurement
EFO:0007785	femoral neck bone mineral density

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565974	Familial Glucocorticoid Deficiency 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1965 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 30 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL5414447	ATUMELNANT	2	30

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Melanocortin receptors

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
ACTH	Full agonist	9.8	pKd
CRN04894	Antagonist	9.47	pKB
ACTH-(1-24)	Full agonist	9.1	pKd
ACTH-(11-24)	Antagonist	9.0	pKd
ASIP [90-132 (L89Y)]	Inverse agonist	7.3	pIC50

ChEMBL bioactivities

46 potent at pChembl≥5 of 46 total, top 46 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	Ki	0.3	nM	CHEMBL5412684
9.50	Ki	0.3162	nM	CHEMBL5412684
9.50	Ki	0.3162	nM	CHEMBL5435583
9.49	Ki	0.32	nM	CHEMBL5435583
9.41	Ki	0.39	nM	CHEMBL5432648
9.40	Ki	0.3981	nM	CHEMBL5432648
9.40	Ki	0.3981	nM	CHEMBL5414709
9.40	Ki	0.4	nM	CHEMBL5414709
9.33	Ki	0.47	nM	CHEMBL5414552
9.30	Ki	0.5012	nM	CHEMBL5414552
9.20	Ki	0.631	nM	CHEMBL5396357
9.20	Ki	0.63	nM	CHEMBL5396357
9.05	Ki	0.9	nM	CHEMBL5417272
9.02	Ki	0.96	nM	CHEMBL5424729
9.00	Ki	1	nM	CHEMBL5424729
9.00	Ki	1	nM	CHEMBL5417272
8.96	Ki	1.1	nM	CHEMBL5394322
8.90	Ki	1.259	nM	CHEMBL5394322
8.90	Ki	1.259	nM	CHEMBL5406402
8.89	Ki	1.3	nM	CHEMBL5406402
8.82	Ki	1.5	nM	CHEMBL5415832
8.80	Ki	1.585	nM	CHEMBL5401503
8.80	Ki	1.6	nM	CHEMBL5401503
8.80	Ki	1.585	nM	CHEMBL5415832
8.80	Ki	1.585	nM	CHEMBL5438739
8.80	Ki	1.6	nM	CHEMBL5438739
8.70	Ki	1.995	nM	CHEMBL5421498
8.70	Ki	2	nM	CHEMBL5421498
8.70	Ki	1.995	nM	ATUMELNANT
8.68	Ki	2.1	nM	ATUMELNANT
8.52	Ki	3	nM	CHEMBL5403170
8.50	Ki	3.162	nM	CHEMBL5403170
8.43	Ki	3.7	nM	CHEMBL5422885
8.40	Ki	3.981	nM	CHEMBL5422885
8.40	Ki	3.981	nM	CHEMBL5397644
8.36	Ki	4.4	nM	CHEMBL5397644
8.32	Ki	4.8	nM	CHEMBL5405192
8.30	Ki	5.012	nM	CHEMBL5405192
7.70	Ki	19.95	nM	CHEMBL5435301
7.68	Ki	21	nM	CHEMBL5435301
7.60	Ki	25.12	nM	CHEMBL5396826
7.60	Ki	25	nM	CHEMBL5396826
7.44	Ki	36	nM	CHEMBL5434090
7.40	Ki	39.81	nM	CHEMBL5434090
7.33	Ki	47	nM	CHEMBL5438731
7.30	Ki	50.12	nM	CHEMBL5438731

PubChem BioAssay actives

46 with measured affinity, of 112 total; 23 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[(2R)-4-[4-chloro-2-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]-6-(2-ethoxy-3-pyridinyl)-N-[(3R)-1-methylpyrrolidin-3-yl]pyridine-2-carboxamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0003	uM
3-[(2R)-4-[4-chloro-2-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]-6-(2-ethoxy-3-pyridinyl)-N-[(3R)-pyrrolidin-3-yl]pyridine-2-carboxamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0003	uM
3-[(2R)-4-[4-chloro-2-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]-N-[2-(dimethylamino)ethyl]-6-(2-ethoxy-3-pyridinyl)pyridine-2-carboxamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0004	uM
6-(2-ethoxy-3-pyridinyl)-3-[(2R)-2-ethyl-4-[4-(trifluoromethyl)bicyclo[2.2.2]octane-1-carbonyl]piperazin-1-yl]-N-[(3R)-1-methylpyrrolidin-3-yl]pyridine-2-carboxamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0004	uM
3-[(2R)-4-[4-chloro-2-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]-6-(2-ethoxy-3-pyridinyl)-N-[2-(methylamino)ethyl]pyridine-2-carboxamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0005	uM
6-(2-ethoxy-3-pyridinyl)-3-[(2R)-2-ethyl-4-[1-(trifluoromethyl)cyclopentanecarbonyl]piperazin-1-yl]-N-[(3R)-1-methylpyrrolidin-3-yl]pyridine-2-carboxamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0006	uM
6-[(2R)-4-[4-chloro-2-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]-N-[2-(dimethylamino)ethyl]-3-(2-ethoxy-3-pyridinyl)-2-fluorobenzamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0009	uM
2-[(2R)-4-[4-chloro-2-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]-5-(2-ethoxy-3-pyridinyl)-N-[2-(methylamino)ethyl]benzamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0010	uM
N-(2-aminoethyl)-2-[(2R)-4-[4-chloro-2-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]-5-(2-ethoxy-3-pyridinyl)benzamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0011	uM
6-(2-ethoxyphenyl)-3-[(2R)-2-ethyl-4-[1-(trifluoromethyl)cyclobutanecarbonyl]piperazin-1-yl]-N-[(3R)-1-methylpyrrolidin-3-yl]pyridine-2-carboxamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0013	uM
2-[(2R)-4-[4-chloro-2-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]-N-[2-(dimethylamino)ethyl]-5-(2-ethoxy-3-pyridinyl)benzamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0015	uM
N-(2-aminoethyl)-2-[(2R)-4-[4-chloro-2-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]-5-(2-ethoxyphenyl)benzamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0016	uM
6-(2-ethoxyphenyl)-3-[(2R)-2-ethyl-4-[1-(trifluoromethyl)cyclobutanecarbonyl]piperazin-1-yl]-N-(1-methylpiperidin-4-yl)pyridine-2-carboxamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0016	uM
N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-6-(2-ethoxyphenyl)-3-[(2R)-2-ethyl-4-[1-(trifluoromethyl)cyclobutanecarbonyl]piperazin-1-yl]pyridine-2-carboxamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0020	uM
N-(2-aminoethyl)-2-[(2R)-4-[2-chloro-4-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]-5-(2-ethoxyphenyl)benzamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0020	uM
6-(2-ethoxy-3-pyridinyl)-3-[(2R)-2-ethyl-4-[1-(trifluoromethyl)cyclobutanecarbonyl]piperazin-1-yl]-N-(1-methylpiperidin-4-yl)pyridine-2-carboxamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0030	uM
6-(2-ethoxy-3-pyridinyl)-3-[(2R)-2-ethyl-4-[1-(trifluoromethyl)cyclobutanecarbonyl]piperazin-1-yl]-N-[(3R)-1-methylpyrrolidin-3-yl]pyridine-2-carboxamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0037	uM
N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-6-(2-ethoxy-3-pyridinyl)-3-[(2R)-2-ethyl-4-[1-(trifluoromethyl)cyclobutanecarbonyl]piperazin-1-yl]pyridine-2-carboxamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0040	uM
N-(2-aminoethyl)-2-[(2R)-4-(2,4-dichlorobenzoyl)-2-ethylpiperazin-1-yl]-5-(2-ethoxyphenyl)benzamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0048	uM
N-(2-aminoethyl)-5-(2-chlorophenyl)-2-[(2R)-4-[2-chloro-4-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]benzamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0199	uM
N-(2-aminoethyl)-2-[(2R)-4-[2-chloro-4-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]-5-(2-cyanophenyl)benzamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0250	uM
N-(2-aminoethyl)-5-(2-chloro-3-fluorophenyl)-2-[(2R)-4-[2-chloro-4-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]benzamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0360	uM
N-(2-aminoethyl)-2-[(2R)-4-[2-chloro-4-(trifluoromethyl)benzoyl]-2-ethylpiperazin-1-yl]-5-(2-fluorophenyl)benzamide	1993795: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method	ki	0.0470	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Colforsin	increases expression, decreases reaction	2
methylmercuric chloride	increases expression, affects cotreatment	1
alternariol	increases expression	1
bisphenol A	decreases methylation	1
tributyltin	affects cotreatment, increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects cotreatment, increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression, affects cotreatment	1
acetyl methyl tetramethyl tetralin	affects cotreatment, decreases expression, increases expression	1
naphthenic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression, affects cotreatment	1
hexabromocyclododecane	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
enniatins	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	affects cotreatment, increases expression	1
Lamotrigine	increases response to substance	1
Arsenic Trioxide	increases expression	1
Cyclic AMP	affects cotreatment, decreases expression	1
Asbestos	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Environmental Pollutants	increases expression	1
Mycotoxins	increases expression	1
Tamoxifen	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Valproic Acid	decreases reaction, increases expression	1
Water Pollutants, Chemical	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, decreases expression	1

ChEMBL screening assays

12 unique, capped per target: 7 functional, 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3377682	Binding	Agonist activity at human MC2 receptor at 100 uM to 5 mM	Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor. — Bioorg Med Chem
CHEMBL5320117	Functional	Agonist activity at human MC2R expressed in CHO cells assessed as increase in alpha-MSH induced cAMP level measured for 60 mins	Discovery of the Potent and Selective MC4R Antagonist PF-07258669 for the Potential Treatment of Appetite Loss. — J Med Chem

Cellosaurus cell lines

4 cell lines: 2 spontaneously immortalized cell line, 1 induced pluripotent stem cell, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4XL	SDQLCHi029-A	Induced pluripotent stem cell	Female
CVCL_B1WV	Abcam HeLa MC2R KO	Cancer cell line	Female
CVCL_H459	CHO-K1/MC2/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KS01	GeneBLAzer MC2R-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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