MRAP (melanocortin 2 receptor accessory protein)

Gene

• Entrez ID: 56246
• Gene name: Melanocortin 2 receptor accessory protein
• Gene symbol: MRAP
• Synonyms (NCBI Gene): B27, C21orf61, FALP, FGD2, GCCD2, MRAP1
• Chromosome: 21
• Chromosome location: 21q22.11
• Summary: This gene encodes a melanocortin receptor-interacting protein. The encoded protein regulates trafficking and function of the melanocortin 2 receptor in the adrenal gland. The encoded protein can also modulate signaling of other melanocortin receptors. Mut

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs80358231	G>A	Pathogenic	Missense variant, initiator codon variant, intron variant
rs566223651	G>A,C,T	Pathogenic	Splice donor variant, intron variant
rs1476574441	G>-	Pathogenic	Intron variant, splice donor variant
rs1555897462	A>G	Pathogenic	Intron variant, initiator codon variant, missense variant
rs1569025178	ACGCCTC>-	Pathogenic	Intron variant, frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1157562	hsa-miR-299-3p	CLIP-seq
MIRT1157563	hsa-miR-3144-5p	CLIP-seq
MIRT1157564	hsa-miR-3151	CLIP-seq
MIRT1157565	hsa-miR-3191	CLIP-seq
MIRT1157566	hsa-miR-4447	CLIP-seq
MIRT1157567	hsa-miR-4472	CLIP-seq
MIRT1157568	hsa-miR-4652-5p	CLIP-seq
MIRT1157569	hsa-miR-4717-5p	CLIP-seq
MIRT1157570	hsa-miR-491-5p	CLIP-seq
MIRT1157571	hsa-miR-645	CLIP-seq
MIRT2274290	hsa-miR-3545-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	18077336, 18840636, 19151134, 19329486, 20371771, 28298427, 32814053
GO:0005783	Component	Endoplasmic reticulum	IBA
GO:0005783	Component	Endoplasmic reticulum	IDA	19329486
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	19329486
GO:0005886	Component	Plasma membrane	IEA
GO:0016020	Component	Membrane	IEA
GO:0030545	Function	Signaling receptor regulator activity	IBA
GO:0031780	Function	Corticotropin hormone receptor binding	IBA
GO:0031780	Function	Corticotropin hormone receptor binding	IPI	19329486
GO:0031781	Function	Type 3 melanocortin receptor binding	IBA
GO:0031781	Function	Type 3 melanocortin receptor binding	IPI	19329486
GO:0031782	Function	Type 4 melanocortin receptor binding	IBA
GO:0031782	Function	Type 4 melanocortin receptor binding	IPI	19329486
GO:0031783	Function	Type 5 melanocortin receptor binding	IBA
GO:0031783	Function	Type 5 melanocortin receptor binding	IPI	19329486
GO:0042802	Function	Identical protein binding	IPI	18077336, 20371771
GO:0070996	Function	Type 1 melanocortin receptor binding	IBA
GO:0070996	Function	Type 1 melanocortin receptor binding	IPI	19329486
GO:0072659	Process	Protein localization to plasma membrane	IBA
GO:0072659	Process	Protein localization to plasma membrane	IDA	19329486
GO:0106070	Process	Regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA
GO:0106071	Process	Positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA	19329486
GO:0106072	Process	Negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA	19329486
GO:1903077	Process	Negative regulation of protein localization to plasma membrane	IDA	19329486

Other IDs

• MIM: 609196
• HGNC: 1304
• e!Ensembl: ENSG00000170262

Protein

• UniProt ID: Q8TCY5
• Protein name: Melanocortin-2 receptor accessory protein (B27) (Fat cell-specific low molecular weight protein) (Fat tissue-specific low MW protein)
• Protein function: Modulator of melanocortin receptors (MC1R, MC2R, MC3R, MC4R and MC5R). Acts by increasing ligand-sensitivity of melanocortin receptors and enhancing generation of cAMP by the receptors. Required both for MC2R trafficking to the cell surface of a
• PDB: 8GY7
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF15183	MRAP	1 → 89	Melanocortin-2 receptor accessory protein family	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in adrenal cortex, testis, breast, thyroid, lymph node, ovary and fat. Expressed in adipose tissues. {ECO:0000269|PubMed:15654338}.
• Sequence:

  MANGTNASAPYYSYEYYLDYLDLIPVDEKKLKAHKHSIVIAFWVSLAAFVVLLFLILLYM
  SWSASPQMRNSPKHHQTCPWSHGLNLHLCIQKCLPCHREPLATSQAQASSVEPGSRTGPD
  QPLRQESSSTLPLGGFQTHPTLLWELTLNGGPLVRSKPSEPPPGDRTSQLQS

• Sequence length: 172

Pathways

KEGG:

Cortisol synthesis and secretion
Cushing syndrome

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Glucocorticoid deficiency 1	Pathogenic	rs80358231, rs1555897462, rs1476574441	RCV000513053 RCV000512739 RCV000513343	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Glucocorticoid deficiency 2	Pathogenic	rs566223651, rs2516869613, rs80358231, rs1569025178, rs1476574441	RCV000001910 RCV000001911 RCV000001912 RCV000001914 RCV000001915 RCV000001917 RCV002250648	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MRAP-related disorder	Likely pathogenic	rs1064796398	RCV003409666	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ATRIAL FIBRILLATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL GLUCOCORTICOID DEFICIENCY	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL GLUCOCORTICOID DEFICIENCY TYPE 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL GLUCOCORTICOID DEFICIENCY TYPE 2	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Glucocorticoid Deficiency	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Aarskog syndrome	Aarskog Syndrome	BEFREE	16868047, 18426811, 19558534, 19903795, 21274326, 21701219, 23708259, 31189126		★☆☆☆☆ Found in Text Mining only
Anemia Hemolytic	Hemolytic anemia	Pubtator	15282673	Associate	★☆☆☆☆ Found in Text Mining only
Ankylosing spondylitis	Ankylosing Spondylitis	BEFREE	10027781, 12826378, 16755659, 17472990, 20652381, 22881057, 23524147, 23620109, 23767933, 24261772, 26458738, 27909141, 3042071, 608274, 6418260, 8112024		★☆☆☆☆ Found in Text Mining only
Anorexia	Anorexia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	Pubtator	11352256, 23804219, 7763114	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	Pubtator	2111123, 3878147	Stimulate	★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	BEFREE	21459940, 2672931, 886557		★☆☆☆☆ Found in Text Mining only
Arthritis Juvenile	Juvenile arthritis	Pubtator	10446870, 10513798, 36574181	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Psoriatic	Psoriatic arthritis	Pubtator	22006066	Stimulate	★☆☆☆☆ Found in Text Mining only
Arthritis Reactive	Reactive arthritis	Pubtator	15248225, 16107515, 2879815, 702543	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Reactive	Reactive arthritis	Pubtator	3878147	Inhibit	★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	10446870	Associate	★☆☆☆☆ Found in Text Mining only
Azoospermia	Azoospermia	HPO_DG			★☆☆☆☆ Found in Text Mining only
beta Thalassemia	Beta thalassemia	Pubtator	3666141, 3955238, 7173395	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Hypothyroidism	Congenital Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial glucocorticoid deficiency	Glucocorticoid Deficiency	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial glucocorticoid deficiency	Glucocorticoid Deficiency	BEFREE	16868047, 17466001, 19558534		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Glucocorticoid Deficiency 1	Glucocorticoid deficiency	Pubtator	21274326	Associate	★☆☆☆☆ Found in Text Mining only
Familial Glucocorticoid Deficiency Type 1	Glucocorticoid Deficiency	ORPHANET_DG	15654338, 17893271, 20427498		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Glucocorticoid Deficiency Type 1	Glucocorticoid Deficiency	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Glucocorticoid Deficiency Type 2	Glucocorticoid Deficiency	CLINVAR_DG	15654338		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Glucocorticoid Deficiency Type 2	Glucocorticoid Deficiency	BEFREE	20427498		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Glucocorticoid Deficiency Type 2	Glucocorticoid Deficiency	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Glucocorticoid Deficiency Type 2	Glucocorticoid Deficiency	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Glucocorticoid Deficiency 2	Glucocorticoid deficiency	Pubtator	19558534, 19773404, 21274326	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Glucocorticoid deficiency with achalasia	Glucocorticoid Deficiency With Achalasia	BEFREE	17466001, 18426811		★☆☆☆☆ Found in Text Mining only
Hyperaldosteronism	Hyperaldosteronism	Pubtator	33796077	Associate	★☆☆☆☆ Found in Text Mining only
Hypernatriuria	Hypernatriuria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertrophic Cardiomyopathy	Hypertrophic cardiomyopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoglycemic coma	Hypoglycemic coma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoglycemic seizures	Hypoglycemic seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory bowel disease	Pubtator	107868	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney disease	Pubtator	16705817	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple sclerosis	Pubtator	2351974	Stimulate	★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	17609824	Associate	★☆☆☆☆ Found in Text Mining only
Precocious Puberty	Precocious puberty	HPO_DG			★☆☆☆☆ Found in Text Mining only
Psoriasis	Psoriasis	Pubtator	107868	Associate	★☆☆☆☆ Found in Text Mining only
Quadriplegia	Quadriplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spondylarthritis	Spondyloarthritis	BEFREE	29849482		★☆☆☆☆ Found in Text Mining only
Spondylitis Ankylosing	Ankylosing spondylitis	Pubtator	102477, 12746911, 15624199, 16200602, 16385505, 16805919, 18036353, 22576154, 26841353, 2879815, 31212633, 34518303, 6171370, 6191893, 702543, 7688791, 7763114, 8112024	Associate	★☆☆☆☆ Found in Text Mining only
Spondylitis Ankylosing	Ankylosing spondylitis	Pubtator	3878147, 409732	Stimulate	★☆☆☆☆ Found in Text Mining only
Testicular adrenal rest tumor	Testicular adrenal rest tumor	HPO_DG			★☆☆☆☆ Found in Text Mining only
Uveitis	Uveitis	BEFREE	28245629		★☆☆☆☆ Found in Text Mining only
Uveitis	Uveitis	Pubtator	34783307, 36574181	Associate	★☆☆☆☆ Found in Text Mining only
Uveitis Anterior	Anterior uveitis	Pubtator	7763114, 9306872	Associate	★☆☆☆☆ Found in Text Mining only
X-linked Adrenal Hypoplasia	Adrenal Hypoplasia, X-Linked	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only