MRAP

melanocortin 2 receptor accessory protein

Basic information

Region (hg38): 21:32291813-32314784

Previous symbols: [ "C21orf61" ]

Links

ENSG00000170262 ∙ NCBI:56246 ∙ OMIM:609196 ∙ HGNC:1304 ∙ Uniprot:Q8TCY5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glucocorticoid deficiency 2 (Strong), mode of inheritance: AR
• familial glucocorticoid deficiency (Supportive), mode of inheritance: AR
• glucocorticoid deficiency 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glucocorticoid deficiency 2	AR	Endocrine	Cortisol treatment can be effective to pevent manifestations such as hypoglycemia or severe sequelae of infectious episodes in infancy/childhood	Endocrine	15654338; 16868047; 20427498; 21951701

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MRAP gene.

• Inborn_genetic_diseases (29 variants)
• Glucocorticoid_deficiency_2 (23 variants)
• not_provided (10 variants)
• MRAP-related_disorder (4 variants)
• Glucocorticoid_deficiency_1 (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MRAP gene is commonly pathogenic or not. These statistics are base on transcript: NM_001379228.1. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	4	3	10
missense			28	5	2	35
nonsense						0
start loss	2					2
frameshift	1		2			3
splice donor/acceptor (+/-2bp)	4					4
Total	7	0	33	9	5

Highest pathogenic variant AF is 0.0000830539

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MRAP	protein_coding	protein_coding	ENST00000399784	3	22972

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00208	0.525	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0747	103	101	1.02	0.00000580	1113
Missense in Polyphen		31	25.77	1.203		314
Synonymous	-1.16	58	47.8	1.21	0.00000334	350
Loss of Function	0.176	4	4.40	0.909	2.87e-7	44

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000149	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00106	0.00106
European (Non-Finnish)	0.000132	0.000132
Middle Eastern	0.000109	0.000109
South Asian	0.0000982	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: 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 adrenal cells and for signaling in response to corticotropin (ACTH). May be involved in the intracellular trafficking pathways in adipocyte cells. {ECO:0000269|PubMed:15654338, ECO:0000269|PubMed:19329486, ECO:0000269|PubMed:20371771}.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.357

Intolerance Scores

• loftool: 0.348
• rvis_EVS: 0.37
• rvis_percentile_EVS: 75.29

Haploinsufficiency Scores

• pHI: 0.164
• hipred: N
• hipred_score: 0.146
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.313

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mrap

Gene ontology

• Biological process: protein localization to plasma membrane;positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway;negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway;negative regulation of protein localization to plasma membrane
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;integral component of membrane
• Molecular function: protein binding;corticotropin hormone receptor binding;type 3 melanocortin receptor binding;type 4 melanocortin receptor binding;type 5 melanocortin receptor binding;identical protein binding;type 1 melanocortin receptor binding