MRAP2

melanocortin 2 receptor accessory protein 2

Basic information

Region (hg38): 6:84033772-84090881

Previous symbols: [ "C6orf117" ]

Links

ENSG00000135324 ∙ NCBI:112609 ∙ OMIM:615410 ∙ HGNC:21232 ∙ Uniprot:Q96G30 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Obesity, susceptibility to, 18	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Endocrine	23869016

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MRAP2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MRAP2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	2	7
missense			18	2		20
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			3	1	1	5
non coding			1	2	2	5
Total	0	0	22	9	4

Variants in MRAP2

This is a list of pathogenic ClinVar variants found in the MRAP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-84055314-C-T		MRAP2-related disorder	Likely benign (May 02, 2022)
6-84055325-G-A		MRAP2-related disorder	Uncertain significance (Jan 20, 2024)
6-84055336-A-C		MRAP2-related disorder	Uncertain significance (Jul 10, 2024)
6-84055345-C-T		MRAP2-related disorder	Likely benign (Sep 04, 2024)
6-84055346-A-G			Uncertain significance (Jun 01, 2024)
6-84055354-C-A		MRAP2-related disorder	Likely benign (Aug 27, 2023)
6-84055360-A-G		MRAP2-related disorder	Likely benign (Oct 31, 2022)
6-84055362-C-T		not specified	Uncertain significance (Aug 30, 2023)
6-84055376-G-C		not specified • MRAP2-related disorder	Uncertain significance (Sep 22, 2023)
6-84055382-A-G		MRAP2-related disorder	Uncertain significance (Aug 10, 2023)
6-84055387-G-A		MRAP2-related disorder	Uncertain significance (Mar 04, 2024)
6-84055388-G-T		Body mass index quantitative trait locus 18	risk factor (Jul 19, 2013)
6-84055396-A-G		MRAP2-related disorder	Likely benign (Dec 15, 2023)
6-84055399-T-G			Uncertain significance (May 05, 2023)
6-84055413-C-T		MRAP2-related disorder	Uncertain significance (Aug 10, 2024)
6-84055427-G-A		not specified	Uncertain significance (Jun 17, 2022)
6-84055432-GA-G		MRAP2-related disorder	Uncertain significance (Dec 19, 2023)
6-84055436-G-T		MRAP2-related disorder	Uncertain significance (Apr 30, 2024)
6-84055440-A-C		MRAP2-related disorder	Uncertain significance (Nov 27, 2023)
6-84055450-G-T		MRAP2-related disorder	Uncertain significance (Aug 14, 2023)
6-84055452-T-G		MRAP2-related disorder	Benign (Jan 31, 2024)
6-84055455-A-G		MRAP2-related disorder	Likely benign (Mar 14, 2023)
6-84062885-T-C		MRAP2-related disorder	Uncertain significance (Apr 03, 2024)
6-84062886-C-G		MRAP2-related disorder	Likely benign (Sep 21, 2023)
6-84062888-T-G		MRAP2-related disorder	Likely benign (Sep 02, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MRAP2	protein_coding	protein_coding	ENST00000257776	3	57126

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.56e-7	0.0906	125717	0	30	125747	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.309	99	108	0.916	0.00000520	1355
Missense in Polyphen		38	36.723	1.0348		490
Synonymous	-0.249	44	42.0	1.05	0.00000221	389
Loss of Function	-0.670	9	7.08	1.27	2.95e-7	96

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000490	0.000490
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000543	0.0000527
Middle Eastern	0.0000544	0.0000544
South Asian	0.000198	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Modulator of melanocortin receptor 4 (MC4R), a receptor involved in energy homeostasis. Plays a central role in the control of energy homeostasis and body weight regulation by increasing ligand-sensitivity of MC4R and MC4R-mediated generation of cAMP (By similarity). May also act as a negative regulator of MC2R: competes with MRAP for binding to MC2R and impairs the binding of corticotropin (ACTH) to MC2R. May also regulate activity of other melanocortin receptors (MC1R, MC3R and MC5R); however, additional evidences are required in vivo. {ECO:0000250, ECO:0000269|PubMed:19329486, ECO:0000269|PubMed:20371771}.
• Disease: DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:23869016}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.352
• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

• pHI: 0.184
• hipred: N
• hipred_score: 0.334
• ghis: 0.546

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.261

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mrap2
• Phenotype: homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; skeleton phenotype; immune system phenotype; digestive/alimentary phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype

Zebrafish Information Network

• Gene name: mrap2a
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: energy reserve metabolic process;feeding behavior;regulation of signaling receptor activity;protein localization to plasma membrane;energy homeostasis;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;receptor regulator activity;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