RARRES2

retinoic acid receptor responder 2, the group of Receptor ligands

Basic information

Region (hg38): 7:150338316-150341662

Links

ENSG00000106538 ∙ NCBI:5919 ∙ OMIM:601973 ∙ HGNC:9868 ∙ Uniprot:Q99969 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RARRES2 gene.

• Inborn genetic diseases (6 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RARRES2 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					1	1
missense			5	1		6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	5	1	1

Variants in RARRES2

This is a list of pathogenic ClinVar variants found in the RARRES2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-150338698-C-T		not specified	Uncertain significance (Apr 19, 2023)
7-150338988-G-T			Benign (Aug 16, 2018)
7-150339023-C-T		not specified	Uncertain significance (Jun 30, 2022)
7-150340146-C-T		not specified	Uncertain significance (Jan 07, 2022)
7-150340155-G-A		not specified	Uncertain significance (Jan 04, 2022)
7-150340477-A-T		not specified	Uncertain significance (Jul 14, 2023)
7-150340519-G-T		not specified	Uncertain significance (Jan 30, 2024)
7-150340550-G-C			Benign (Jul 06, 2018)
7-150340602-C-T		not specified	Likely benign (Oct 29, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RARRES2	protein_coding	protein_coding	ENST00000466675	4	3356

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000272	0.335	125727	0	17	125744	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.385	80	90.3	0.886	0.00000492	1017
Missense in Polyphen		26	26.059	0.99775		354
Synonymous	1.94	22	37.0	0.595	0.00000177	324
Loss of Function	0.0786	7	7.23	0.968	3.09e-7	82

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000219	0.000219
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000675	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adipocyte-secreted protein (adipokine) that regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1). Its other ligands include G protein-coupled receptor 1 (GPR1) and chemokine receptor-like 2 (CCRL2). Positively regulates adipocyte differentiation, modulates the expression of adipocyte genes involved in lipid and glucose metabolism and might play a role in angiogenesis, a process essential for the expansion of white adipose tissue. Also acts as a proinflammatory adipokine, causing an increase in secretion of proinflammatory and prodiabetic adipokines, which further impair adipose tissue metabolic function and have negative systemic effects including impaired insulin sensitivity, altered glucose and lipid metabolism, and a decrease in vascular function in other tissues. Can have both pro- and anti-inflammatory properties depending on the modality of enzymatic cleavage by different classes of proteases. Acts as a chemotactic factor for leukocyte populations expressing CMKLR1, particularly immature plasmacytoid dendritic cells, but also immature myeloid DCs, macrophages and natural killer cells. Exerts an anti-inflammatory role by preventing TNF/TNFA-induced VCAM1 expression and monocytes adhesion in vascular endothelial cells. The effect is mediated via inhibiting activation of NF-kappa-B and CRK/p38 through stimulation of AKT1/NOS3 signaling and nitric oxide production. Its dual role in inflammation and metabolism might provide a link between chronic inflammation and obesity, as well as obesity- related disorders such as type 2 diabetes and cardiovascular disease. Exhibits an antimicrobial function in the skin. {ECO:0000269|PubMed:14675762, ECO:0000269|PubMed:17635925, ECO:0000269|PubMed:17767914, ECO:0000269|PubMed:18242188, ECO:0000269|PubMed:20237162, ECO:0000269|PubMed:22634313, ECO:0000269|PubMed:23527010}.
• Pathway: Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.119

Intolerance Scores

• loftool: 0.503
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.19

Haploinsufficiency Scores

• pHI: 0.305
• hipred: N
• hipred_score: 0.180
• ghis: 0.516

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.122

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rarres2
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; endocrine/exocrine gland phenotype; immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: retinoid metabolic process;in utero embryonic development;positive regulation of protein phosphorylation;platelet degranulation;chemotaxis;inflammatory response;insulin receptor signaling pathway;positive regulation of macrophage chemotaxis;antifungal humoral response;cell differentiation;innate immune response;positive regulation of fat cell differentiation;embryonic digestive tract development;defense response to Gram-negative bacterium;defense response to Gram-positive bacterium;positive regulation of chemotaxis;regulation of lipid catabolic process;antifungal innate immune response
• Cellular component: extracellular region;extracellular space;extracellular matrix;platelet dense granule lumen
• Molecular function: signaling receptor binding;protein binding