HCAR2

hydroxycarboxylic acid receptor 2, the group of Hydroxycarboxylic acid receptors

Basic information

Region (hg38): 12:122701293-122703357

Previous symbols: [ "GPR109A" ]

Links

ENSG00000182782 ∙ NCBI:338442 ∙ OMIM:609163 ∙ HGNC:24827 ∙ Uniprot:Q8TDS4 ∙ 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 HCAR2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HCAR2 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						0
missense			34		1	35
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	34	0	1

Variants in HCAR2

This is a list of pathogenic ClinVar variants found in the HCAR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-122702218-A-T		not specified	Uncertain significance (May 15, 2023)
12-122702222-G-T		not specified	Uncertain significance (Jun 29, 2022)
12-122702311-G-A		not specified	Uncertain significance (Aug 13, 2021)
12-122702324-C-A		not specified	Uncertain significance (Mar 06, 2023)
12-122702333-C-T			Benign (Jul 13, 2018)
12-122702372-G-T		not specified	Uncertain significance (Aug 01, 2024)
12-122702380-G-A		not specified	Uncertain significance (Jul 14, 2024)
12-122702410-C-T		not specified	Uncertain significance (Jul 09, 2021)
12-122702413-G-A		not specified	Uncertain significance (Nov 02, 2023)
12-122702472-G-A		not specified	Uncertain significance (Apr 27, 2022)
12-122702496-G-A		not specified	Uncertain significance (Mar 28, 2024)
12-122702506-T-G		not specified	Uncertain significance (Jan 21, 2025)
12-122702532-C-T		not specified	Uncertain significance (Sep 20, 2023)
12-122702554-A-G		not specified	Uncertain significance (Mar 24, 2023)
12-122702563-C-T		not specified	Likely benign (Jan 09, 2025)
12-122702569-C-T		not specified	Uncertain significance (Aug 17, 2021)
12-122702609-C-A		not specified	Uncertain significance (Nov 09, 2023)
12-122702638-G-A		not specified	Uncertain significance (Nov 26, 2024)
12-122702720-C-G		not specified	Uncertain significance (Dec 17, 2024)
12-122702728-A-G		not specified	Uncertain significance (Dec 03, 2024)
12-122702728-A-T		not specified	Uncertain significance (Mar 28, 2024)
12-122702730-G-A		not specified	Uncertain significance (Jul 12, 2022)
12-122702767-C-A		not specified	Uncertain significance (Sep 16, 2021)
12-122702806-C-T		not specified	Uncertain significance (Nov 06, 2023)
12-122702820-G-A		not specified	Uncertain significance (Dec 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HCAR2	protein_coding	protein_coding	ENST00000328880	1	2051

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000189	0.490	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.204	221	213	1.04	0.0000136	2399
Missense in Polyphen		44	60.005	0.73327		775
Synonymous	-0.787	97	87.6	1.11	0.00000570	727
Loss of Function	0.349	6	7.00	0.858	3.91e-7	71

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a high affinity receptor for both nicotinic acid (also known as niacin) and (D)-beta-hydroxybutyrate and mediates increased adiponectin secretion and decreased lipolysis through G(i)-protein-mediated inhibition of adenylyl cyclase. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Mediates nicotinic acid-induced apoptosis in mature neutrophils. Receptor activation by nicotinic acid results in reduced cAMP levels which may affect activity of cAMP-dependent protein kinase A and phosphorylation of target proteins, leading to neutrophil apoptosis. The rank order of potency for the displacement of nicotinic acid binding is 5- methyl pyrazole-3-carboxylic acid = pyridine-3-acetic acid > acifran > 5-methyl nicotinic acid = acipimox >> nicotinuric acid = nicotinamide. {ECO:0000269|PubMed:17932499}.
• Pathway: cAMP signaling pathway - Homo sapiens (human);Signaling by GPCR;Signal Transduction;Hydroxycarboxylic acid-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Intolerance Scores

• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.54

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.187
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hcar2
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: neutrophil apoptotic process;G protein-coupled receptor signaling pathway;positive regulation of neutrophil apoptotic process;negative regulation of lipid catabolic process;positive regulation of adiponectin secretion
• Cellular component: plasma membrane;integral component of membrane;cell junction
• Molecular function: nicotinic acid receptor activity