HTR2C

5-hydroxytryptamine receptor 2C, the group of 5-hydroxytryptamine receptors, G protein-coupled|Small nucleolar RNA protein coding host genes|MicroRNA protein coding host genes

Basic information

Region (hg38): X:114584077-114910061

Previous symbols: [ "HTR1C" ]

Links

ENSG00000147246 ∙ NCBI:3358 ∙ OMIM:312861 ∙ HGNC:5295 ∙ Uniprot:P28335 ∙ 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 HTR2C gene.

• Inborn genetic diseases (12 variants)
• not provided (5 variants)
• HTR2C-related condition (5 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HTR2C 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			2	1		3
missense			13	3		16
nonsense						0
start loss						0
frameshift		1				1
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	1	15	4	2

Variants in HTR2C

This is a list of pathogenic ClinVar variants found in the HTR2C region.

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

Position	Type	Phenotype	Significance	ClinVar
X-114584109-C-C			Benign (Mar 13, 2018)
X-114726930-A-T		HTR2C-related disorder	Likely benign (Jul 06, 2023)
X-114726944-A-G		HTR2C-related disorder	Uncertain significance (Nov 20, 2023)
X-114726956-C-T		HTR2C-related disorder	Likely benign (Feb 07, 2022)
X-114726957-G-A		HTR2C-related disorder	Likely benign (Jan 11, 2023)
X-114726960-G-A		HTR2C-related disorder	Uncertain significance (Mar 28, 2023)
X-114731301-C-T		HTR2C-related disorder	Likely benign (Nov 09, 2022)
X-114731303-A-G		HTR2C-related disorder	Likely benign (Aug 30, 2023)
X-114731326-C-C		SEROTONIN 5-HT-2C RECEPTOR POLYMORPHISM • HTR2C-related disorder	Benign (Aug 19, 2022)
X-114731342-C-T		HTR2C-related disorder	Likely benign (Dec 15, 2022)
X-114731350-C-T		HTR2C-related disorder	Uncertain significance (Dec 19, 2022)
X-114731382-G-C		HTR2C-related disorder	Likely benign (Sep 13, 2021)
X-114731430-C-T		HTR2C-related disorder	Uncertain significance (Feb 19, 2024)
X-114731436-A-G		HTR2C-related disorder	Uncertain significance (Dec 22, 2023)
X-114731439-G-A		HTR2C-related disorder	Uncertain significance (Jan 31, 2024)
X-114731461-T-C		not specified	Uncertain significance (Apr 12, 2023)
X-114848019-A-G		HTR2C-related disorder	Likely benign (Nov 16, 2022)
X-114848083-C-A		not specified	Uncertain significance (Oct 17, 2023)
X-114848155-C-T		Malignant tumor of prostate	Uncertain significance (-)
X-114848165-C-T		HTR2C-related disorder	Likely benign (Jun 25, 2021)
X-114903581-C-G		not specified	Benign (Mar 09, 2018)
X-114906591-G-A		not specified	Uncertain significance (Mar 27, 2023)
X-114906602-T-C		HTR2C-related disorder	Likely benign (Mar 14, 2022)
X-114906698-C-T		HTR2C-related disorder	Likely benign (Nov 17, 2023)
X-114906816-A-G		HTR2C-related disorder	Likely benign (Feb 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HTR2C	protein_coding	protein_coding	ENST00000276198	4	326074

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0370	0.932	125714	2	3	125719	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.21	147	194	0.756	0.0000159	3008
Missense in Polyphen		21	55.351	0.3794		901
Synonymous	0.960	70	81.0	0.864	0.00000736	935
Loss of Function	1.87	4	10.6	0.379	8.59e-7	168

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000771	0.0000771
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000261	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000566	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1- 2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis. {ECO:0000269|PubMed:12970106, ECO:0000269|PubMed:18703043, ECO:0000269|PubMed:19057895, ECO:0000269|PubMed:7895773}.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Gap junction - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics;Serotonin and anxiety;Serotonin and anxiety-related events;Prader-Willi and Angelman Syndrome;GPCRs, Class A Rhodopsin-like;Monoamine GPCRs;Serotonin Receptor 2 and ELK-SRF-GATA4 signaling;Signaling by GPCR;Signal Transduction;ion channels and their functional role in vascular endothelium;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;chrebp regulation by carbohydrates and camp;role of -arrestins in the activation and targeting of map kinases;activation of camp-dependent protein kinase pka;Ghrelin;Serotonin receptors;Amine ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);roles of arrestin dependent recruitment of src kinases in gpcr signaling;GPCR ligand binding;-arrestins in gpcr desensitization;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.224

Intolerance Scores

• loftool: 0.704
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.32

Haploinsufficiency Scores

• pHI: 0.361
• hipred: Y
• hipred_score: 0.554
• ghis: 0.500

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.710

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Htr2c
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: behavioral fear response;cellular calcium ion homeostasis;G protein-coupled receptor signaling pathway;G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger;phospholipase C-activating G protein-coupled receptor signaling pathway;phospholipase C-activating serotonin receptor signaling pathway;serotonin receptor signaling pathway;chemical synaptic transmission;locomotory behavior;feeding behavior;positive regulation of phosphatidylinositol biosynthetic process;cGMP-mediated signaling;regulation of neurological system process;regulation of appetite;response to drug;regulation of corticotropin-releasing hormone secretion;positive regulation of fat cell differentiation;release of sequestered calcium ion into cytosol;positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway;positive regulation of ERK1 and ERK2 cascade
• Cellular component: plasma membrane;integral component of plasma membrane;dendrite
• Molecular function: Gq/11-coupled serotonin receptor activity;G protein-coupled receptor activity;G protein-coupled serotonin receptor activity;drug binding;neurotransmitter receptor activity;serotonin binding;1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding