HTR2A

5-hydroxytryptamine receptor 2A, the group of 5-hydroxytryptamine receptors, G protein-coupled

Basic information

Region (hg38): 13:46831545-46897076

Previous symbols: [ "HTR2" ]

Links

ENSG00000102468 ∙ NCBI:3356 ∙ OMIM:182135 ∙ HGNC:5293 ∙ Uniprot:P28223 ∙ 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
Major depressive disorder, response to citalopram therapy in; Clozapine, response to	AD	Pharmacogenomic	Variants may relate to the efficacy of medications such as Citalopram and clozapine	General	9491814; 12563180; 16642436

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HTR2A gene.

• not provided (10 variants)
• Inborn genetic diseases (5 variants)
• not specified (3 variants)
• Major depressive disorder, response to citalopram therapy in (1 variants)
• Schizophrenia, susceptibility to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HTR2A 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				6	2	8
missense			5	1		6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding				1	2	3
Total	0	0	6	8	4

Variants in HTR2A

This is a list of pathogenic ClinVar variants found in the HTR2A region.

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

Position	Type	Phenotype	Significance	ClinVar
13-46834913-G-A		HTR2A-related disorder	Likely benign (May 12, 2020)
13-46834914-C-T		not specified	Uncertain significance (Jan 26, 2022)
13-46834993-C-T			Likely benign (Aug 06, 2018)
13-46835155-A-G			Likely benign (Dec 20, 2017)
13-46835316-G-T		not specified	Uncertain significance (Oct 03, 2023)
13-46835319-T-C		not specified	Uncertain significance (Oct 13, 2023)
13-46835509-G-A			Likely benign (Aug 22, 2018)
13-46835566-G-A			Benign (May 21, 2018)
13-46835596-C-T			Likely benign (Jul 21, 2018)
13-46837850-A-G		Major depressive disorder, response to citalopram therapy in • not specified	Benign (Mar 09, 2018)
13-46892449-C-T		not specified	Uncertain significance (Jan 04, 2022)
13-46892532-G-C			Likely benign (Nov 01, 2022)
13-46892584-C-T		not specified	Uncertain significance (Jul 06, 2021)
13-46892589-C-T		not specified	Likely benign (Feb 28, 2024)
13-46895494-C-G			Uncertain significance (Mar 26, 2021)
13-46895679-C-A		not specified	Uncertain significance (Jan 16, 2024)
13-46895721-T-G			Likely benign (May 21, 2018)
13-46895780-A-C		not specified	Uncertain significance (May 04, 2023)
13-46895805-G-A		not specified	Likely benign (Mar 09, 2018)
13-46895805-G-G		not specified • Schizophrenia, susceptibility to	Benign (Feb 27, 2018)
13-46895821-C-G		not specified	Uncertain significance (Dec 21, 2023)
13-46895856-G-A			Benign (Dec 11, 2017)
13-46895900-T-A		not specified	Uncertain significance (Jan 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HTR2A	protein_coding	protein_coding	ENST00000378688	3	65485

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.511	0.488	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.75	177	256	0.692	0.0000145	3083
Missense in Polyphen		54	115.73	0.46661		1386
Synonymous	-0.147	109	107	1.02	0.00000670	935
Loss of Function	2.86	3	14.9	0.201	7.07e-7	189

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000984	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4- iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:28129538). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors (PubMed:28129538). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538). Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores (PubMed:18703043, PubMed:28129538). Affects neural activity, perception, cognition and mood (PubMed:18297054). Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction. {ECO:0000269|PubMed:1330647, ECO:0000269|PubMed:18297054, ECO:0000269|PubMed:18703043, ECO:0000269|PubMed:19057895, ECO:0000269|PubMed:21645528, ECO:0000269|PubMed:22300836, ECO:0000269|PubMed:28129538}.
• 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;GPCRs, Other;Serotonin and anxiety;Serotonin and anxiety-related events;Selective serotonin reuptake inhibitors lead to several adverse outcomes;GPCRs, Class A Rhodopsin-like;Monoamine GPCRs;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Serotonin Receptor 2 and ELK-SRF-GATA4 signaling;Serotonin Receptor 2 and STAT3 Signaling;Signaling by GPCR;Signal Transduction;Serotonin receptors;Amine ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.342

Intolerance Scores

• loftool: 0.186
• rvis_EVS: 0.44
• rvis_percentile_EVS: 77.8

Haploinsufficiency Scores

• pHI: 0.414
• hipred: Y
• hipred_score: 0.783
• ghis: 0.413

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.621

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Htr2a
• Phenotype: muscle phenotype; endocrine/exocrine gland phenotype; digestive/alimentary phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: htr2ab
• Affected structure: commissure of the tract of the commissure of the caudal tuberculum
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: temperature homeostasis;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;activation of phospholipase C activity;phospholipase C-activating serotonin receptor signaling pathway;serotonin receptor signaling pathway;chemical synaptic transmission;aging;memory;cell death;positive regulation of cell population proliferation;positive regulation of phosphatidylinositol biosynthetic process;regulation of dopamine secretion;phosphatidylinositol 3-kinase signaling;artery smooth muscle contraction;urinary bladder smooth muscle contraction;sleep;response to drug;negative regulation of potassium ion transport;positive regulation of MAP kinase activity;protein localization to cytoskeleton;positive regulation of fat cell differentiation;positive regulation of glycolytic process;positive regulation of vasoconstriction;viral entry into host cell;behavioral response to cocaine;positive regulation of peptidyl-tyrosine phosphorylation;detection of temperature stimulus involved in sensory perception of pain;detection of mechanical stimulus involved in sensory perception of pain;release of sequestered calcium ion into cytosol;negative regulation of synaptic transmission, glutamatergic;positive regulation of ERK1 and ERK2 cascade;regulation of synaptic vesicle exocytosis
• Cellular component: cytosol;plasma membrane;integral component of plasma membrane;caveola;axon;dendrite;cytoplasmic vesicle;neuronal cell body;dendritic shaft;cell body fiber;glutamatergic synapse;integral component of postsynaptic membrane;integral component of presynaptic membrane
• Molecular function: virus receptor activity;G-protein alpha-subunit binding;G protein-coupled receptor activity;G protein-coupled serotonin receptor activity;drug binding;neurotransmitter receptor activity;protein-containing complex binding;serotonin binding;1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding