HTR2A
Chr 13AD5-hydroxytryptamine receptor 2A
Also known as: 5-HT2A, HTR2
This gene encodes a G-protein coupled receptor for serotonin that activates phospholipase C-beta signaling and affects neural activity, perception, cognition and mood. Mutations are associated with susceptibility to schizophrenia and obsessive-compulsive disorder, as well as altered response to antidepressant therapy in major depressive disorder. The inheritance pattern is autosomal dominant.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
106 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 55 | 0 | 55 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 1 | 27 | 3 | 0 | 31 |
Likely Benign | 0 | 1 | 1 | 8 | 10 |
Benign | 0 | 0 | 2 | 2 | 4 |
| Total | 1 | 28 | 62 | 10 | 101 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HTR2A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
mRNA Expression and Genetic Polymorphisms Affecting DRD3 (rs6280) and HTR2A (rs6313) in Bruxism
NOT YET RECRUITINGPain, Central Sensitization and Psychoemotional State in Patients With Chronic Masticatory Muscle Pain
ENROLLING BY INVITATIONEfficacy of a Prediction Model-based Algorithm to PREVENT Drug-induced Impulse Control Disorders in Parkinson's Disease
NOT YET RECRUITINGThe Effects of Psilocybin in Healthy Volunteers: Psychological, Biochemical and Electrophysiological Biomarkers.
NOT YET RECRUITINGA Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools