HTR2A

Chr 13AD

5-hydroxytryptamine receptor 2A

Also known as: 5-HT2A, HTR2

This gene encodes one of the receptors for serotonin, a neurotransmitter with many roles. Mutations in this gene are associated with susceptibility to schizophrenia and obsessive-compulsive disorder, and are also associated with response to the antidepressant citalopram in patients with major depressive disorder (MDD). MDD patients who also have a mutation in intron 2 of this gene show a significantly reduced response to citalopram as this antidepressant downregulates expression of this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

{Major depressive disorder, response to citalopram therapy in}MIM #608516
{Obsessive-compulsive disorder, susceptibility to}MIM #164230
AD
{Schizophrenia, susceptibility to}MIM #181500
AD
4
Active trials
92
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.52
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryHTR2A
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.51) — some intolerance to loss-of-function variants.
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.511
Z-score 2.86
OE 0.20 (0.090.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.75Z-score
OE missense 0.69 (0.610.78)
177 obs / 255.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.090.52)
00.351.4
Missense OE0.69 (0.610.78)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 3 / 14.9Missense obs/exp: 177 / 255.7Syn Z: -0.15
DN
0.7036th %ile
GOF
0.78top 25%
LOF
0.3941th %ile

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.

GOFprediction above median
DNprediction above median

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

0 submitted variants 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.

Clinical Literature
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