HTR2C

Chr X

5-hydroxytryptamine receptor 2C

Also known as: 5-HT1C, 5-HT2C, 5-HTR2C, 5HTR2C, HTR1C

The HTR2C protein is a G-protein-coupled receptor that responds to serotonin signaling and activates phospholipase C-beta through G(q)/G(11) proteins, modulating neuronal activity, appetite regulation, and stress responses. Mutations in HTR2C cause X-linked intellectual disability with associated features that may include obesity, behavioral problems, and seizures. This gene follows X-linked inheritance and has low constraint against loss-of-function variants.

Summary from RefSeq, UniProt
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0
Active trials
24
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.87
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryHTR2C
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.037
Z-score 1.87
OE 0.38 (0.190.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.21Z-score
OE missense 0.76 (0.660.87)
147 obs / 194.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.190.87)
00.351.4
Missense OE0.76 (0.660.87)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 4 / 10.6Missense obs/exp: 147 / 194.3Syn Z: 0.96
DN
0.76top 25%
GOF
0.83top 10%
LOF
0.2873th %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

HTR2C · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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