HTR2B
Chr 25-hydroxytryptamine receptor 2B
Also known as: 5-HT(2B), 5-HT-2B, 5-HT2B
The protein encoded by this gene is a G-protein coupled receptor for serotonin that regulates neurotransmitter release, cardiovascular function, heart development, and bone density through activation of phospholipase C signaling pathways. Mutations cause autosomal recessive disorders affecting multiple systems including the heart, bones, and nervous system, with manifestations that can include cardiac abnormalities and behavioral changes. This gene is extremely intolerant to loss-of-function mutations (very low pLI and high LOEUF scores), indicating that complete loss of protein function is likely to cause significant disease.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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
103 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 | 28 | 0 | 28 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 61 | 3 | 0 | 64 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 4 | 0 | 2 | 6 |
| Total | 0 | 67 | 31 | 2 | 100 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HTR2B · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools