HTR1B

Chr 6

5-hydroxytryptamine receptor 1B

Also known as: 5-HT-1B, 5-HT-1D-beta, 5-HT1B, 5-HT1DB, HTR1D2, HTR1DB, S12

NCBI Gene: 3351ENSG00000135312UniProt: P28222

The protein encoded by this intronless gene is a G-protein coupled receptor for serotonin (5-hydroxytryptamine). Ligand binding activates second messengers that inhibit the activity of adenylate cyclase and manage the release of serotonin, dopamine, and acetylcholine in the brain. The encoded protein may be involved in several neuropsychiatric disorders and therefore is often a target of antidepressant and other psychotherapeutic drugs. [provided by RefSeq, Nov 2015]

55
ClinVar variants
13
Pathogenic / LP
0.19
pLI score
0
Active trials
Clinical Summary— HTR1B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 37 VUS of 55 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.71LOEUF
pLI 0.189
Z-score 2.22
OE 0.27 (0.12–0.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.78Z-score
OE missense 0.85 (0.75–0.96)
181 obs / 213.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.27 (0.12–0.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.75–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 3 / 10.9Missense obs/exp: 181 / 213.0Syn Z: -1.32

ClinVar Variant Classifications

55 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
VUS37
Likely Benign5
13
Pathogenic
37
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
0
0
0
VUS
0
32
5
0
37
Likely Benign
0
3
0
2
5
Benign
0
0
0
0
0
Total03518255

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HTR1B · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Molecular genetics of attention-deficit/hyperactivity disorder.
Faraone SV et al.·Biol Psychiatry
2005Review
HTR1B genotype and psychopathy: Main effect and interaction with paternal maltreatment.
Palumbo S et al.·Psychoneuroendocrinology
2022
DNA variation and psychopharmacology of the human serotonin receptor 1B (HTR1B) gene.
Sanders AR et al.·Pharmacogenomics
2002Review
Association of OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 polymorphisms with clinical phenotype among women with fibromyalgia.
Fernández-de-Las-Peñas C et al.·Sci Rep
2024
Epigenetic and genetic variants in the HTR1B gene and clinical improvement in children and adolescents treated with fluoxetine.
Gassó P et al.·Prog Neuropsychopharmacol Biol Psychiatry
2017
Effects of serotonin transporter and receptor polymorphisms on depression.
López-Echeverri YP et al.·Rev Colomb Psiquiatr (Engl Ed)
2023Review
Molecular mechanisms of quetiapine bidirectional regulation of bipolar depression and mania based on network pharmacology and molecular docking: Evidence from computational biology.
Li C et al.·J Affect Disord
2024Functional
Lrp5 and bone formation : A serotonin-dependent pathway.
Yadav VK et al.·Ann N Y Acad Sci
2010Review
Single-Nucleotide Polymorphisms as Biomarkers of Antipsychotic-Induced Akathisia: Systematic Review.
Nasyrova RF et al.·Genes (Basel)
2023Review
ADHD genetics: 2007 update.
Elia J et al.·Curr Psychiatry Rep
2007Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools