HTR1B
protein-coding5-hydroxytryptamine receptor 1B, the group of 5-hydroxytryptamine receptors, G protein-coupled
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HTR1B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000863.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 32 | 3 | 35 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 32 | 5 | 0 | 37 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000854.1 | 1 | MANE Select | |
| Ensembl | ENSP00000358963.3 | 1 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Serotonergic synapse - Homo sapiens (human)
- cAMP signaling pathway - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Taste transduction - Homo sapiens (human)
- Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics
Biological Process
- G protein-coupled receptor internalization
- G protein-coupled receptor signaling pathway
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- adenylate cyclase-inhibiting serotonin receptor signaling pathway
Molecular Function
- G protein-coupled receptor activity
- G protein-coupled serotonin receptor activity
- protein binding
- drug binding
- neurotransmitter receptor activity
Cellular Component
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- dendrite
- calyx of Held
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369947
- Coding exons
- 1
- Length
- 1543
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.778 | 181 | 213 | 0.850 | 0.0000101 | 2498 |
| Missense (PolyPhen) | 35 | 74.812 | 0.46784 | 901 | ||
| Synonymous | -1.32 | 109 | 92.8 | 1.17 | 0.00000456 | 862 |
| Loss of Function | 2.22 | 3 | 10.9 | 0.275 | 4.81e-7 | 116 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries. {ECO:0000269|PubMed:10452531, ECO:0000269|PubMed:1315531, ECO:0000269|PubMed:1328844, ECO:0000269|PubMed:1348246, ECO:0000269|PubMed:1351684, ECO:0000269|PubMed:1559993, ECO:0000269|PubMed:1565658, ECO:0000269|PubMed:15853772, ECO:0000269|PubMed:1610347, ECO:0000269|PubMed:23519210, ECO:0000269|PubMed:23519215, ECO:0000269|PubMed:8218242}.;
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- LoFtool
- 0.0732
- RVIS EVS
- -0.4
- RVIS percentile EVS
- 26.53
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.837
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |