HTR3A
protein-coding5-hydroxytryptamine receptor 3A, the group of 5-hydroxytryptamine receptors, ionotropic
Gene summary
The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit A of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor causes fast, depolarizing responses in neurons after activation. It appears that the heteromeric combination of A and B subunits is necessary to provide the full functional features of this receptor, since either subunit alone results in receptors with very low conductance and response amplitude. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
- HTR3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.2 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 HTR3A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000869.6. 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 | 4 | 3 | 3 | 10 | ||
| missense | 83 | 2 | 1 | 86 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 90 | 5 | 4 | 99 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000860.3 | 9 | MANE Select | |
| Ensembl | ENSP00000424189.2 | 9 | MANE Select | |
| RefSeq | NP_001155244.1 | 9 | Standard | |
| RefSeq | NP_998786.3 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Serotonergic synapse - Homo sapiens (human)
- Taste transduction - Homo sapiens (human)
- Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics
- Selective serotonin reuptake inhibitors lead to several adverse outcomes
- Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
Biological Process
- signal transduction
- serotonin receptor signaling pathway
- chemical synaptic transmission
- positive regulation of ion transmembrane transporter activity
- ion transmembrane transport
Molecular Function
- transmembrane signaling receptor activity
- extracellular ligand-gated ion channel activity
- protein binding
- serotonin-gated cation-selective channel activity
- serotonin binding
Cellular Component
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- cell junction
- axon
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000355556
- Coding exons
- 8
- Length
- 15433
- Individuals with no LoFs
- 125497
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 249
- Defined
- 125748
- p
- 0.000999
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.17 | 350 | 294 | 1.19 | 0.0000187 | 3334 |
| Missense (PolyPhen) | 120 | 113.43 | 1.0579 | 1335 | ||
| Synonymous | -0.533 | 136 | 128 | 1.06 | 0.00000860 | 1075 |
| Loss of Function | 1.03 | 18 | 23.4 | 0.769 | 0.00000129 | 244 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.012 | 0.012 | notable |
| Latino/Admixed American | 0.00061 | 0.00061 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00092 | 0.00092 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel. {ECO:0000269|PubMed:12867984, ECO:0000269|PubMed:9950429}.;
Recessive Scores
- pRec
- 0.241
Intolerance Scores
- LoFtool
- 0.202
- RVIS EVS
- -1.11
- RVIS percentile EVS
- 6.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.264
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |