HTR6
protein-coding5-hydroxytryptamine receptor 6, the group of 5-hydroxytryptamine receptors, G protein-coupled
Gene summary
This gene encodes a protein that belongs to the seven-transmembrane G protein-coupled receptor family of proteins. The encoded protein couples with the Gs alpha subunit and stimulates adenylate cyclase to activate the cyclic AMP-dependent signaling pathway. This receptor is thought to regulate cholinergic neuronal transmission in the brain. Several antidepressants and antipsychotic drugs have a high affinity for this receptor. [provided by RefSeq, Aug 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.1 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 HTR6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000871.3. 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 | 5 | 7 | |||
| missense | 72 | 6 | 1 | 79 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 72 | 8 | 6 | 86 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000862.1 | 3 | MANE Select | |
| Ensembl | ENSP00000289753.1 | 3 | MANE Select | |
| Ensembl | ENSP00000804743.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Serotonergic synapse - Homo sapiens (human)
- Calcium signaling pathway - Homo sapiens (human)
- cAMP signaling pathway - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics
Biological Process
- G protein-coupled receptor signaling pathway
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- chemical synaptic transmission
- cerebral cortex cell migration
- positive regulation of TOR signaling
Molecular Function
- G protein-coupled receptor activity
- histamine receptor activity
- G protein-coupled serotonin receptor activity
- protein binding
- neurotransmitter receptor activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- cilium
- dendrite
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000289753
- Coding exons
- 3
- Length
- 14276
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125746
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.343 | 276 | 293 | 0.944 | 0.0000186 | 2738 |
| Missense (PolyPhen) | 85 | 95.636 | 0.88879 | 1006 | ||
| Synonymous | -0.915 | 154 | 140 | 1.10 | 0.00000892 | 1037 |
| Loss of Function | 0.953 | 7 | 10.3 | 0.680 | 4.42e-7 | 104 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
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. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611). {ECO:0000250|UniProtKB:P31388, ECO:0000250|UniProtKB:Q9R1C8, ECO:0000269|PubMed:23027611}.;
Recessive Scores
- pRec
- 0.151
Intolerance Scores
- LoFtool
- 0.571
- RVIS EVS
- -0.65
- RVIS percentile EVS
- 16.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.334
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |