HTR1D
protein-coding5-hydroxytryptamine receptor 1D, the group of 5-hydroxytryptamine receptors, G protein-coupled
Gene summary
Enables Gi/o-coupled serotonin receptor activity. Involved in adenylate cyclase-inhibiting serotonin receptor signaling pathway and intestine smooth muscle contraction. Located in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]
- HTRL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.6 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 HTR1D variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000864.5. 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 | 64 | 1 | 1 | 66 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 64 | 1 | 3 | 68 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000855.1 | 1 | MANE Select | |
| Ensembl | ENSP00000363748.1 | 1 | MANE Select | |
| Ensembl | ENSP00000588634.1 | 1 | Standard | |
| Ensembl | ENSP00000588634.1 | 1 | Standard |
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 signaling pathway
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- chemical synaptic transmission
- intestine smooth muscle contraction
Molecular Function
- G protein-coupled receptor activity
- G protein-coupled serotonin receptor activity
- neurotransmitter receptor activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- dendrite
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374619
- Coding exons
- 1
- Length
- 4230
- 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 | 0.0899 | 221 | 225 | 0.983 | 0.0000134 | 2427 |
| Missense (PolyPhen) | 91 | 98.051 | 0.92809 | 1096 | ||
| Synonymous | 0.271 | 97 | 100 | 0.966 | 0.00000630 | 839 |
| Loss of Function | 0.957 | 6 | 9.12 | 0.658 | 4.57e-7 | 100 |
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. 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. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction. {ECO:0000269|PubMed:10452531, ECO:0000269|PubMed:1565658, ECO:0000269|PubMed:1652050}.;
Recessive Scores
- pRec
- 0.210
Intolerance Scores
- LoFtool
- 0.216
- RVIS EVS
- -0.54
- RVIS percentile EVS
- 20.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.804
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |