GeneBe

HTR1A

protein-coding

5-hydroxytryptamine receptor 1A, the group of 5-hydroxytryptamine receptors, G protein-coupled

Gene summary

This gene encodes a G protein-coupled receptor for 5-hydroxytryptamine (serotonin), and belongs to the 5-hydroxytryptamine receptor subfamily. Serotonin has been implicated in a number of physiologic processes and pathologic conditions. Inactivation of this gene in mice results in behavior consistent with an increased anxiety and stress response. Mutation in the promoter of this gene has been associated with menstrual cycle-dependent periodic fevers. [provided by RefSeq, Jun 2012]

Previous symbols:
  • ADRB2RL1
  • ADRBRL1

MANE transcript

NM_000524.4

Inheritance

AD

ClinVar variants

U:41B:18

Top phenotype

Periodic fever, menstrual cycle dependent

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr5:63,957,874-63,962,507

External References & Databases

Ensembl (ENSG00000178394)NCBI Gene (3350)OMIM (109760)HGNC:5286GenCCUniProt (P08908)AlphaFoldClinVar (HTR1A)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~4.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

menstrual cycle-dependent periodic feverLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0044660

Submitter: PanelApp Australia

menstrual cycle-dependent periodic feverLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0044660

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Periodic fever, menstrual cycle dependentAD

Manifestation: Allergy/Immunology/Infectious; Endocrine; Obstetric

Intervention: Allergy/Immunology/Infectious

Rationale: Fevers have been reported as responding to medical treatments such as HTR1A-agonists

Comments: As the disorder affects females, the onset may be in the pediatric timeframe due to the typical age of menarche, though reported individuals have been typically described as older

Refs: 21990073Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HTR1A variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 45
not providedTotal: 16
HTR1A-related disorderTotal: 6
Menstrual cycle-dependent periodic feverTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000524.4. 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.

EffectPLPVUSLBBSum
synonymous
8
clinvar
 8
missense
40
clinvar
7
clinvar
3
clinvar
 50
nonsense
0
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
0
Total004115359
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000524.4RefSeqNP_000515.21MANE Select
ENST00000323865.5EnsemblENSP00000316244.41MANE Select
ENST00000506598.1EnsemblENSP00000423433.11Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
htr1abDanio rerio

Structure: spinal cord

Quality: decreased amount

abnormal

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

  • behavioral fear response
  • G protein-coupled receptor signaling pathway
  • G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
  • adenylate cyclase-inhibiting serotonin receptor signaling pathway
  • serotonin receptor signaling pathway

Molecular Function

  • G protein-coupled receptor activity
  • G protein-coupled serotonin receptor activity
  • protein binding
  • neurotransmitter receptor activity
  • serotonin binding

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • dendrite

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000323865
Coding exons
1
Length
2152
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.6372272560.8880.00001592718
Missense (PolyPhen)85127.870.664711388
Synonymous-0.1121191171.010.00000838920
Loss of Function2.25311.10.2706.54e-7110

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and 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. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5- hydroxytryptamine release and in the regulation of dopamine and 5- hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli. {ECO:0000269|PubMed:22957663, ECO:0000269|PubMed:3138543, ECO:0000269|PubMed:8138923, ECO:0000269|PubMed:8393041}.;

Recessive Scores

pRec
0.204

Intolerance Scores

RVIS EVS
-0.2
RVIS percentile EVS
38.82

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.904

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.