HTR1A

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

Basic information

Region (hg38): 5:63957873-63962507

Previous symbols: [ "ADRB2RL1", "ADRBRL1" ]

Links

ENSG00000178394 ∙ NCBI:3350 ∙ OMIM:109760 ∙ HGNC:5286 ∙ Uniprot:P08908 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• menstrual cycle-dependent periodic fever (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Periodic fever, menstrual cycle dependent	AD	Allergy/Immunology/Infectious	Fevers have been reported as responding to medical treatments such as HTR1A-agonists	Allergy/Immunology/Infectious; Endocrine; Obstetric	21990073
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

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HTR1A gene.

• not provided (15 variants)
• Inborn genetic diseases (8 variants)
• not specified (2 variants)
• Menstrual cycle-dependent periodic fever (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HTR1A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	1	7
missense			8	5	3	16
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	9	11	4

Variants in HTR1A

This is a list of pathogenic ClinVar variants found in the HTR1A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-63960680-AGCGTCTTCACTGTCTTCCTCTCTCGGGCCAGGGCCATCTTGCGCTTCGCCTCGGCGTTGC-A		Menstrual cycle-dependent periodic fever	Uncertain significance (Dec 02, 2022)
5-63960704-C-CG			Uncertain significance (Jan 01, 2024)
5-63960718-C-T			Likely benign (Sep 01, 2022)
5-63960720-T-G			Likely benign (Jul 01, 2022)
5-63960745-A-G		HTR1A-related disorder	Likely benign (Jan 20, 2020)
5-63960765-C-T		not specified	Uncertain significance (Jan 27, 2022)
5-63960818-G-A		not specified	Uncertain significance (Jun 02, 2023)
5-63960831-G-C		not specified	Uncertain significance (Dec 22, 2023)
5-63960859-G-A			Likely benign (Dec 31, 2019)
5-63960862-A-G			Likely benign (May 01, 2023)
5-63960865-G-C		not specified	Likely benign (Oct 02, 2023)
5-63960902-C-T			Benign (Dec 31, 2019)
5-63960941-C-T		not specified	Uncertain significance (Feb 26, 2024)
5-63960967-C-G		not specified	Uncertain significance (Aug 04, 2023)
5-63960972-G-A		not specified	Uncertain significance (Jul 16, 2021)
5-63960983-G-T		not specified	Uncertain significance (Jan 23, 2024)
5-63961011-C-T			Likely benign (Aug 01, 2023)
5-63961046-C-T		not specified	Uncertain significance (Jul 15, 2021)
5-63961061-C-A			Benign/Likely benign (Apr 01, 2024)
5-63961175-G-A			Benign/Likely benign (Jul 01, 2022)
5-63961255-C-A			Likely benign (May 23, 2018)
5-63961256-G-C		HTR1A-related disorder	Likely benign (Feb 01, 2024)
5-63961297-G-A			Benign (Dec 31, 2019)
5-63961304-G-A		not specified	Uncertain significance (Sep 22, 2022)
5-63961330-G-T		not specified	Likely benign (Mar 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HTR1A	protein_coding	protein_coding	ENST00000323865	1	2152

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.200	0.791	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.637	227	256	0.888	0.0000159	2718
Missense in Polyphen		85	127.87	0.66471		1388
Synonymous	-0.112	119	117	1.01	0.00000838	920
Loss of Function	2.25	3	11.1	0.270	6.54e-7	110

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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}.
• Pathway: 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;Levomethadyl Acetate Action Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Escitalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Levallorphan Action Pathway;Dimethylthiambutene Action Pathway;Ethylmorphine Action Pathway;Pentazocine Action Pathway;Naltrexone Action Pathway;Buprenorphine Action Pathway;Alvimopan Action Pathway;Naloxone Action Pathway;Dihydromorphine Action Pathway;Nicotine Action Pathway;Nalbuphine Action Pathway;Ketobemidone Action Pathway;Lidocaine (Local Anaesthetic) Action Pathway;Mepivacaine Action Pathway;Chloroprocaine Action Pathway;Cocaine Action Pathway;Dibucaine Action Pathway;Levobupivacaine Action Pathway;Benzocaine Action Pathway;Bupivacaine Action Pathway;Levorphanol Action Pathway;Propoxyphene Action Pathway;Tramadol Action Action Pathway;Diphenoxylate Action Pathway;Anileridine Action Pathway;Methadone Action Pathway;Oxycodone Action Pathway;Oxybuprocaine Action Pathway;Prilocaine Action Pathway;Procaine Action Pathway;Proparacaine Action Pathway;Ropivacaine Action Pathway;Codeine Action Pathway;Morphine Action Pathway;Heroin Action Pathway;Alfentanil Action Pathway;Oxymorphone Action Pathway;Hydrocodone Action Pathway;Hydromorphone Action Pathway;Sufentanil Action Pathway;Remifentanil Action Pathway;Fentanyl Action Pathway;Carfentanil Action Pathway;3-Methylthiofentanyl Action Pathway;Methadyl Acetate Action Pathway;Dezocine Action Pathway;Serotonin and anxiety;Serotonin and anxiety-related events;GPCRs, Class A Rhodopsin-like;Monoamine GPCRs;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Serotonin HTR1 Group and FOS Pathway;Signaling by GPCR;Signal Transduction;Serotonin receptors;Amine ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.204

Intolerance Scores

• rvis_EVS: -0.2
• rvis_percentile_EVS: 38.82

Haploinsufficiency Scores

• pHI: 0.497
• hipred: Y
• hipred_score: 0.851
• ghis: 0.450

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.904

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Htr1a
• Phenotype: homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: htr1ab
• Affected structure: spinal cord
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• 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;chemical synaptic transmission;cell population proliferation;positive regulation of cell population proliferation;regulation of serotonin secretion;exploration behavior;regulation of dopamine metabolic process;vasoconstriction;serotonin metabolic process;regulation of hormone secretion;regulation of behavior
• Cellular component: plasma membrane;integral component of plasma membrane;dendrite
• Molecular function: G protein-coupled receptor activity;G protein-coupled serotonin receptor activity;protein binding;neurotransmitter receptor activity;serotonin binding;receptor-receptor interaction