Human Gene Module / Chromosome 11 / HTR3A

HTR3A5-hydroxytryptamine (serotonin) receptor 3A

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 9
Rare Variants / Common Variants
8 / 1
Aliases
-
Associated Syndromes
-
Chromosome Band
11q23.2
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the HTR3A gene and autism in a Caucasian-American population cohort (Anderson et al., 2009). In addition, genetic association has been found between HTR3A and therapeutic response to risperidone treatment in Chinese schizophrenic patients.

Molecular Function

ligand-gated ion channel receptor

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
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Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to HTR3A (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited A cytoplasmic region determines single-channel conductance in 5-HT3 receptors Kelley SP , et al. (2003) No -
2 Highly Cited Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel Maricq AV , et al. (1991) No -
3 Recent Recommendation Association between a polymorphism of the HTR3A gene and therapeutic response to risperidone treatment in drug-naive Chinese schizophrenia patients Gu B , et al. (2008) No -
4 Recent Recommendation Neurogenesis and widespread forebrain migration of distinct GABAergic neurons from the postnatal subventricular zone Inta D , et al. (2008) No -
5 Primary Examination of association of genes in the serotonin system to autism Anderson BM , et al. (2009) Yes -
6 Recent Recommendation Expression analysis of green fluorescent protein in retinal neurons of four transgenic mouse lines Haverkamp S , et al. (2009) No -
7 Support Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy Klassen T , et al. (2011) No -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - intron_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.219G>A p.Val73%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.419G>A p.Arg140Gln missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.161G>T p.Gly54Val missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.353C>T p.Thr118Met missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.1044G>T p.Trp348Cys missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.705dup p.Val236CysfsTer58 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.559del p.Ile187SerfsTer10 frameshift_variant Familial Maternal Multiplex (monozygotic twins) 37506195 Cirnigliaro M et al. (2023)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.1156+118G>A;c.1093+118G>A;c.1252+118G>A - intron_variant - - - 19184136 Anderson BM , et al. (2009)
SFARI Gene score
2

Strong Candidate

Initial candidate gene study with > 400 families provides nominal significance for involvement (uncorrected p = 0.0002), separate study suggests that separate allele may show nominally significant association (Rehnstr?m K, et al)

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Initial candidate gene study with > 400 families provides nominal significance for involvement (uncorrected p = 0.0002), separate study suggests that separate allele may show nominally significant association (Rehnstr?m K, et al)

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Initial candidate gene study with > 400 families provides nominal significance for involvement (uncorrected p = 0.0002), separate study suggests that separate allele may show nominally significant association (Rehnstr?m K, et al)

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Initial candidate gene study with > 400 families provides nominal significance for involvement (uncorrected p = 0.0002), separate study suggests that separate allele may show nominally significant association (Rehnstr?m K, et al)

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Initial candidate gene study with > 400 families provides nominal significance for involvement (uncorrected p = 0.0002), separate study suggests that separate allele may show nominally significant association (Rehnstr?m K, et al)

Krishnan Probability Score

Score 0.49847854968603

Ranking 2240/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 1.0283942233574E-9

Ranking 16597/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.65390508291363

Ranking 913/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Larsen Cumulative Evidence Score

Score 1

Ranking 424/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score -0.23071399585093

Ranking 16027/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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