HTR3C5-hydroxytryptamine (serotonin) receptor 3, family member C
Autism Reports / Total Reports
4 / 8Rare Variants / Common Variants
7 / 3Aliases
-Associated Syndromes
-Chromosome Band
3q27.1Associated Disorders
-Relevance to Autism
Genetic association has been found between the HTR3C gene and autism in a Finnish population cohort (Rehnstrm et al., 2009).
Molecular Function
Ligand-gated ion channel receptor
External Links
SFARI Genomic Platforms
Reports related to HTR3C (8 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Cloning, physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C, HTR3D and HTR3E | Niesler B , et al. (2003) | No | - |
| 2 | Recent Recommendation | Serotonin type 3 receptor genes: HTR3A, B, C, D, E | Niesler B , et al. (2008) | No | - |
| 3 | Recent Recommendation | The 5-HT3 receptor--the relationship between structure and function | Barnes NM , et al. (2008) | No | - |
| 4 | Primary | Allelic variants in HTR3C show association with autism | Rehnstrm K , et al. (2008) | Yes | - |
| 5 | Support | Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy | Klassen T , et al. (2011) | No | - |
| 6 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
| 7 | Support | - | Zhou X et al. (2022) | Yes | - |
| 8 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
Rare Variants (7)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.885G>A | p.Met295Ile | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.78C>T | p.Asp26= | synonymous_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
| c.870C>T | p.Asn290= | synonymous_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
| c.1154C>T | p.Pro385Leu | missense_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
| c.1279T>C | p.Phe427Leu | missense_variant | Unknown | - | Unknown | 21703448 | Klassen T , et al. (2011) | |
| c.284G>A | p.Trp95Ter | stop_gained | Familial | Paternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| c.532_536del | p.Phe178LeufsTer56 | frameshift_variant | Familial | Maternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) |
Common Variants (3)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | N/A | downstream_gene_variant | - | - | - | 19035560 | Rehnstrm K , et al. (2008) | |
| c.489C>A | p.Asn163Lys | missense_variant | - | - | - | 19035560 | Rehnstrm K , et al. (2008) | |
| c.1214G>C | p.Gly405Ala | missense_variant | - | - | - | 19035560 | Rehnstrm K , et al. (2008) |
SFARI Gene score
2
Strong Candidate
In region of linkage in Finnish families. Subsequent association in region with 2 non-synonymous SNPs, but not multi-test significant (PMID: 19035560).
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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
2
Decreased from 3 to 2
Description
In region of linkage in Finnish families. Subsequent association in region with 2 non-synonymous SNPs, but not multi-test significant (PMID: 19035560).
10/1/2019
4
3
Decreased from 4 to 3
New Scoring Scheme
Description
In region of linkage in Finnish families. Subsequent association in region with 2 non-synonymous SNPs, but not multi-test significant (PMID: 19035560).
Reports Added
[New Scoring Scheme]7/1/2019
4
4
Decreased from 4 to 4
Description
In region of linkage in Finnish families. Subsequent association in region with 2 non-synonymous SNPs, but not multi-test significant (PMID: 19035560).
7/1/2014
No data
4
Increased from No data to 4
Description
In region of linkage in Finnish families. Subsequent association in region with 2 non-synonymous SNPs, but not multi-test significant (PMID: 19035560).
4/1/2014
No data
4
Increased from No data to 4
Description
In region of linkage in Finnish families. Subsequent association in region with 2 non-synonymous SNPs, but not multi-test significant (PMID: 19035560).
Krishnan Probability Score
Score 0.48959322309647
Ranking 6421/25841 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.
ExAC Score
Score 2.3390086315854E-8
Ranking 16026/18225 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
Sanders TADA Score
Score 0.93666862050785
Ranking 13271/18665 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).
Larsen Cumulative Evidence Score
Score 3
Ranking 345/461 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.
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| C12ORF26 | Methyltransferase-like protein 25 | Human | Protein Binding | 84190 | Q8N6Q8 |
| GP1BB | Platelet glycoprotein Ib beta chain | Human | Protein Binding | 2812 | P13224-2 |
| SEC11C | Signal peptidase complex catalytic subunit SEC11C | Human | Protein Binding | 90701 | Q9BY50 |
| TMEM104 | transmembrane protein 104 | Human | Protein Binding | 54868 | Q8NE00 |
| TMEM186 | Transmembrane protein 186 | Human | Protein Binding | 25880 | Q96B77 |
| TMEM231 | Transmembrane protein 231 | Human | Protein Binding | 79583 | Q9H6L2 |
| TMPPE | Transmembrane protein with metallophosphoesterase domain | Human | Protein Binding | 643853 | Q6ZT21-2 |
| UGT3A2 | UDP-glucuronosyltransferase 3A2 | Human | Protein Binding | 167127 | Q3SY77 |