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
3
Suggestive Evidence
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 criteriaThe literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.
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 |