Human Gene Module / Chromosome 3 / HTR3C

HTR3C5-hydroxytryptamine (serotonin) receptor 3, family member C

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 6
Rare Variants / Common Variants
5 / 3
Aliases
-
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
3q27.1
Associated 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

Reports related to HTR3C (6 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 -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.78C>T p.Asp26%3D 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.870C>T p.Asn290%3D synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
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: Decreased from 4 to 3

3

Suggestive Evidence

See all Category 3 Genes

The 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.

10/1/2019
4
icon
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
icon
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
icon
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
icon
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.
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
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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