Human Gene Module / Chromosome 12 / SLCO1B3

SLCO1B3Solute carrier organic anion transporter family, member 1B3

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 6
Rare Variants / Common Variants
21 / 0
Aliases
SLCO1B3, HBLRR,  LST-2,  LST-3TM13,  LST3,  OATP-8,  OATP1B3,  OATP8,  SLC21A8
Associated Syndromes
-
Chromosome Band
12p12.2
Associated Disorders
-
Relevance to Autism

A de novo splice-site variant in this gene has been identified in a simplex ASD proband (De Rubeis et al., 2014). Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family (Yuen et al., 2015). This gene was also included in a set of genes strongly enriched for those likely to affect risk (FDR < 0.30) (De Rubeis, et al., 2014).

Molecular Function

This gene encodes a liver-specific member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of endogenous and xenobiotic compounds and plays a critical role in bile acid and bilirubin transport. Mutations in this gene are a cause of Rotor type hyperbilirubinemia (OMIM:237450).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SLCO1B3 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Recent Recommendation Whole-genome sequencing of quartet families with autism spectrum disorder Yuen RK , et al. (2015) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Support Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort Wu H , et al. (2019) Yes Macrocephaly
5 Support - Zhou X et al. (2022) Yes -
6 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (21)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1980C>T p.Asp660%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.970+1G>A - splice_site_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.1960A>G p.Lys654Glu missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.781G>A p.Gly261Ser missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1165G>A p.Gly389Arg missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1252T>C p.Ser418Pro missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1342G>A p.Val448Met missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1135+1G>A - missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1747+1G>A - missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.428T>A p.Leu143Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1413+1G>A - splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1663+1G>A - splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1397A>G p.Asp466Gly missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1615G>C p.Ala539Pro missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1696G>A p.Glu566Lys missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1696G>A p.Glu566Lys missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1082A>G p.Lys361Arg missense_variant Familial Maternal Multiplex 25363760 De Rubeis S , et al. (2014)
c.508_509del p.Met170ValfsTer27 frameshift_variant Familial Maternal Simplex 31674007 Wu H , et al. (2019)
c.121_125dup p.Asp42GlufsTer13 frameshift_variant Familial Maternal Multiplex 25621899 Yuen RK , et al. (2015)
c.852_855del p.Lys285HisfsTer14 frameshift_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1794_1795del p.Cys599TyrfsTer15 frameshift_variant Familial Maternal Multiplex 25621899 Yuen RK , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo splice-site variant in the SLCO1B3 gene was identified in a simplex ASD proband in De Rubeis et al., 2014. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

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

A de novo splice-site variant in the SLCO1B3 gene was identified in a simplex ASD proband in De Rubeis et al., 2014. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo splice-site variant in the SLCO1B3 gene was identified in a simplex ASD proband in De Rubeis et al., 2014. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

Reports Added
[Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.2019] [New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

A de novo splice-site variant in the SLCO1B3 gene was identified in a simplex ASD proband in De Rubeis et al., 2014. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2017
icon
4

Increased from to 4

Description

A de novo splice-site variant in the SLCO1B3 gene was identified in a simplex ASD proband in De Rubeis et al., 2014. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

Krishnan Probability Score

Score 0.46457562107462

Ranking 9205/25841 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 9.2410806621178E-17

Ranking 17795/18225 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 0.28619924339527

Ranking 169/18665 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
Zhang D Score

Score -0.032536716340566

Ranking 9779/20870 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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