Human Gene Module / Chromosome 1 / SCP2

SCP2sterol carrier protein 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
4 / 0
Aliases
SCP2, NLTP,  NSL-TP,  SCP-2,  SCP-CHI,  SCP-X,  SCPX
Associated Syndromes
-
Chromosome Band
1p32.3
Associated Disorders
-
Relevance to Autism

A de novo frameshift variant in the SCP2 gene was identified in an ASD proband from the Simons Simplex Collection in Sanders et al., 2012. Targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls detected rare inherited loss-of-function and damaging missense variants in Chinese ASD probands in Guo et al., 2017. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of Chinese ASD cases and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified SCP2 as an ASD candidate gene with a PTADA of 0.003421.

Molecular Function

This gene encodes two proteins: sterol carrier protein X (SCPx) and sterol carrier protein 2 (SCP2), as a result of transcription initiation from 2 independently regulated promoters. The transcript initiated from the proximal promoter encodes the longer SCPx protein, and the transcript initiated from the distal promoter encodes the shorter SCP2 protein, with the 2 proteins sharing a common C-terminus. Evidence suggests that the SCPx protein is a peroxisome-associated thiolase that is involved in the oxidation of branched chain fatty acids, while the SCP2 protein is thought to be an intracellular lipid transfer protein. This gene is highly expressed in organs involved in lipid metabolism, and may play a role in Zellweger syndrome, in which cells are deficient in peroxisomes and have impaired bile acid synthesis.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SCP2 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo mutations revealed by whole-exome sequencing are strongly associated with autism Sanders SJ , et al. (2012) Yes -
2 Recent Recommendation Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) Yes -
3 Support - Zhou X et al. (2022) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.542+1G>C - splice_site_variant Familial - - 28831199 Li J , et al. (2017)
c.543-7C>G - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
c.943G>A p.Ala315Thr missense_variant Familial - - 28831199 Li J , et al. (2017)
c.199+2757_199+2758dup - frameshift_variant De novo - Simplex 22495306 Sanders SJ , et al. (2012)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo frameshift variant in the SCP2 gene was identified in an ASD proband from the Simons Simplex Collection in Sanders et al., 2012. Targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls detected rare inherited loss-of-function and damaging missense variants in Chinese ASD probands in Guo et al., 2017. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of Chinese ASD cases and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified SCP2 as an ASD candidate gene with a PTADA of 0.003421.

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 frameshift variant in the SCP2 gene was identified in an ASD proband from the Simons Simplex Collection in Sanders et al., 2012. Targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls detected rare inherited loss-of-function and damaging missense variants in Chinese ASD probands in Guo et al., 2017. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of Chinese ASD cases and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified SCP2 as an ASD candidate gene with a PTADA of 0.003421.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo frameshift variant in the SCP2 gene was identified in an ASD proband from the Simons Simplex Collection in Sanders et al., 2012. Targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls detected rare inherited loss-of-function and damaging missense variants in Chinese ASD probands in Guo et al., 2017. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of Chinese ASD cases and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified SCP2 as an ASD candidate gene with a PTADA of 0.003421.

Reports Added
[New Scoring Scheme]
7/1/2017
icon
4

Increased from to 4

Description

A de novo frameshift variant in the SCP2 gene was identified in an ASD proband from the Simons Simplex Collection in Sanders et al., 2012. Targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls detected rare inherited loss-of-function and damaging missense variants in Chinese ASD probands in Guo et al., 2017. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of Chinese ASD cases and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified SCP2 as an ASD candidate gene with a PTADA of 0.003421.

Krishnan Probability Score

Score 0.32881410529578

Ranking 25073/25841 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 0.0001397596286967

Ranking 12907/18225 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 0.5497764066191

Ranking 564/18665 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 -0.14562993365264

Ranking 13992/20870 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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