Human Gene Module / Chromosome 1 / CPT2

CPT2carnitine palmitoyltransferase 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 5
Rare Variants / Common Variants
10 / 0
Aliases
CPT2, CPT1,  CPTASE,  IIAE4
Associated Syndromes
-
Chromosome Band
1p32.3
Associated Disorders
-
Relevance to Autism

Targeted sequencing of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified a de novo damaging missense variant, two inherited loss-of-function variants, and an inherited damaging missense variant in the CPT2 gene in ASD probands. Transmission and De Novo Association (TADA) analysis of this cohort of Chinese ASD cases and controls in Guo et al., 2017 identified the CPT2 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.001483); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

Molecular Function

The protein encoded by this gene is a nuclear protein which is transported to the mitochondrial inner membrane. Together with carnitine palmitoyltransferase I, the encoded protein oxidizes long-chain fatty acids in the mitochondria. Defects in this gene are associated with mitochondrial long-chain fatty-acid (LCFA) oxidation disorders.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CPT2 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) Yes -
2 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
3 Support - Zhou X et al. (2022) Yes -
4 Support - Balasar et al. (2023) Yes -
5 Support - Omri Bar et al. (2024) Yes OCD, learning disability
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.499C>T p.Arg167Trp missense_variant Familial - - 28831199 Li J , et al. (2017)
c.1547T>C p.Phe516Ser missense_variant De novo - - 28831199 Li J , et al. (2017)
c.180C>T p.Thr60%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.852del p.Glu285SerfsTer7 frameshift_variant Familial - - 28831199 Li J , et al. (2017)
c.1049G>A p.Arg350His missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1613del p.Tyr538SerfsTer5 frameshift_variant Familial - - 28831199 Li J , et al. (2017)
c.338C>T p.Ser113Leu missense_variant Unknown - Simplex 37524782 Balasar et al. (2023)
c.867A>G p.Ala289= synonymous_variant De novo - Simplex 29346770 Takata A , et al. (2018)
c.1342T>C p.Phe448Leu missense_variant Familial Maternal Simplex 38256266 Omri Bar et al. (2024)
c.1239_1240del p.Lys414ThrfsTer7 frameshift_variant Familial Maternal Simplex 38256266 Omri Bar et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Targeted sequencing of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified a de novo damaging missense variant, two inherited loss-of-function variants, and an inherited damaging missense variant in the CPT2 gene in ASD probands. Transmission and De Novo Association (TADA) analysis of this cohort of Chinese ASD cases and controls identified the CPT2 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.001483); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

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

Targeted sequencing of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified a de novo damaging missense variant, two inherited loss-of-function variants, and an inherited damaging missense variant in the CPT2 gene in ASD probands. Transmission and De Novo Association (TADA) analysis of this cohort of Chinese ASD cases and controls identified the CPT2 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.001483); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Targeted sequencing of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified a de novo damaging missense variant, two inherited loss-of-function variants, and an inherited damaging missense variant in the CPT2 gene in ASD probands. Transmission and De Novo Association (TADA) analysis of this cohort of Chinese ASD cases and controls identified the CPT2 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.001483); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

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

Increased from to 4

Description

Targeted sequencing of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified a de novo damaging missense variant, two inherited loss-of-function variants, and an inherited damaging missense variant in the CPT2 gene in ASD probands. Transmission and De Novo Association (TADA) analysis of this cohort of Chinese ASD cases and controls identified the CPT2 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.001483); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

Krishnan Probability Score

Score 0.29809620191546

Ranking 25483/25841 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 4.7717807538114E-7

Ranking 15266/18225 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 0.94199564808343

Ranking 15140/18665 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 -0.59680733179606

Ranking 19872/20870 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
Submit New Gene

Report an Error