Human Gene Module / Chromosome 2 / DPP4

DPP4Dipeptidyl-peptidase 4

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
3 / 2
Aliases
DPP4, ADABP,  ADCP2,  CD26,  DPPIV,  TP103
Associated Syndromes
-
Chromosome Band
2q24.2
Associated Disorders
-
Relevance to Autism

A recurrent homozygous splice-site variant in the DPP4 gene was found to segregate with ASD in one out of two multiplex families (Lim et al., 2013). A de novo frameshift variant in the DPP4 gene has also been identified (De Rubeis et al., 2014).

Molecular Function

The protein encoded by this gene is identical to adenosine deaminase complexing protein-2, and to the T-cell activation antigen CD26. It is an intrinsic membrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DPP4 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
2 Primary Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders Lim ET , et al. (2013) Yes -
3 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
4 Recent Recommendation De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia Takata A , et al. (2016) No -
5 Positive Association Novel genetic loci associated with hippocampal volume Hibar DP , et al. (2017) No -
6 Positive Association Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1890A>G p.Ser630= synonymous_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.668dup p.Leu223PhefsTer7 frameshift_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.95-2A>G - splice_site_variant Familial Both parents Multiplex 23352160 Lim ET , et al. (2013)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.1568-823G>A;c.1565-823G>A - intron_variant - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
c.2053-4266G>A;c.2050-4266G>A - intron_variant - - - 28098162 Hibar DP , et al. (2017)
SFARI Gene score
2

Strong Candidate

A recurrent homozygous splice-site variant in the DPP4 gene was found to segregate with ASD in one out of two multiplex families (Lim et al., 2013). A de novo frameshift variant in the DPP4 gene has also been identified (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 recurrent homozygous splice-site variant in the DPP4 gene was found to segregate with ASD in one out of two multiplex families (Lim et al., 2013). A de novo frameshift variant in the DPP4 gene has also been identified (De Rubeis et al., 2014).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A recurrent homozygous splice-site variant in the DPP4 gene was found to segregate with ASD in one out of two multiplex families (Lim et al., 2013). A de novo frameshift variant in the DPP4 gene has also been identified (De Rubeis et al., 2014).

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

Decreased from 4 to 4

Description

A recurrent homozygous splice-site variant in the DPP4 gene was found to segregate with ASD in one out of two multiplex families (Lim et al., 2013). A de novo frameshift variant in the DPP4 gene has also been identified (De Rubeis et al., 2014).

Reports Added
[Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia.2016] [Novel genetic loci associated with hippocampal volume.2017] [Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with ...2017]
1/1/2017
4
icon
4

Decreased from 4 to 4

Description

A recurrent homozygous splice-site variant in the DPP4 gene was found to segregate with ASD in one out of two multiplex families (Lim et al., 2013). A de novo frameshift variant in the DPP4 gene has also been identified (De Rubeis et al., 2014).

Reports Added
[Novel genetic loci associated with hippocampal volume.2017]
4/1/2016
4
icon
4

Decreased from 4 to 4

Description

A recurrent homozygous splice-site variant in the DPP4 gene was found to segregate with ASD in one out of two multiplex families (Lim et al., 2013). A de novo frameshift variant in the DPP4 gene has also been identified (De Rubeis et al., 2014).

Reports Added
[Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia.2016]
7/1/2015
icon
4

Increased from to 4

Description

A recurrent homozygous splice-site variant in the DPP4 gene was found to segregate with ASD in one out of two multiplex families (Lim et al., 2013). A de novo frameshift variant in the DPP4 gene has also been identified (De Rubeis et al., 2014).

Krishnan Probability Score

Score 0.44727462527216

Ranking 13218/25841 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 4.0574053944884E-10

Ranking 16740/18225 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 0.71708623850646

Ranking 1273/18665 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 0.16974075341186

Ranking 4814/20870 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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