Human Gene Module / Chromosome 2 / DPP10

DPP10Dipeptidyl-peptidase 10

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 13
Rare Variants / Common Variants
11 / 0
Aliases
DPP10, DPL2,  DPPY,  DPRP3
Associated Syndromes
-
Chromosome Band
2q14.1
Associated Disorders
-
Relevance to Autism

Rare mutations in the DPP10 gene have been identified with autism (Marshall et al., 2008).

Molecular Function

Binds specific voltage-gated potassium channels and alters their expression and biophysical properties

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DPP10 (13 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase 10 (DPP10) Jerng HH , et al. (2004) No -
2 Recent Recommendation DPP10 is an inactivation modulatory protein of Kv4.3 and Kv1.4 Li HL , et al. (2006) No -
3 Primary Structural variation of chromosomes in autism spectrum disorder Marshall CR , et al. (2008) Yes -
4 Recent Recommendation Ternary Kv4.2 channels recapitulate voltage-dependent inactivation kinetics of A-type K+ channels in cerebellar granule neurons Amarillo Y , et al. (2008) No -
5 Recent Recommendation Weighing the evidence for a ternary protein complex mediating A-type K+ currents in neurons Maffie J and Rudy B (2008) No -
6 Recent Recommendation Augmentation of Kv4.2-encoded currents by accessory dipeptidyl peptidase 6 and 10 subunits reflects selective cell surface Kv4.2 protein stabilization Foeger NC , et al. (2012) No -
7 Recent Recommendation Human-specific histone methylation signatures at transcription start sites in prefrontal neurons Shulha HP , et al. (2012) No -
8 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
9 Support Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder Girirajan S , et al. (2013) Yes -
10 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
11 Negative Association Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10 Mak ASL , et al. (2017) Yes -
12 Support - Zhou X et al. (2022) Yes -
13 Support - Wang J et al. (2023) Yes -
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Unknown - - 28670437 Mak ASL , et al. (2017)
- - copy_number_gain Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_loss Unknown - Unknown 23275889 Prasad A , et al. (2013)
c.556-10961A>T - intron_variant - - Unknown 27667684 Doan RN , et al. (2016)
c.1408T>C p.Tyr470His missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss Familial Paternal Simplex 18252227 Marshall CR , et al. (2008)
- - copy_number_gain Familial Maternal Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_gain Familial Paternal Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_gain Familial Paternal Multiplex 18252227 Marshall CR , et al. (2008)
c.188C>T p.Ser63Phe missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.443C>T p.Ser148Leu missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

An inherited gain in one family and an inherited loss in a second was reported in Marshall et al., 2008 out of a total of 427 unrelated ASD probands that were screened. Similar events were not seen in 500 controls or DGV controls (N ~1000 at time of analysis). DPP10 was found to be enriched for exon-disrupting CNVs in a case-control study in Girirajan et al., 2013 (5 exon-disrupting duplications in 2,588 cases compared to none in 2670 controls; P=0.029).

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.

7/1/2020
2
icon
2

Score remained at 2

Description

An inherited gain in one family and an inherited loss in a second was reported in Marshall et al., 2008 out of a total of 427 unrelated ASD probands that were screened. Similar events were not seen in 500 controls or DGV controls (N ~1000 at time of analysis). DPP10 was found to be enriched for exon-disrupting CNVs in a case-control study in Girirajan et al., 2013 (5 exon-disrupting duplications in 2,588 cases compared to none in 2670 controls; P=0.029).

Reports Added
[Clustering by phenotype and genome-wide association study in autism2020]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

An inherited gain in one family and an inherited loss in a second was reported in Marshall et al., 2008 out of a total of 427 unrelated ASD probands that were screened. Similar events were not seen in 500 controls or DGV controls (N ~1000 at time of analysis). DPP10 was found to be enriched for exon-disrupting CNVs in a case-control study in Girirajan et al., 2013 (5 exon-disrupting duplications in 2,588 cases compared to none in 2670 controls; P=0.029).

Reports Added
[New Scoring Scheme]
7/1/2017
3
icon
3

Decreased from 3 to 3

Description

An inherited gain in one family and an inherited loss in a second was reported in Marshall et al., 2008 out of a total of 427 unrelated ASD probands that were screened. Similar events were not seen in 500 controls or DGV controls (N ~1000 at time of analysis). DPP10 was found to be enriched for exon-disrupting CNVs in a case-control study in Girirajan et al., 2013 (5 exon-disrupting duplications in 2,588 cases compared to none in 2670 controls; P=0.029).

Reports Added
[Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10.2017]
10/1/2016
3
icon
3

Decreased from 3 to 3

Description

An inherited gain in one family and an inherited loss in a second was reported in Marshall et al., 2008 out of a total of 427 unrelated ASD probands that were screened. Similar events were not seen in 500 controls or DGV controls (N ~1000 at time of analysis). DPP10 was found to be enriched for exon-disrupting CNVs in a case-control study in Girirajan et al., 2013 (5 exon-disrupting duplications in 2,588 cases compared to none in 2670 controls; P=0.029).

Reports Added
[Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016]
4/1/2016
4
icon
3

Decreased from 4 to 3

Description

An inherited gain in one family and an inherited loss in a second was reported in Marshall et al., 2008 out of a total of 427 unrelated ASD probands that were screened. Similar events were not seen in 500 controls or DGV controls (N ~1000 at time of analysis). DPP10 was found to be enriched for exon-disrupting CNVs in a case-control study in Girirajan et al., 2013 (5 exon-disrupting duplications in 2,588 cases compared to none in 2670 controls; P=0.029).

7/1/2014
No data
icon
4

Increased from No data to 4

Description

An inherited gain in one family and an inherited loss in a second was reported (out of 427 unrelated individuals screened). Similar events were not seen in 500 controls or DGV controls (N ~1000 at time of analysis).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

An inherited gain in one family and an inherited loss in a second was reported (out of 427 unrelated individuals screened). Similar events were not seen in 500 controls or DGV controls (N ~1000 at time of analysis).

Krishnan Probability Score

Score 0.53256949826715

Ranking 1518/25841 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 0.99998928551057

Ranking 461/18225 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 0.9500734407594

Ranking 18347/18665 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 0.3453218486633

Ranking 2079/20870 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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