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

SFARI Genomic Platforms
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

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).

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).

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).

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.
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
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).
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.
Submit New Gene

Report an Error