Human Gene Module / Chromosome 12 / DNAH10

DNAH10Dynein, axonemal, heavy chain 10

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
8 / 10
Rare Variants / Common Variants
100 / 0
Aliases
DNAH10, hCG_1811879
Associated Syndromes
Tourette syndrome
Chromosome Band
12q24.31
Associated Disorders
-
Relevance to Autism

A de novo missense variant in this gene has been identified in a simplex ASD proband (Iossifov et al., 2012). Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family (Yuen et al., 2015). This gene was also included in a set of genes strongly enriched for those likely to affect risk (FDR < 0.30) (De Rubeis, et al., 2014).

Molecular Function

Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH10 is an inner arm dynein heavy chain

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DNAH10 (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo gene disruptions in children on the autistic spectrum Iossifov I , et al. (2012) Yes -
2 Recent Recommendation Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
3 Recent Recommendation Whole-genome sequencing of quartet families with autism spectrum disorder Yuen RK , et al. (2015) Yes -
4 Support Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
5 Positive Association De Novo Coding Variants Are Strongly Associated with Tourette Disorder Willsey AJ , et al. (2017) No -
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
7 Support De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism Cappi C , et al. (2019) No -
8 Support - Woodbury-Smith M et al. (2022) Yes -
9 Support - Zhou X et al. (2022) Yes -
10 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (100)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2648T>C p.Phe883Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
GCT>G - frameshift_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.10286C>T p.Ala3429Val missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.12008A>G p.Lys4003Arg missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.6109C>T p.Arg2037Ter stop_gained De novo - Simplex 31771860 Cappi C , et al. (2019)
c.817-1G>A - splice_site_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2131A>C p.Met711Leu missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.6109C>T p.Arg2037Ter stop_gained De novo - Simplex 28472652 Willsey AJ , et al. (2017)
c.11152+1G>C - splice_site_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2480A>T p.His827Leu missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.3076C>T p.Gln1026Ter stop_gained Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
TAA>T - frameshift_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.7466C>T p.Ser2489Phe missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.3599G>A p.Arg1200His missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.10777G>T p.Glu3593Ter stop_gained Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.12718G>T p.Glu4240Ter stop_gained Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.8946G>A p.Pro2982%3D synonymous_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.9202C>A p.Leu3068Met missense_variant De novo - Multiplex 25621899 Yuen RK , et al. (2015)
c.11887C>T p.Arg3963Cys missense_variant De novo - Multiplex 25621899 Yuen RK , et al. (2015)
c.8654C>T p.Ala2885Val missense_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.1036C>A p.Arg346Ser missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1120G>A p.Val374Met missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1172T>C p.Met391Thr missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1183G>A p.Ala395Thr missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1730C>A p.Ser577Tyr missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1742G>T p.Arg581Leu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2003C>T p.Pro668Leu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2996T>C p.Leu999Pro missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.12282C>T p.Ile4094= missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.5219_5224del p.Gly1740_Glu1741del inframe_deletion De novo - - 35982159 Zhou X et al. (2022)
c.3992C>T p.Ser1331Leu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.4268G>A p.Arg1423Gln missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.4294G>A p.Glu1432Lys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.5612T>C p.Phe1871Ser missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.6068C>T p.Ser2023Phe missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.6160G>A p.Gly2054Ser missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.6486C>G p.Asp2162Glu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.6851A>G p.Tyr2284Cys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.7657C>T p.Arg2553Cys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.8230C>T p.Arg2744Cys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.8368C>A p.Arg2790Ser missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.8525T>A p.Leu2842Gln missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.8758G>A p.Val2920Met missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.8834G>A p.Arg2945Lys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.9037C>T p.Arg3013Cys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.9308C>T p.Ala3103Val missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.11295C>G p.Gly3765%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.12780T>C p.Phe4260%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.8280+1G>T - splice_site_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.10174C>G p.Pro3392Ala missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.10228T>C p.Ser3410Pro missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.10282C>T p.Arg3428Trp missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.10537G>A p.Asp3513Asn missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.11086C>G p.Leu3696Val missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.11962G>A p.Glu3988Lys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.12211C>T p.Arg4071Trp missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.12459C>G p.Asn4153Lys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.13045C>T p.Pro4349Ser missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.817-1G>A - splice_site_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.5662C>T p.Arg1888Ter stop_gained Familial Maternal Multiplex 25621899 Yuen RK , et al. (2015)
c.1975G>T p.Gly659Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1135C>T p.Arg379Ter stop_gained Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.12718G>T p.Glu4240Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.12205C>T p.Gln4069Ter stop_gained Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.12520C>T p.Arg4174Ter stop_gained Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.12718G>T p.Glu4240Ter stop_gained Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2215C>T p.Arg739Ter stop_gained Familial Maternal Multiplex 25363760 De Rubeis S , et al. (2014)
c.2779+1G>A - splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.295G>A p.Val99Met missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.875C>T p.Ala292Val missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3430C>T p.Gln1144Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1120G>A p.Val374Met missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1120G>A p.Val374Met missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1153G>A p.Glu385Lys missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1330A>T p.Ile444Leu missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1730C>A p.Ser577Tyr missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2428G>A p.Val810Met missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.12874C>T p.Arg4292Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.3404C>A p.Thr1135Asn missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.5530G>A p.Asp1844Asn missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.5780G>A p.Arg1927His missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.6145G>A p.Val2049Ile missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.6652C>T p.Arg2218Cys missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.6751G>T p.Asp2251Tyr missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.7459C>T p.Arg2487Cys missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.7576A>G p.Met2526Val missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.7664A>T p.Lys2555Met missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.7939C>G p.Pro2647Ala missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.8230C>T p.Arg2744Cys missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.11713C>T p.Arg3905Cys missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.12091G>A p.Val4031Met missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.12136T>C p.Tyr4046His missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.12977C>T p.Ser4326Leu missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.7102C>T p.Arg2368Cys missense_variant Familial Paternal Multiplex 25363760 De Rubeis S , et al. (2014)
c.10013T>A p.Leu3338Gln missense_variant Familial Paternal Multiplex 25363760 De Rubeis S , et al. (2014)
c.10174C>G p.Pro3392Ala missense_variant Familial Paternal Multiplex 25363760 De Rubeis S , et al. (2014)
c.1493dup p.Asp498GlufsTer6 frameshift_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.13317dup p.Met4440HisfsTer8 frameshift_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.6165del p.Tyr2056ThrfsTer11 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.11042dup p.Val3682GlyfsTer101 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo missense variant that was predicted to be damaging was identified in the DNAH10 gene in a simplex ASD proband in Iossifov et al., 2012. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (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 de novo missense variant that was predicted to be damaging was identified in the DNAH10 gene in a simplex ASD proband in Iossifov et al., 2012. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

1/1/2020
3
icon
3

Decreased from 3 to 3

Description

A de novo missense variant that was predicted to be damaging was identified in the DNAH10 gene in a simplex ASD proband in Iossifov et al., 2012. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

Reports Added
[De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism.2019]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo missense variant that was predicted to be damaging was identified in the DNAH10 gene in a simplex ASD proband in Iossifov et al., 2012. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

A de novo missense variant that was predicted to be damaging was identified in the DNAH10 gene in a simplex ASD proband in Iossifov et al., 2012. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2017
icon
4

Increased from to 4

Description

A de novo missense variant that was predicted to be damaging was identified in the DNAH10 gene in a simplex ASD proband in Iossifov et al., 2012. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

Krishnan Probability Score

Score 0.48754067675295

Ranking 6950/25841 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 4.1403153457439E-37

Ranking 18194/18225 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 0.49089613862582

Ranking 429/18665 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
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