Human Gene Module / Chromosome 3 / DHX30

DHX30DExH-box helicase 30

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
6 / 12
Rare Variants / Common Variants
41 / 0
Aliases
DHX30, DDX30,  RETCOR
Associated Syndromes
-
Chromosome Band
3p21.31
Associated Disorders
ASD, EPS
Relevance to Autism

Lessel et al., 2017 identified six different de novo missense variants in the DHX30 gene in 12 unrelated individuals affected by a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, severe speech impairment, hypotonia, and gait abnormalities; in addition to these core phenotypes, seven individuals also presented with autistic features.

Molecular Function

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The family member encoded by this gene is a mitochondrial nucleoid protein that associates with mitochondrial DNA. It has also been identified as a component of a transcriptional repressor complex that functions in retinal development, and it is required to optimize the function of the zinc-finger antiviral protein.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DHX30 (12 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De Novo Missense Mutations in DHX30 Impair Global Translation and Cause a Neurodevelopmental Disorder Lessel D , et al. (2017) No Autistic features
2 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
3 Support - Hiraide T et al. (2021) No -
4 Support - Mannucci I et al. (2021) No Autistic features, stereotypy, epilepsy/seizures
5 Support - Ueda K et al. (2021) No DD, ID, autistic features
6 Support - Mahjani B et al. (2021) Yes -
7 Support - Zhou X et al. (2022) Yes -
8 Support - Alomaim MM et al. (2023) No Autistic features, stereotypy
9 Support - Sanchis-Juan A et al. (2023) Yes -
10 Support - Sheth F et al. (2023) Yes DD, ID
11 Support - Vijay Gupta et al. (2023) Yes DD
12 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (41)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - Simplex 34020708 Mannucci I et al. (2021)
c.1312C>T p.Pro438Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1478G>A p.Arg493His missense_variant De novo - - 29100085 Lessel D , et al. (2017)
c.1685A>G p.His562Arg missense_variant De novo - - 29100085 Lessel D , et al. (2017)
c.2260C>T p.Arg754Trp missense_variant De novo - - 29100085 Lessel D , et al. (2017)
c.2269C>T p.Arg757Cys missense_variant De novo - - 29100085 Lessel D , et al. (2017)
c.2342G>A p.Gly781Asp missense_variant De novo - - 29100085 Lessel D , et al. (2017)
c.2344C>T p.Arg782Trp missense_variant De novo - - 29100085 Lessel D , et al. (2017)
c.2353C>T p.Arg785Cys missense_variant De novo - - 29100085 Lessel D , et al. (2017)
c.2354G>A p.Arg785His missense_variant De novo - - 29100085 Lessel D , et al. (2017)
c.2631C>G p.Ile877Met missense_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.2174G>A p.Arg725His missense_variant Unknown - - 34020708 Mannucci I et al. (2021)
c.2353C>T p.Arg785Cys missense_variant Unknown - - 34020708 Mannucci I et al. (2021)
c.1846-1G>T - splice_site_variant De novo - Simplex 38025430 Vijay Gupta et al. (2023)
c.2218C>T p.Arg740Cys missense_variant Unknown - - 39039281 Axel Schmidt et al. (2024)
c.2345G>A p.Arg782Gln missense_variant De novo - Simplex 34145223 Ueda K et al. (2021)
c.2353C>T p.Arg785Cys missense_variant De novo - Simplex 34145223 Ueda K et al. (2021)
c.2354G>A p.Arg785His missense_variant De novo - Simplex 34145223 Ueda K et al. (2021)
c.1317T>G p.His439Gln missense_variant Unknown - Simplex 37543562 Sheth F et al. (2023)
c.2389C>T p.Arg797Ter stop_gained Familial Maternal - 34020708 Mannucci I et al. (2021)
c.2353C>T p.Arg785Cys missense_variant De novo - Simplex 33644862 Hiraide T et al. (2021)
c.1385G>A p.Gly462Glu missense_variant De novo - Simplex 34020708 Mannucci I et al. (2021)
c.1478G>A p.Arg493His missense_variant Unknown - Simplex 34020708 Mannucci I et al. (2021)
c.1685A>G p.His562Arg missense_variant Unknown - Simplex 34020708 Mannucci I et al. (2021)
c.2201C>A p.Ala734Asp missense_variant De novo - Simplex 34020708 Mannucci I et al. (2021)
c.2260C>T p.Arg754Trp missense_variant De novo - Simplex 34020708 Mannucci I et al. (2021)
c.2261G>A p.Arg754Gln missense_variant De novo - Simplex 34020708 Mannucci I et al. (2021)
c.2269C>T p.Arg757Cys missense_variant De novo - Simplex 34020708 Mannucci I et al. (2021)
c.2344C>T p.Arg782Trp missense_variant De novo - Simplex 34020708 Mannucci I et al. (2021)
c.2345G>A p.Arg782Gln missense_variant De novo - Simplex 34020708 Mannucci I et al. (2021)
c.2353C>T p.Arg785Cys missense_variant De novo - Simplex 34020708 Mannucci I et al. (2021)
c.2354G>A p.Arg785His missense_variant De novo - Simplex 34020708 Mannucci I et al. (2021)
c.2723G>A p.Arg908Gln missense_variant De novo - Simplex 34020708 Mannucci I et al. (2021)
c.2387C>T p.Pro796Leu missense_variant De novo - Simplex 36643085 Alomaim MM et al. (2023)
c.1685A>G p.His562Arg missense_variant Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.1022C>T p.Thr341Ile missense_variant Familial Maternal Simplex 37543562 Sheth F et al. (2023)
c.1186C>G p.Arg396Gly missense_variant Familial Paternal Simplex 37543562 Sheth F et al. (2023)
c.2344C>T p.Arg782Trp missense_variant Familial Maternal Multiplex 34020708 Mannucci I et al. (2021)
c.2215A>G p.Thr739Ala missense_variant Unknown Not maternal Simplex 34020708 Mannucci I et al. (2021)
c.347_360del p.Ala116ValfsTer12 frameshift_variant De novo - Simplex 34020708 Mannucci I et al. (2021)
c.2491+2dup - frameshift_variant Familial Maternal Multiplex (monozygotic twins) 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Lessel et al., 2017 identified six different de novo missense variants in the DHX30 gene in 12 unrelated individuals affected by a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, severe speech impairment, and gait abnormalities; in addition to these core phenotypes, seven individuals also presented with autistic features.

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2021
S
icon
S

Score remained at S

Description

Lessel et al., 2017 identified six different de novo missense variants in the DHX30 gene in 12 unrelated individuals affected by a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, severe speech impairment, and gait abnormalities; in addition to these core phenotypes, seven individuals also presented with autistic features.

Reports Added
[Genotype-phenotype correlations and novel molecular insights into the DHX30-associated neurodevelopmental disorders2021]
1/1/2021
S
icon
S

Score remained at S

Description

Lessel et al., 2017 identified six different de novo missense variants in the DHX30 gene in 12 unrelated individuals affected by a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, severe speech impairment, and gait abnormalities; in addition to these core phenotypes, seven individuals also presented with autistic features.

Reports Added
[Genetic and phenotypic analysis of 101 patients with developmental delay or intellectual disability using whole-exome sequencing2021]
10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Lessel et al., 2017 identified six different de novo missense variants in the DHX30 gene in 12 unrelated individuals affected by a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, severe speech impairment, and gait abnormalities; in addition to these core phenotypes, seven individuals also presented with autistic features.

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

Score remained at S

Description

Lessel et al., 2017 identified six different de novo missense variants in the DHX30 gene in 12 unrelated individuals affected by a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, severe speech impairment, and gait abnormalities; in addition to these core phenotypes, seven individuals also presented with autistic features.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
Krishnan Probability Score

Score 0.49168525159545

Ranking 5242/25841 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 0.99999946256976

Ranking 269/18225 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 0.92995325267621

Ranking 11301/18665 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 0.37243955370986

Ranking 1761/20870 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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