Human Gene Module / Chromosome 10 / ADK

ADKadenosine kinase

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
1 / 2
Rare Variants / Common Variants
2 / 0
Aliases
ADK, AK
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
10q22.2
Associated Disorders
-
Relevance to Autism

A rare mutation in the ADK gene has been identified with ASD (Najmabadi et al., 2011).

Molecular Function

This gene encodes an enzyme which catalyzes the transfer of the gamma-phosphate from ATP to adenosine, thereby serving as a regulator of concentrations of both extracellular adenosine and intracellular adenine nucleotides. Adenosine has widespread effects on the cardiovascular, nervous, respiratory, and immune systems and inhibitors of the enzyme could play an important pharmacological role in increasing intravascular adenosine concentrations and acting as anti-inflammatory agents.

Reports related to ADK (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Najmabadi H , et al. (2011) Yes -
2 Support Expanding the genetic heterogeneity of intellectual disability. Anazi S , et al. (2017) No -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
A>G p.His324Arg missense_variant Familial Both parents Multiplex 21937992 Najmabadi H , et al. (2011)
c.813dup p.Asn272GlufsTer16 frameshift_variant Familial Both parents Simplex 28940097 Anazi S , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Two individuals with ASD were found in a consanguineous family homozygous for a non-synonymous variant within a region of homozygosity (LOD 5.1) (PMID 21937992). In addition, unrelated individuals were identified with a rare exonic duplication (single gene) and a rare exonic deletion (single gene) (PMID 21658581).

Score Delta: Score remained at 4

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two individuals with ASD were found in a consanguineous family homozygous for a non-synonymous variant within a region of homozygosity (LOD 5.1) (PMID 21937992). In addition, unrelated individuals were identified with a rare exonic duplication (single gene) and a rare exonic deletion (single gene) (PMID 21658581).

Reports Added
[New Scoring Scheme]
10/1/2017
4
icon
4

Decreased from 4 to 4

Description

Two individuals with ASD were found in a consanguineous family homozygous for a non-synonymous variant within a region of homozygosity (LOD 5.1) (PMID 21937992). In addition, unrelated individuals were identified with a rare exonic duplication (single gene) and a rare exonic deletion (single gene) (PMID 21658581).

7/1/2014
No data
icon
4

Increased from No data to 4

Description

Two individuals with ASD were found in a consanguineous family homozygous for a non-synonymous variant within a region of homozygosity (LOD 5.1) (PMID 21937992). In addition, unrelated individuals were identified with a rare exonic duplication (single gene) and a rare exonic deletion (single gene) (PMID 21658581).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Two individuals with ASD were found in a consanguineous family homozygous for a non-synonymous variant within a region of homozygosity (LOD 5.1) (PMID 21937992). In addition, unrelated individuals were identified with a rare exonic duplication (single gene) and a rare exonic deletion (single gene) (PMID 21658581).

Krishnan Probability Score

Score 0.32517560161623

Ranking 25346/25841 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 0.32284131424259

Ranking 6384/18225 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 0.94296174762584

Ranking 15505/18665 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 -0.5344098059943

Ranking 19513/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
FGB fibrinogen beta chain Human Protein Binding 2244 P02675
FICD Adenosine monophosphate-protein transferase FICD Human Protein Binding 11153 Q9BVA6
SRD5A3 Polyprenol reductase Human Protein Binding 79644 Q9H8P0
UBC ubiquitin C Human Protein Binding 7316 P63279
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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