Human Gene Module / Chromosome 1 / AMPD1

AMPD1Adenosine monophosphate deaminase 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 5
Rare Variants / Common Variants
11 / 2
Aliases
AMPD1, RP5-1000E10.1,  MAD,  MADA,  MMDD
Associated Syndromes
-
Chromosome Band
1p13.2
Associated Disorders
-
Relevance to Autism

Variants in and adjacent to the AMPD1 gene were found to associate with ASD in a genome-wide assocation study using two Chinese cohorts for gene discovery and three European datasets for replication analysis (Xia et al., 2013). Case-specific functional variants in the AMPD1 gene have also been identified in ASD cases of Han Chinese descent (Zhang et al., 2014).

Molecular Function

Adenosine monophosphate deaminase 1 catalyzes the deamination of AMP to IMP in skeletal muscle and plays an important role in the purine nucleotide cycle. Deficiency of the muscle-specific enzyme is apparently a common cause of exercise-induced myopathy and probably the most common cause of metabolic myopathy in humans.

SFARI Genomic Platforms
Reports related to AMPD1 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Common genetic variants on 1p13.2 associate with risk of autism Xia K , et al. (2013) Yes -
2 Recent Recommendation AMPD1 functional variants associated with autism in Han Chinese population Zhang L , et al. (2014) Yes -
3 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
4 Support - Zhou X et al. (2022) Yes -
5 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.102G>A p.Met34Ile missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2097G>A p.Lys699%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.102G>A p.Met34Ile missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.800A>G p.Asp267Gly missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1714C>T p.Pro572Ser missense_variant De novo - Unknown 25155876 Zhang L , et al. (2014)
c.1498C>T p.Arg500Cys missense_variant Familial Paternal Unknown 25155876 Zhang L , et al. (2014)
c.1877C>G p.Ser626Cys missense_variant Familial Maternal Unknown 25155876 Zhang L , et al. (2014)
c.2042C>T p.Thr681Ile missense_variant Familial Maternal Unknown 25155876 Zhang L , et al. (2014)
c.1147G>T p.Gly383Ter stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1708C>T p.Arg570Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1889del p.Asn630IlefsTer2 frameshift_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-1625T>C Minor allele, A 2KB_upstream_variant - - - 24189344 Xia K , et al. (2013)
c.867-105C>T;c.855-105C>T Minor allele, G intron_variant - - - 24189344 Xia K , et al. (2013)
SFARI Gene score
2

Strong Candidate

Variants in and adjacent to the AMPD1 gene were found to associate with ASD in a genome-wide assocation study in two Chinese cohorts for gene discovery and three European datasets for replication analysis (Xia et al., 2013). Case-specific functional variants in the AMPD1 gene have also been identified in ASD cases of Han Chinese descent; one of these functional variants was de novo in origin (Zhang et al., 2014). A de novo frameshift variant in the AMPD1 gene was identified in an ASD proband from the Autism Sequencing Consortium (PMID 25363760).

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Variants in and adjacent to the AMPD1 gene were found to associate with ASD in a genome-wide assocation study in two Chinese cohorts for gene discovery and three European datasets for replication analysis (Xia et al., 2013). Case-specific functional variants in the AMPD1 gene have also been identified in ASD cases of Han Chinese descent; one of these functional variants was de novo in origin (Zhang et al., 2014). A de novo frameshift variant in the AMPD1 gene was identified in an ASD proband from the Autism Sequencing Consortium (PMID 25363760).

Reports Added
[New Scoring Scheme]
7/1/2015
icon
3

Increased from to 3

Description

Variants in and adjacent to the AMPD1 gene were found to associate with ASD in a genome-wide assocation study in two Chinese cohorts for gene discovery and three European datasets for replication analysis (Xia et al., 2013). Case-specific functional variants in the AMPD1 gene have also been identified in ASD cases of Han Chinese descent; one of these functional variants was de novo in origin (Zhang et al., 2014). A de novo frameshift variant in the AMPD1 gene was identified in an ASD proband from the Autism Sequencing Consortium (PMID 25363760).

Krishnan Probability Score

Score 0.45532689647746

Ranking 10042/25841 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 3.7797618503476E-12

Ranking 17259/18225 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 0.68361841423277

Ranking 1060/18665 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).
Larsen Cumulative Evidence Score

Score 24.5

Ranking 79/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score -0.15598978484197

Ranking 14311/20870 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.
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