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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
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

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.

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.
Original Source
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
Original Source
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).
Original Source
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.
Original Source
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.
Original Source
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