AGMOalkylglycerol monooxygenase
Autism Reports / Total Reports
8 / 8Rare Variants / Common Variants
14 / 0Aliases
AGMO, tcag7.1136, TMEM195Associated Syndromes
-Chromosome Band
7p21.2Associated Disorders
-Relevance to Autism
A rare CNV in the AGMO (TMEM195) gene has been identified with autism in AGRE, NIMH and additional cohorts (Sebat et al., 2007).
Molecular Function
The protein encoded by this gene is a tetrahydrobiopterin- and iron-dependent enzyme that cleaves the ether bond of alkylglycerols. Sequence comparisons distinguish this protein as forming a third, distinct class of tetrahydrobiopterin-dependent enzymes.
External Links
SFARI Genomic Platforms
Reports related to AGMO (8 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Primary | Strong association of de novo copy number mutations with autism | Sebat J , et al. (2007) | Yes | - |
| 2 | Support | Direct measure of the de novo mutation rate in autism and schizophrenia cohorts | Awadalla P , et al. (2010) | Yes | - |
| 3 | Support | A discovery resource of rare copy number variations in individuals with autism spectrum disorder | Prasad A , et al. (2013) | Yes | - |
| 4 | Support | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
| 5 | Support | Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior | Doan RN , et al. (2016) | Yes | - |
| 6 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
| 7 | Support | Segregating patterns of copy number variations in extended autism spectrum disorder (ASD) pedigrees | Woodbury-Smith M et al. (2020) | Yes | - |
| 8 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
Rare Variants (14)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | De novo | - | Simplex | 17363630 | Sebat J , et al. (2007) | |
| - | - | copy_number_loss | Unknown | - | Unknown | 23275889 | Prasad A , et al. (2013) | |
| c.1263+13066del | - | intron_variant | - | - | Unknown | 27667684 | Doan RN , et al. (2016) | |
| c.835T>C | p.Phe279Leu | missense_variant | De novo | - | - | 20797689 | Awadalla P , et al. (2010) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 32372567 | Woodbury-Smith M et al. (2020) | |
| c.473C>T | p.Thr158Ile | missense_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.822+2T>C | - | splice_site_variant | Familial | Maternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
| c.1213C>T | p.Arg405Ter | stop_gained | Familial | Paternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
| c.677-1G>C | - | splice_site_variant | Familial | Maternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| c.1213C>T | p.Arg405Ter | stop_gained | Familial | Paternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| c.842dup | p.Trp282MetfsTer13 | frameshift_variant | Familial | Paternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
| c.920_921insG | p.Lys308Ter | frameshift_variant | Familial | Maternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| c.1016_1017del | p.Thr339SerfsTer12 | frameshift_variant | Familial | Maternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| c.1314_1315insA | p.Leu439ThrfsTer10 | 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 variant was observed in one affected individual in a single study (Sebat et al., 2007).
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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
2
Decreased from 3 to 2
Description
A de novo variant was observed in one affected individual in a single study (Sebat et al., 2007).
4/1/2020
3
3
Decreased from 3 to 3
Description
A de novo variant was observed in one affected individual in a single study (Sebat et al., 2007).
10/1/2019
4
3
Decreased from 4 to 3
New Scoring Scheme
Description
A de novo variant was observed in one affected individual in a single study (Sebat et al., 2007).
Reports Added
[New Scoring Scheme]7/1/2019
4
4
Decreased from 4 to 4
Description
A de novo variant was observed in one affected individual in a single study (Sebat et al., 2007).
10/1/2016
4
4
Decreased from 4 to 4
Description
A de novo variant was observed in one affected individual in a single study (Sebat et al., 2007).
1/1/2016
4
4
Decreased from 4 to 4
Description
A de novo variant was observed in one affected individual in a single study (Sebat et al., 2007).
Reports Added
[Strong association of de novo copy number mutations with autism.2007] [Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.2010] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014]7/1/2014
No data
4
Increased from No data to 4
Description
A de novo variant was observed in one affected individual in a single study (Sebat et al., 2007).
4/1/2014
No data
4
Increased from No data to 4
Description
A de novo variant was observed in one affected individual in a single study (Sebat et al., 2007).
Krishnan Probability Score
Score 0.44723938649654
Ranking 13614/25841 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 3.2579268842573E-7
Ranking 15375/18225 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 0.94498636349261
Ranking 16291/18665 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 1
Ranking 412/461 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 -0.30814914875571
Ranking 17324/20870 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.