AGAP1ArfGAP with GTPase domain, ankyrin repeat and PH domain 1
Autism Reports / Total Reports
4 / 10Rare Variants / Common Variants
16 / 0Aliases
AGAP1, AGAP-1, CENTG2, GGAP1, cnt-g2Associated Syndromes
-Chromosome Band
2q37.2Associated Disorders
-Relevance to Autism
Rare variants in the AGAP1 gene have been identified with autism (Wassink et al., 2005).
Molecular Function
This gene encodes a member of an ADP-ribosylation factor GTPase-activating protein family involved in membrane trafficking and cytoskeleton dynamics. This gene functions as a direct regulator of the adaptor-related protein complex 3 on endosomes.
External Links
SFARI Genomic Platforms
Reports related to AGAP1 (10 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | AGAP1, an endosome-associated, phosphoinositide-dependent ADP-ribosylation factor GTPase-activating protein that affects actin cytoskeleton | Nie Z , et al. (2002) | No | - |
| 2 | Recent Recommendation | AGAP1, a novel binding partner of nitric oxide-sensitive guanylyl cyclase | Meurer S , et al. (2004) | No | - |
| 3 | Primary | Evaluation of the chromosome 2q37.3 gene CENTG2 as an autism susceptibility gene | Wassink TH , et al. (2005) | Yes | - |
| 4 | Recent Recommendation | Mutational analysis of the Arf1*GTP/Arf GAP interface reveals an Arf1 mutant that selectively affects the Arf GAP ASAP1 | Luo R , et al. (2005) | No | - |
| 5 | Support | Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders | Cukier HN , et al. (2014) | Yes | - |
| 6 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 7 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | No | - |
| 8 | Recent Recommendation | The Endosome Localized Arf-GAP AGAP1 Modulates Dendritic Spine Morphology Downstream of the Neurodevelopmental Disorder Factor Dysbindin | Arnold M , et al. (2016) | No | - |
| 9 | Support | - | Zhou X et al. (2022) | Yes | - |
| 10 | Support | - | Lewis SA et al. (2023) | No | ASD, ID |
Rare Variants (16)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | De novo | - | - | 37470098 | Lewis SA et al. (2023) | |
| - | - | copy_number_loss | De novo | - | - | 15892143 | Wassink TH , et al. (2005) | |
| - | - | copy_number_loss | Familial | Maternal | - | 37470098 | Lewis SA et al. (2023) | |
| - | - | copy_number_loss | Familial | Paternal | - | 37470098 | Lewis SA et al. (2023) | |
| - | - | copy_number_loss | Familial | Maternal | - | 15892143 | Wassink TH , et al. (2005) | |
| c.1222T>C | p.(=) | synonymous_variant | - | - | - | 15892143 | Wassink TH , et al. (2005) | |
| c.539-7G>T | - | splice_region_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.818A>G | p.Ser83Gly | missense_variant | - | - | - | 15892143 | Wassink TH , et al. (2005) | |
| c.2393G>A | p.Arg798Gln | missense_variant | - | - | - | 15892143 | Wassink TH , et al. (2005) | |
| - | - | copy_number_loss | Familial | Paternal | Multiplex | 15892143 | Wassink TH , et al. (2005) | |
| c.2972C>A | p.Pro801Thr | missense_variant | Familial | - | - | 15892143 | Wassink TH , et al. (2005) | |
| c.2309G>A | p.Arg770His | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.1451C>A | p.Ala484Asp | synonymous_variant | Familial | Paternal | - | 15892143 | Wassink TH , et al. (2005) | |
| c.1804C>T | p.Arg602Trp | synonymous_variant | Familial | Maternal | Multiplex | 15892143 | Wassink TH , et al. (2005) | |
| c.570C>T | p.Ile190= | synonymous_variant | De novo | - | Unknown | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.574G>A | p.Asp192Asn | missense_variant | Familial | - | Extended multiplex (at least one pair of ASD affec | 24410847 | Cukier HN , et al. (2014) |
Common Variants
No common variants reported.
SFARI Gene score
2
Strong Candidate
Single publication showing several rare mutations in autism families (PMID: 15892143). Some contradictory linkage findings.
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
Single publication showing several rare mutations in autism families (PMID: 15892143). Some contradictory linkage findings.
10/1/2019
4
3
Decreased from 4 to 3
New Scoring Scheme
Description
Single publication showing several rare mutations in autism families (PMID: 15892143). Some contradictory linkage findings.
Reports Added
[New Scoring Scheme]10/1/2016
4
4
Decreased from 4 to 4
Description
Single publication showing several rare mutations in autism families (PMID: 15892143). Some contradictory linkage findings.
1/1/2016
4
4
Decreased from 4 to 4
Description
Single publication showing several rare mutations in autism families (PMID: 15892143). Some contradictory linkage findings.
Reports Added
[Evaluation of the chromosome 2q37.3 gene CENTG2 as an autism susceptibility gene.2005] [Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [AGAP1, an endosome-associated, phosphoinositide-dependent ADP-ribosylation factor GTPase-activating protein that affects actin cytoskeleton.2002] [AGAP1, a novel binding partner of nitric oxide-sensitive guanylyl cyclase.2004] [Mutational analysis of the Arf1*GTP/Arf GAP interface reveals an Arf1 mutant that selectively affects the Arf GAP ASAP1.2005] [The contribution of de novo coding mutations to autism spectrum disorder2014]1/1/2015
4
4
Decreased from 4 to 4
Description
Single publication showing several rare mutations in autism families (PMID: 15892143). Some contradictory linkage findings.
7/1/2014
No data
4
Increased from No data to 4
Description
Single publication showing several rare mutations in autism families (PMID: 15892143). Some contradictory linkage findings.
4/1/2014
No data
4
Increased from No data to 4
Description
Single publication showing several rare mutations in autism families (PMID: 15892143). Some contradictory linkage findings.
Krishnan Probability Score
Score 0.571028831339
Ranking 833/25841 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 0.9993564357408
Ranking 982/18225 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 0.8450560258208
Ranking 3293/18665 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 3
Ranking 328/461 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 0.36080221706176
Ranking 1892/20870 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.
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| ARF1 | ADP-ribosylation factor 1 | Human | Direct Regulation | 375 | Q8N6T3 |
| CBWD1 | COBW domain containing 1 | Human | Protein Binding | 55871 | Q9BRT8 |
| Chrm5 | cholinergic receptor, muscarinic 5 | Rat | Protein Binding | 53949 | P08911 |
| EPHA7 | EPH receptor A7 | Human | Protein Binding | 2045 | Q15375 |
| FLCN | folliculin | Human | Protein Binding | 201163 | Q8NFG4 |
| GUCY1A3 | guanylate cyclase 1, soluble, alpha 3 | Human | Protein Binding | 2982 | Q02108 |
| GUCY1B3 | guanylate cyclase 1, soluble, beta 3 | Human | Protein Binding | 2983 | Q02153 |
| LZTS2 | leucine zipper, putative tumor suppressor 2 | Human | Protein Binding | 84445 | Q9BRK4 |
| MIB1 | mindbomb E3 ubiquitin protein ligase 1 | Rat | Protein Binding | 307594 | D3ZUV2 |
| MIER2 | mesoderm induction early response 1, family member 2 | Human | Protein Binding | 54531 | Q8N344 |
| P4HA3 | prolyl 4-hydroxylase, alpha polypeptide III | Human | Protein Binding | 283208 | Q7Z4N8 |
| PCDH20 | Human | Protein Binding | |||
| PCDHA10 | Protocadherin alpha-10 | Human | Protein Binding | 56139 | Q9Y5I2-2 |
| PCDHA12 | Protocadherin alpha-12 | Human | Protein Binding | 56137 | Q9UN75-2 |