Human Gene Module / Chromosome 2 / RAB11FIP5

RAB11FIP5RAB11 family interacting protein 5

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
5 / 0
Aliases
RAB11FIP5, DKFZp434H018,  GAF1,  KIAA0857,  RIP11,  pp75
Associated Syndromes
-
Chromosome Band
2p13.2
Associated Disorders
-
Relevance to Autism

A de novo translocation identified in a male patient with PDD-NOS was demonstrated to directly interrupt the RAB11FIP5 gene in Roohi et al., 2008. Missense variants in this gene have also been identified in individuals with ASD in two studies (Matsunami et al., 2014; Yuen et al., 2016). Knockout of Rab11fip5 was shown to abolish hippocampal long-term depression in acute slices and cultured neurons, while Rab11Fip5 knockout mice were shown to display enhanced contextual fear extinction, in Bacaj et al., 2015.

Molecular Function

Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. Involved in insulin granule exocytosis. May regulate V-ATPase intracellular transport in response to extracellular acidosis.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to RAB11FIP5 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary A de novo apparently balanced translocation [46,XY,t(2;9)(p13;p24)] interrupting RAB11FIP5 identifies a potential candidate gene for autism spectrum disorder Roohi J , et al. (2008) Yes -
2 Recent Recommendation Identification of rare DNA sequence variants in high-risk autism families and their prevalence in a large case/control population Matsunami N , et al. (2014) Yes -
3 Recent Recommendation Synaptic Function of Rab11Fip5: Selective Requirement for Hippocampal Long-Term Depression Bacaj T , et al. (2015) No -
4 Support Genome-wide characteristics of de novo mutations in autism Yuen RK et al. (2016) Yes -
5 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
6 Support - Yoon J et al. (2021) No -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation De novo - Simplex 18384058 Roohi J , et al. (2008)
c.343C>T p.Arg115Cys missense_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
c.1955C>A p.Pro652His missense_variant Unknown - Unknown 24467814 Matsunami N , et al. (2014)
c.181G>T p.Glu61Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1955C>T p.Pro652Leu missense_variant Familial Maternal Multiplex 24467814 Matsunami N , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo translocation identified in a male patient with PDD-NOS was demonstrated to directly interrupt the RAB11FIP5 gene in Roohi et al., 2008. Missense variants in this gene have also been identified in individuals with ASD in two studies (Matsunami et al., 2014; Yuen et al., 2016). Knockout of Rab11fip5 was shown to abolish hippocampal long-term depression in acute slices and cultured neurons, while Rab11Fip5 knockout mice were shown to display enhanced contextual fear extinction, in Bacaj et al., 2015.

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A de novo translocation identified in a male patient with PDD-NOS was demonstrated to directly interrupt the RAB11FIP5 gene in Roohi et al., 2008. Missense variants in this gene have also been identified in individuals with ASD in two studies (Matsunami et al., 2014; Yuen et al., 2016). Knockout of Rab11fip5 was shown to abolish hippocampal long-term depression in acute slices and cultured neurons, while Rab11Fip5 knockout mice were shown to display enhanced contextual fear extinction, in Bacaj et al., 2015.

1/1/2021
3
icon
3

Decreased from 3 to 3

Description

A de novo translocation identified in a male patient with PDD-NOS was demonstrated to directly interrupt the RAB11FIP5 gene in Roohi et al., 2008. Missense variants in this gene have also been identified in individuals with ASD in two studies (Matsunami et al., 2014; Yuen et al., 2016). Knockout of Rab11fip5 was shown to abolish hippocampal long-term depression in acute slices and cultured neurons, while Rab11Fip5 knockout mice were shown to display enhanced contextual fear extinction, in Bacaj et al., 2015.

Reports Added
[Rab11fip5 regulates telencephalon development via ephrinB1 recycling2021]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo translocation identified in a male patient with PDD-NOS was demonstrated to directly interrupt the RAB11FIP5 gene in Roohi et al., 2008. Missense variants in this gene have also been identified in individuals with ASD in two studies (Matsunami et al., 2014; Yuen et al., 2016). Knockout of Rab11fip5 was shown to abolish hippocampal long-term depression in acute slices and cultured neurons, while Rab11Fip5 knockout mice were shown to display enhanced contextual fear extinction, in Bacaj et al., 2015.

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

A de novo translocation identified in a male patient with PDD-NOS was demonstrated to directly interrupt the RAB11FIP5 gene in Roohi et al., 2008. Missense variants in this gene have also been identified in individuals with ASD in two studies (Matsunami et al., 2014; Yuen et al., 2016). Knockout of Rab11fip5 was shown to abolish hippocampal long-term depression in acute slices and cultured neurons, while Rab11Fip5 knockout mice were shown to display enhanced contextual fear extinction, in Bacaj et al., 2015.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2018
icon
4

Increased from to 4

Description

A de novo translocation identified in a male patient with PDD-NOS was demonstrated to directly interrupt the RAB11FIP5 gene in Roohi et al., 2008. Missense variants in this gene have also been identified in individuals with ASD in two studies (Matsunami et al., 2014; Yuen et al., 2016). Knockout of Rab11fip5 was shown to abolish hippocampal long-term depression in acute slices and cultured neurons, while Rab11Fip5 knockout mice were shown to display enhanced contextual fear extinction, in Bacaj et al., 2015.

Krishnan Probability Score

Score 0.4931385565788

Ranking 4277/25841 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 0.0026759163117969

Ranking 11075/18225 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 0.93809196376846

Ranking 13745/18665 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 12

Ranking 162/461 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 0.1642505924288

Ranking 4906/20870 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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