Human Gene Module / Chromosome 17 / RAB11FIP4

RAB11FIP4RAB11 family interacting protein 4

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 3
Rare Variants / Common Variants
3 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
17q11.2
Associated Disorders
-
Relevance to Autism

Trio-exome sequencing of 745 participants with NDD and/or epilepsy from the Center for Medical Genetics of the University Hospital Antwerp in Smal et al., 2024 identified a de novo missense variant in the RAB11FIP4 gene (NM_032932.6:c.1274G>A;p.Arg425Lys) in a patient presenting with autism spectrum disorder and global developmental delay. De novo frameshift variants in this gene had previously been reported in two male ASD probands from the SPARK cohort in Zhou et al., 2022. An intronic variant in RAB11FIP4 (SNP ID rs178850) was found to be associated with growth and neurological development phenotypes (lambda and Adaptive Bailey, respectively; P-value 2.02E-08) In a population of healthy infants studied in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) program in Uechi et al., 2020.

Molecular Function

The protein encoded by this gene interacts with RAB11 and is thought to be involved in bringing recycling endosome membranes to the cleavage furrow in late cytokinesis. Hypoxic conditions can lead to an upregulation of the encoded protein and enhance the metastatic potential of hepatocellular carcinoma.

External Links
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Human
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SFARI Genomic Platforms
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Reports related to RAB11FIP4 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Positive Association - Lisa Uechi et al. (2020) No -
2 Support - Zhou X et al. (2022) Yes -
3 Primary - Noor Smal et al. () Yes DD
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1274G>A p.Arg425Lys missense_variant De novo - Simplex 38965372 Noor Smal et al. ()
c.1480del p.Glu494ArgfsTer37 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.1275_1276insAGAAACTG p.Val426ArgfsTer18 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2024
3

Initial score established: 3

Krishnan Probability Score

Score 0.49448109267131

Ranking 3631/25841 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 0.99366361330939

Ranking 1623/18225 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 0.93633580973226

Ranking 13163/18665 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
Zhang D Score

Score 0.083568286903939

Ranking 6464/20870 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
CNVs associated with RAB11FIP4(1 CNVs)
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17q11.2 29 Deletion-Duplication 44  /  116
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