Human Gene Module / Chromosome 8 / FABP4

FABP4fatty acid binding protein 4

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
4 / 0
Aliases
FABP4, A-FABP,  AFABP,  ALBP,  HEL-S-104,  aP2
Associated Syndromes
-
Chromosome Band
8q21.13
Associated Disorders
-
Relevance to Autism

Investigation of adipose tissue development as a pathophysiological marker of autism spectrum disorder by examining the serum levels of adipokines and other metabolic markers in 123 Japanese children with ASD and 92 typically developing Japanese children in Maekawa et al., 2020 found that FABP4 protein levels were significantly lower in ASD children than in typically developing subjects at preschool age (4-6 years old, 21 ASD cases and 26 typically developing controls). Furthermore, resequencing the exons of the FABP4 gene in a Japanese cohort comprising 659 ASD cases and 1000 control samples in this report led to the identification of two rare functional variants in the ASD group, including a nonsense variant transmitted to the proband from a mother with a history of depression, while disruption of the Fabp4 gene in mice evoked ASD-like behavioral phenotypes and increased spine density on apical dendrites of pyramidal neurons, which has been observed in post-mortem brains from ASD subjects. A rare de novo missense variant in the FABP4 gene had previously been identifed in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Molecular Function

FABP4 encodes the fatty acid binding protein found in adipocytes. Fatty acid binding proteins are a family of small, highly conserved, cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. It is thought that FABPs roles include fatty acid uptake, transport, and metabolism.

External Links
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Human
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SFARI Genomic Platforms
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Reports related to FABP4 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Primary A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder Maekawa M et al. (2020) Yes -
3 Support - Zhou X et al. (2022) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.217G>A p.Glu73Lys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.22A>G p.Thr8Ala missense_variant Unknown - - 33225276 Maekawa M et al. (2020)
c.239A>G p.Lys80Arg missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.294G>A p.Trp98Ter stop_gained Familial Maternal Simplex 33225276 Maekawa M et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

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.

4/1/2022
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.42318816702208

Ranking 21076/25841 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 0.004925642129412

Ranking 10592/18225 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 0.86820006333743

Ranking 4215/18665 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 -0.17848815042475

Ranking 14922/20870 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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