Human Gene Module / Chromosome 11 / APBB1

APBB1amyloid beta precursor protein binding family B member 1

Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
3 / 0
APBB1, FE65,  MGC:9072,  RIR
Associated Syndromes
Genetic Category
Rare Single Gene Mutation, Functional
Chromosome Band
Associated Disorders
Relevance to Autism

A de novo loss-of-function variant in the APBB1 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. TADA-Annotations (TADA-A) analysis of whole-genome sequencing data from five studies with a total of 314 ASD-affected subjects in Liu et al., 2018 identified APBB1 as an ASD risk gene with a false discovery rate (FDR) < 0.1; among the de novo variants associated with this gene in ASD subjects was a loss-of-function variant, a regulatory SNV, and two conserved regulatory SNVs. APBB1 expression had previously been shown to be significantly down-regulated in the cerebellum of autistic patients (Zeidn-Chuli et al., 2014).

Molecular Function

Transcription coregulator that can have both coactivator and corepressor functions. Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain.

Reports related to APBB1 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Altered expression of Alzheimer's disease-related genes in the cerebellum of autistic patients: a model for disrupted brain connectome and therapy. Zeidn-Chuli F , et al. (2014) Yes -
2 Primary The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
3 Recent Recommendation A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies. Liu Y , et al. (2018) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - loss_of_function_variant De novo - - 29754769 Liu Y , et al. (2018)
- - regulatory_region_variant De novo - - 29754769 Liu Y , et al. (2018)
insC - frameshift_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score

Suggestive Evidence



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.


Initial score established: 3.3



Krishnan Probability Score

Score 0.49710990505783

Ranking 2444/25841 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: A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at
ExAC Score

Score 0.98699365222094

Ranking 1929/18225 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 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: aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.48742716493548

Ranking 422/18665 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
Zhang D Score

Score 0.36195872581836

Ranking 1878/20870 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.
CNVs associated with APBB1(1 CNVs)
11p15.4 33 Deletion-Duplication 53  /  269
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