Human Gene Module / Chromosome 7 / ICA1

ICA1islet cell autoantigen 1

Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
7 / 8
Rare Variants / Common Variants
8 / 0
ICA1, ICA69,  ICAp69
Associated Syndromes
Genetic Category
Rare Single Gene Mutation
Chromosome Band
Associated Disorders
Relevance to Autism

A rare duplication in the ICA1 gene has been identified with ASD (Salyakina et al., 2011).

Molecular Function

This gene encodes a protein with an arfaptin homology domain that is found both in the cytosol and as membrane-bound form on the Golgi complex and immature secretory granules. This protein is believed to be an autoantigen in insulin-dependent diabetes mellitus and primary Sjogren's syndrome.

Reports related to ICA1 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Microduplications in an autism multiplex family narrow the region of susceptibility for developmental disorders on 15q24 and implicate 7p21. Cukier HN , et al. (2011) Yes -
2 Primary Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk. Salyakina D , et al. (2011) Yes ID
3 Support De novo gene disruptions in children on the autistic spectrum. Iossifov I , et al. (2012) Yes -
4 Support Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder. Girirajan S , et al. (2013) Yes -
5 Support Prospective diagnostic analysis of copy number variants using SNP microarrays in individuals with autism spectrum disorders. Nava C , et al. (2013) Yes ID
6 Recent Recommendation An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders. Chen S , et al. (2018) No -
7 Recent Recommendation Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights. Kushima I , et al. (2018) Yes -
8 Support Both rare and common genetic variants contribute to autism in the Faroe Islands. Leblond CS , et al. (2019) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Unknown - - 30208311 Kushima I , et al. (2018)
- - copy_number_loss Unknown - - 30208311 Kushima I , et al. (2018)
- - copy_number_gain Familial Maternal Simplex 23632794 Nava C , et al. (2013)
- - copy_number_gain Familial Paternal Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_gain Familial Paternal Multiplex 23375656 Girirajan S , et al. (2013)
c.1328A>G p.Gln443Arg missense_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
- - copy_number_gain Familial Maternal Extended multiplex 22016809 Salyakina D , et al. (2011)
delA p.Val49Ter frameshift_variant Familial Paternal Simplex 30675382 Leblond CS , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score

Suggestive Evidence


Score Delta: Score remained at 4.1


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.

No data

Increased from No data to 4


Rare duplications of 7p21 that include the ICA1 gene have been identified with ASD (Salyakina et al., 2011; Cukier et al., 2011).

No data

Increased from No data to 4


Rare duplications of 7p21 that include the ICA1 gene have been identified with ASD (Salyakina et al., 2011; Cukier et al., 2011).

Krishnan Probability Score

Score 0.56678514992753

Ranking 1203/25841 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 0.0049503682925165

Ranking 10590/18225 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 0.74952751905136

Ranking 1550/18665 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
Larsen Cumulative Evidence Score

Score 4

Ranking 311/461 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 0.34202555317624

Ranking 2116/20870 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 ICA1(1 CNVs)
7p21.3 27 Deletion-Duplication 48  /  312
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
STK16 serine/threonine kinase 16 Human Protein Binding 8576 O75716
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