Human Gene Module / Chromosome 15 / FAN1

FAN1FANCD2/FANCI-associated nuclease 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 5
Rare Variants / Common Variants
6 / 0
Aliases
FAN1, KIAA1018,  KMIN,  MTMR15,  RP11-540B6.6
Associated Syndromes
-
Chromosome Band
15q13.3
Associated Disorders
SCZ
Relevance to Autism

Rare nonsynonymous variants in the FAN1 gene were found to cluster significantly in individuals affected with ASD and schizophrenia within a 20-kb window that spans several key functional domains of the gene (Ionita-Laza et al., 2013). In particular, a missense variant within the FAN1 gene that displayed a 4/0 transmitted/untransmitted ratio in schizophrenia patients was also found to have an increased frequency in ASD cases compared to controls (0.018 vs. 0.008; Barnard test one-sided P=0.039) and compared to 4600 European Americans in the NHLBI Exome Variant Server (0.018 vs. 0.0079; Barnard test one-side P=0.004).

Molecular Function

Nuclease required for maintenance of chromosomal stability. Plays a key role in DNA repair of DNA interstrand cross-links (ICL). Defects in this gene are associated with Interstitial nephritis, karyomegalic (KMIN) (MIM:614817).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to FAN1 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Scan statistic-based analysis of exome sequencing data identifies FAN1 at 15q13.3 as a susceptibility gene for schizophrenia and autism Ionita-Laza I , et al. (2013) Yes SCZ
2 Positive Association Common variants in FAN1, located in 15q13.3, confer risk for schizophrenia and bipolar disorder in Han Chinese Jian X et al. (2020) No -
3 Support - Deshmukh AL et al. (2021) No -
4 Support - Cirnigliaro M et al. (2023) Yes -
5 Support - Omri Bar et al. (2024) Yes ID
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - missense_variant Unknown - Unknown 24344280 Ionita-Laza I , et al. (2013)
c.2260C>T p.Arg754Ter stop_gained De novo - Simplex 38256266 Omri Bar et al. (2024)
c.1520G>A p.Arg507His missense_variant Unknown - Unknown 24344280 Ionita-Laza I , et al. (2013)
c.506C>G p.Ser169Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1520G>A p.Arg507His missense_variant Familial Maternal Unknown 24344280 Ionita-Laza I , et al. (2013)
c.256_257del p.Met86GlyfsTer14 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Rare nonsynonymous variants in the FAN1 gene were found to cluster significantly in individuals affected with ASD and schizophrenia within a 20-kb window that spans several key functional domains of the gene (Ionita-Laza et al., 2013). In particular, a missense variant within the FAN1 gene that displayed a 4/0 transmitted/untransmitted ratio in schizophrenia patients was also found to have an increased frequency in ASD cases compared to controls (0.018 vs. 0.008; Barnard test one-sided P=0.039) and compared to 4600 European Americans in the NHLBI Exome Variant Server (0.018 vs. 0.0079; Barnard test one-side P=0.004).

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

Rare nonsynonymous variants in the FAN1 gene were found to cluster significantly in individuals affected with ASD and schizophrenia within a 20-kb window that spans several key functional domains of the gene (Ionita-Laza et al., 2013). In particular, a missense variant within the FAN1 gene that displayed a 4/0 transmitted/untransmitted ratio in schizophrenia patients was also found to have an increased frequency in ASD cases compared to controls (0.018 vs. 0.008; Barnard test one-sided P=0.039) and compared to 4600 European Americans in the NHLBI Exome Variant Server (0.018 vs. 0.0079; Barnard test one-side P=0.004).

4/1/2020
3
icon
3

Decreased from 3 to 3

Description

Rare nonsynonymous variants in the FAN1 gene were found to cluster significantly in individuals affected with ASD and schizophrenia within a 20-kb window that spans several key functional domains of the gene (Ionita-Laza et al., 2013). In particular, a missense variant within the FAN1 gene that displayed a 4/0 transmitted/untransmitted ratio in schizophrenia patients was also found to have an increased frequency in ASD cases compared to controls (0.018 vs. 0.008; Barnard test one-sided P=0.039) and compared to 4600 European Americans in the NHLBI Exome Variant Server (0.018 vs. 0.0079; Barnard test one-side P=0.004).

Reports Added
[Common variants in FAN1, located in 15q13.3, confer risk for schizophrenia and bipolar disorder in Han Chinese2020]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Rare nonsynonymous variants in the FAN1 gene were found to cluster significantly in individuals affected with ASD and schizophrenia within a 20-kb window that spans several key functional domains of the gene (Ionita-Laza et al., 2013). In particular, a missense variant within the FAN1 gene that displayed a 4/0 transmitted/untransmitted ratio in schizophrenia patients was also found to have an increased frequency in ASD cases compared to controls (0.018 vs. 0.008; Barnard test one-sided P=0.039) and compared to 4600 European Americans in the NHLBI Exome Variant Server (0.018 vs. 0.0079; Barnard test one-side P=0.004).

Reports Added
[New Scoring Scheme]
10/1/2017
icon
4

Increased from to 4

Description

Rare nonsynonymous variants in the FAN1 gene were found to cluster significantly in individuals affected with ASD and schizophrenia within a 20-kb window that spans several key functional domains of the gene (Ionita-Laza et al., 2013). In particular, a missense variant within the FAN1 gene that displayed a 4/0 transmitted/untransmitted ratio in schizophrenia patients was also found to have an increased frequency in ASD cases compared to controls (0.018 vs. 0.008; Barnard test one-sided P=0.039) and compared to 4600 European Americans in the NHLBI Exome Variant Server (0.018 vs. 0.0079; Barnard test one-side P=0.004).

Krishnan Probability Score

Score 0.43643388316942

Ranking 20340/25841 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 1.4679258248525E-15

Ranking 17707/18225 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 0.94929387436178

Ranking 18032/18665 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 10

Ranking 185/461 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
CNVs associated with FAN1(1 CNVs)
Sort By:
15q13.3 80 Deletion-Duplication 117  /  452
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
RFC3 replication factor C (activator 1) 3, 38kDa Human Protein Binding 5983 P40938
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