Human Gene Module / Chromosome X / FGF13

FGF13fibroblast growth factor 13

SFARI Gene Score
3S
Suggestive Evidence, Syndromic Criteria 3.1, Syndromic
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
7 / 0
Aliases
FGF13, DEE90,  FGF-13,  FGF2,  FHF-2,  FHF2,  LINC00889
Associated Syndromes
-
Chromosome Band
Xq26.3
Associated Disorders
ASD
Relevance to Autism

Fry et al., 2021 demonstrated that missense variants in the N-terminal domain of the A isoform of the FGF13 gene caused an X-linked developmental and epileptic encephalopathy (developmental and epileptic encephalopathy-90; OMIM 301058); all seven affected individuals in this report (two sibling pairs and three unrelated males) presented with intractable focal seizures and severe-profound developmental delay/intellectual disability, and four individuals were diagnosed with autism spectrum disorder. Furthermore, functional characterization of FGF13 missense variants in this report revealed that mutation proteins lost the ability to induce rapid-onset, long-term blockade of wild-type Nav1.6 (SCN8A) channels while retaining pro-excitatory properties, consistent with a gain-of-function effect. Application of sdMAF separately to ASD individual and control cohorts in an X-chromosome-wide association study of 6,873 individuals with autism from MSSNG, SSC, and SPARK (5,639 males and 1,234 females) and 8,981 controls (3,911 males and 5,070 females) in Mendes et al., 2025 identified a statistically significant region including the FGF13 gene in which all SNPs exhibited higher MAFs in males than females [the lead SNP for this region (rs555083289) had a sdMAF P-value of 1.19E-05].

Molecular Function

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked cognitive disability mapping to this region.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
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SFARI Genomic Platforms
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Reports related to FGF13 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary - Fry AE et al. (2021) No ASD
2 Support - Bruno LP et al. (2021) Yes -
3 Support - Afif Ben-Mahmoud et al. (2024) Yes DD, ID
4 Positive association - Marla Mendes et al. (2025) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.50-2045C>T - missense_variant Unknown - Multiplex 33245860 Fry AE et al. (2021)
c.31C>T p.Arg11Cys missense_variant De novo - Simplex 33245860 Fry AE et al. (2021)
c.32G>C p.Arg11Pro missense_variant De novo - Simplex 33245860 Fry AE et al. (2021)
c.41G>C p.Arg14Thr missense_variant Unknown - Multiplex 33245860 Fry AE et al. (2021)
c.31C>T p.Arg11Cys missense_variant Familial Maternal Multiplex 33245860 Fry AE et al. (2021)
c.80_82del p.Cys27_Val28delinsPhe inframe_deletion De novo - Simplex 34948243 Bruno LP et al. (2021)
c.545G>T p.Gly182Val missense_variant Familial Maternal Simplex 39519104 Afif Ben-Mahmoud et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
3S

Suggestive Evidence, Syndromic

Score Delta: Score remained at 3S

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.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2022
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3S

Increased from to 3S

Krishnan Probability Score

Score 0.57766978433882

Ranking 626/25841 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 0.96422363977239

Ranking 2461/18225 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 0.93904041995212

Ranking 14071/18665 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 0.28487321113022

Ranking 2950/20870 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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