Human Gene Module / Chromosome 12 / FBRSL1

FBRSL1fibrosin like 1

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
2 / 6
Rare Variants / Common Variants
7 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
12q24.33
Associated Disorders
ASD
Relevance to Autism

Ufartes et al., 2020 reported three individuals with truncating variants in the FBRSL1 gene presenting with a syndrome characterized by global developmental delay/intellectual disability, speech delay, autistic behavior, microcephaly, swallowing difficulties, postnatal growth retardation, skeletal abnormalities, respiratory failure, and dysmorphic features; Kastens et al., 2025 subsequently found that truncating FBRSL1 variants led to downregulation of BRPF1 and KAT6A in blood and fibroblasts derived from these patients. Additional individuals with truncating FBRSL1 variants presenting with similar phenotypes were reported in Bukvic et al., 2024 and Xu et al., 2025; Xu et al., 2025 also found that fbrsl1 zebrafish knockdown models recapitulated neurodevelopmental abnormalities, epileptiform discharges, and cardiac dysfunction.

Molecular Function

FBRSL1 is a paralog of AUTS2. Using chromatin immunoprecipitation followed by sequencing (ChIP-Seq), Kastens et al., 2025 demonstrated that FBRSL1 regulates the expression of the chromatin regulators BRPF1 and KAT6A, two epigenetic regulators involved in embryonic development and linked to neurodevelopmental disorders.

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Reports related to FBRSL1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo mutations in FBRSL1 cause a novel recognizable malformation and intellectual disability syndrome Ufartes R et al. (2020) No Autistic behavior
2 Support - Zhou X et al. (2022) Yes -
3 Support - Cirnigliaro M et al. (2023) Yes -
4 Support - Nenad Bukvic et al. (2024) No Autistic behavior, stereotypy
5 Support - Gina Kastens et al. (2025) No Autistic behavior
6 Support - Dan Xu et al. (2026) No Autistic behavior
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.487C>T p.Gln163Ter stop_gained De novo - - 32424618 Ufartes R et al. (2020)
c.1670G>A p.Arg557Gln missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.332G>A p.Trp111Ter stop_gained Unknown Not maternal - 32424618 Ufartes R et al. (2020)
c.380dup p.Ala128CysfsTer5 frameshift_variant De novo - Simplex 41232796 Dan Xu et al. (2026)
c.581_603del p.Ser194LysfsTer6 frameshift_variant De novo - - 32424618 Ufartes R et al. (2020)
c.371dupC p.Cys125LeufsTer7 frameshift_variant De novo - Simplex 39062605 Nenad Bukvic et al. (2024)
c.1681dup p.Ala561GlyfsTer3 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
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."

Krishnan Probability Score

Score 0.44765821412136

Ranking 12088/25841 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
Sanders TADA Score

Score 0.94174642248295

Ranking 15047/18665 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 -0.058738784389628

Ranking 10743/20870 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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