Human Gene Module / Chromosome 14 / LRFN5

LRFN5leucine rich repeat and fibronectin type III domain containing 5

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 7
Rare Variants / Common Variants
5 / 2
Aliases
LRFN5, C14orf146,  DKFZp686G0210,  FIGLER8,  FLJ30803,  SALM5
Associated Syndromes
-
Chromosome Band
14q21.1
Associated Disorders
ID
Relevance to Autism

Genetic association has been found between the LRFN5 gene and autism in two large cohorts (AGRE and ACC) of European ancestry and replicated in two other cohorts (CAP and CART) (Wang et al., 2009). A mutation that caused a 10-fold reduction in LRFN5 expression was found in a patient with autism (de Bruijn et al., 2010). In addition, a rare deletion in the LRFN5 gene has been identified with developmental delay and intellectual disability (Mikhail et al., 2011).

Molecular Function

Cell adhesion molecule that mediates homophilic cell-cell adhesion in a Ca2+-independent manner. Promotes neurite outgrowth in hippocampal neurons.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to LRFN5 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Common genetic variants on 5p14.1 associate with autism spectrum disorders Wang K , et al. (2009) Yes -
2 Support Severe Progressive Autism Associated with Two de novo Changes: A 2.6-Mb 2q31.1 Deletion and a Balanced t(14;21)(q21.1;p11.2) Translocation with Long-Range Epigenetic Silencing of LRFN5 Expression de Bruijn DR , et al. (2010) Yes -
3 Recent Recommendation Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental retardation, and/or autism spectrum disorders Mikhail FM , et al. (2011) No ID
4 Positive Association A genome-wide association study of autism incorporating autism diagnostic interview-revised, autism diagnostic observation schedule, and social responsiveness scale Connolly JJ , et al. (2012) Yes -
5 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
6 Support Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnosed diseases Farwell Hagman KD , et al. (2016) No -
7 Recent Recommendation - Lybaek H et al. (2022) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss - - - 22031302 Mikhail FM , et al. (2011)
- - translocation De novo - - 20648246 de Bruijn DR , et al. (2010)
c.758G>A p.Arg253His missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.575C>T p.Ser192Phe missense_variant Unknown - - 27513193 Farwell Hagman KD , et al. (2016)
c.869C>T p.Thr290Ile missense_variant Unknown - - 27513193 Farwell Hagman KD , et al. (2016)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - intergenic_variant - - - 22935194 Connolly JJ , et al. (2012)
- G to A intergenic_variant - - - 19404256 Wang K , et al. (2009)
SFARI Gene score
2

Strong Candidate

LRFN5 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). LRFN5 shows altered expression in this individual; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

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

LRFN5 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). LRFN5 shows altered expression in this individual; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

LRFN5 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). LRFN5 shows altered expression in this individual; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

Reports Added
[New Scoring Scheme]
7/1/2016
4
icon
4

Decreased from 4 to 4

Description

LRFN5 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). LRFN5 shows altered expression in this individual; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

Reports Added
[Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnose...2016]
1/1/2016
4
icon
4

Decreased from 4 to 4

Description

LRFN5 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). LRFN5 shows altered expression in this individual; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

Reports Added
[Common genetic variants on 5p14.1 associate with autism spectrum disorders.2009] [Severe Progressive Autism Associated with Two de novo Changes: A 2.6-Mb 2q31.1 Deletion and a Balanced t(14;21)(q21.1;p11.2) Translocation with Lon...2010] [A genome-wide association study of autism incorporating autism diagnostic interview-revised, autism diagnostic observation schedule, and social res...2012] [Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental...2011] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

LRFN5 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). LRFN5 shows altered expression in this individual; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

LRFN5 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). LRFN5 shows altered expression in this individual; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

Krishnan Probability Score

Score 0.50617068619447

Ranking 1887/25841 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 0.71232478324146

Ranking 4414/18225 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 0.73966179811213

Ranking 1457/18665 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 13.5

Ranking 144/461 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
Zhang D Score

Score 0.13692337273888

Ranking 5417/20870 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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