Human Gene Module / Chromosome 11 / LRRC4C

LRRC4Cleucine rich repeat containing 4C

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
4 / 0
EAGLE Score
1.25
Limited Learn More
Aliases
LRRC4C, NGL-1,  NGL1
Associated Syndromes
-
Chromosome Band
11p12
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation
Relevance to Autism

Three de novo missense variants, including one that was predicted to be probably damaging (defined as MPC 2), were identified in the LRRC4C gene in ASD probands from the Autism Sequencing Consortium, while a protein-truncating variant in this gene was observed in a case sample from the Danish iPSYCH study (Satterstrom et al., 2020). TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in Satterstrom et al., 2020 identified LRRC4C as a candidate gene with a false discovery rate (FDR) between 0.05 and 0.1 (0.05 < FDR 0.1).

Molecular Function

NGL1 is a specific binding partner for netrin G1 (NTNG1), which is a member of the netrin family of axon guidance molecules, and it may promote neurite outgrowth of developing thalamic neurons.

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Reports related to LRRC4C (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
2 Support - Mahjani B et al. (2021) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.488T>A p.Ile163Asn missense_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.467G>A p.Arg156Gln missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.488T>A p.Ile163Asn missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1792T>C p.Tyr598His missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 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
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1

Increased from to 1

Krishnan Probability Score

Score 0.55431766252957

Ranking 1354/25841 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 0.95373086870595

Ranking 2618/18225 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 0.95005847069953

Ranking 18341/18665 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 0.20328199657106

Ranking 4209/20870 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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