Human Gene Module / Chromosome 19 / LIN7B

LIN7Blin-7 homolog B, crumbs cell polarity complex component

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
3 / 0
Aliases
LIN7B, UNQ3116/PRO10200,  LIN-7B,  MALS-2,  MALS2,  VELI2
Associated Syndromes
-
Chromosome Band
19q13.33
Associated Disorders
-
Relevance to Autism

Two variants affecting LIN7B (a de novo multigenic duplication and a novel frameshift variant) were identified in unrelated ASD patients. Acute knockdown of Lin-7B in mice brains led to abnormal neuronal migration during corticogenesis, and while wild-type hLin-7B was able to rescue this phenotype, hLin-7B with the aforementioned ASD-associated frameshift variant failed to do so (Mizuno et al., 2014).

Molecular Function

Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to LIN7B (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Role of an adaptor protein Lin-7B in brain development: possible involvement in autism spectrum disorders Mizuno M , et al. (2014) Yes -
2 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
3 Support - Zhou X et al. (2022) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain De novo - - 25196215 Mizuno M , et al. (2014)
c.1A>C p.Met1? initiator_codon_variant De novo - - 35982159 Zhou X et al. (2022)
c.392+1G>C - splice_site_variant Unknown - Unknown 25196215 Mizuno M , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two variants affecting LIN7B (a de novo multigenic duplication and a novel frameshift variant) were identified in unrelated ASD patients. Acute knockdown of Lin-7B in mice brains led to abnormal neuronal migration during corticogenesis, and while wild-type hLin-7B was able to rescue this phenotype, hLin-7B with the aforementioned ASD-associated frameshift variant failed to do so (Mizuno et al., 2014).

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

Two variants affecting LIN7B (a de novo multigenic duplication and a novel frameshift variant) were identified in unrelated ASD patients. Acute knockdown of Lin-7B in mice brains led to abnormal neuronal migration during corticogenesis, and while wild-type hLin-7B was able to rescue this phenotype, hLin-7B with the aforementioned ASD-associated frameshift variant failed to do so (Mizuno et al., 2014).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two variants affecting LIN7B (a de novo multigenic duplication and a novel frameshift variant) were identified in unrelated ASD patients. Acute knockdown of Lin-7B in mice brains led to abnormal neuronal migration during corticogenesis, and while wild-type hLin-7B was able to rescue this phenotype, hLin-7B with the aforementioned ASD-associated frameshift variant failed to do so (Mizuno et al., 2014).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

Two variants affecting LIN7B (a de novo multigenic duplication and a novel frameshift variant) were identified in unrelated ASD patients. Acute knockdown of Lin-7B in mice brains led to abnormal neuronal migration during corticogenesis, and while wild-type hLin-7B was able to rescue this phenotype, hLin-7B with the aforementioned ASD-associated frameshift variant failed to do so (Mizuno et al., 2014).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2018
icon
4

Increased from to 4

Description

Two variants affecting LIN7B (a de novo multigenic duplication and a novel frameshift variant) were identified in unrelated ASD patients. Acute knockdown of Lin-7B in mice brains led to abnormal neuronal migration during corticogenesis, and while wild-type hLin-7B was able to rescue this phenotype, hLin-7B with the aforementioned ASD-associated frameshift variant failed to do so (Mizuno et al., 2014).

Krishnan Probability Score

Score 0.47000510098376

Ranking 8928/25841 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 0.83883724962791

Ranking 3697/18225 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 0.92109201594558

Ranking 9309/18665 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 6

Ranking 259/461 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 0.12304204614448

Ranking 5669/20870 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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