Human Gene Module / Chromosome 7 / LAMB1

LAMB1laminin, beta 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
11 / 11
Rare Variants / Common Variants
19 / 2
Aliases
LAMB1, CLM
Associated Syndromes
-
Chromosome Band
7q31.1
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the LAMB1 gene and autism. Positive association with a LAMB1 SNP was found in the Collaborative Linkage Study of Autism cohort (Hutcheson et al., 2004).

Molecular Function

The encoded protein belongs to the family of extracellular matrix glycoproteins. It is a subunit of laminin 1, laminin 2 and laminin 6.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to LAMB1 (11 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes Hutcheson HB , et al. (2004) Yes -
2 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
3 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
4 Positive Association LAMB1 polymorphism is associated with autism symptom severity in Korean autism spectrum disorder patients Kim YJ , et al. (2015) Yes -
5 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
6 Support Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes Guo H , et al. (2018) Yes -
7 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Yuan B et al. (2023) Yes -
10 Support - Wang J et al. (2023) Yes -
11 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (19)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3295-4G>A - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
c.2647T>C p.Cys883Arg missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.4930G>A p.Ala1644Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.5324T>C p.Ile1775Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.4931C>T p.Ala1644Val missense_variant De novo - - 36881370 Yuan B et al. (2023)
c.459G>A p.Ser153%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.-8del - frameshift_variant Familial Paternal Simplex 30504930 Guo H , et al. (2018)
c.4720C>T p.Arg1574Ter stop_gained De novo - Simplex 29346770 Takata A , et al. (2018)
c.1505A>G p.Asn502Ser missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.5189T>C p.Leu1730Ser missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.4931C>T p.Ala1644Val missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.1637G>C p.Gly546Ala missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.116C>A p.Thr39Lys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.5035G>A p.Val1679Met missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.3388C>T p.Arg1130Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.5065-3_5065-2dup - splice_site_variant Familial Paternal Simplex 31398340 Ruzzo EK , et al. (2019)
c.1293del p.Asn431LysfsTer17 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.4408_4409del p.Leu1470GlufsTer4 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.3490_3499del p.Lys1164GlufsTer22 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.213+387G>A - intron_variant - - - 15128462 Hutcheson HB , et al. (2004)
c.3392-36T>C;c.3650-36T>C - intron_variant - - - 25774865 Kim YJ , et al. (2015)
SFARI Gene score
2

Strong Candidate

Nominally significant association within a genome-wide significant linkage region in two separate studies, missense variants observed in cases (n=48) but not controls (>300), likewise nominal (Hutcheson HB et al.). Additional studies show upregulation in hippocampus and serum in epilepsy vs. control (Wu Y, 2008).

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Nominally significant association within a genome-wide significant linkage region in two separate studies, missense variants observed in cases (n=48) but not controls (>300), likewise nominal (Hutcheson HB et al.). Additional studies show upregulation in hippocampus and serum in epilepsy vs. control (Wu Y, 2008).

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

Nominally significant association within a genome-wide significant linkage region in two separate studies, missense variants observed in cases (n=48) but not controls (>300), likewise nominal (Hutcheson HB et al.). Additional studies show upregulation in hippocampus and serum in epilepsy vs. control (Wu Y, 2008).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2018
3
icon
3

Decreased from 3 to 3

Description

Nominally significant association within a genome-wide significant linkage region in two separate studies, missense variants observed in cases (n=48) but not controls (>300), likewise nominal (Hutcheson HB et al.). Additional studies show upregulation in hippocampus and serum in epilepsy vs. control (Wu Y, 2008).

Reports Added
[Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes.2018]
1/1/2016
3
icon
3

Decreased from 3 to 3

Description

Nominally significant association within a genome-wide significant linkage region in two separate studies, missense variants observed in cases (n=48) but not controls (>300), likewise nominal (Hutcheson HB et al.). Additional studies show upregulation in hippocampus and serum in epilepsy vs. control (Wu Y, 2008).

Reports Added
[Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes.2004] [LAMB1 polymorphism is associated with autism symptom severity in Korean autism spectrum disorder patients.2015] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014]
4/1/2015
3
icon
3

Decreased from 3 to 3

Description

Nominally significant association within a genome-wide significant linkage region in two separate studies, missense variants observed in cases (n=48) but not controls (>300), likewise nominal (Hutcheson HB et al.). Additional studies show upregulation in hippocampus and serum in epilepsy vs. control (Wu Y, 2008).

Reports Added
[LAMB1 polymorphism is associated with autism symptom severity in Korean autism spectrum disorder patients.2015]
7/1/2014
No data
icon
3

Increased from No data to 3

Description

Nominally significant association within a genome-wide significant linkage region in two separate studies, missense variants observed in cases (n=48) but not controls (>300), likewise nominal (Hutcheson HB et al.). Additional studies show upregulation in hippocampus and serum in epilepsy vs. control (Wu Y, 2008).

4/1/2014
No data
icon
3

Increased from No data to 3

Description

Nominally significant association within a genome-wide significant linkage region in two separate studies, missense variants observed in cases (n=48) but not controls (>300), likewise nominal (Hutcheson HB et al.). Additional studies show upregulation in hippocampus and serum in epilepsy vs. control (Wu Y, 2008).

Krishnan Probability Score

Score 0.3319739303068

Ranking 24673/25841 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 1.794400282223E-6

Ranking 14845/18225 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 0.4152325780768

Ranking 299/18665 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 1

Ranking 425/461 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 0.4510885888969

Ranking 911/20870 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
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ACHE acetylcholinesterase Mouse Protein Binding 11423 P21836
DEFA1 Neutrophil defensin 1 Human Protein Binding 1667 P59665
LYZL2 Lysozyme-like protein 2 Human Protein Binding 119180 Q7Z4W2-2
OS9 Protein OS-9 Human Protein Binding 10956 Q13438
SERPINA12 Serpin A12 Human Protein Binding 145264 Q8IW75
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