Human Gene Module / Chromosome 10 / LDB1

LDB1LIM domain binding 1

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
6 / 0
EAGLE Score
4
Limited Learn More
Aliases
LDB1, CLIM-2,  CLIM2,  LDB-1,  NLI
Associated Syndromes
-
Chromosome Band
10q24.32
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation
Relevance to Autism

Two de novo protein-truncating variants in the LDB1 gene were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014; Satterstrom et al., 2020), while additional protein-truncating variants were observed in case and control samples 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 LDB1 as a candidate gene with a false discovery rate (FDR) between 0.01 and 0.05 (0.01 < FDR 0.05).

Molecular Function

Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions. Plays a role in the development of interneurons and motor neurons in cooperation with LHX3 and ISL1. Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to LDB1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Recent recommendation Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
3 Support - Wang J et al. (2023) Yes -
4 Support - Rebecca I Torene et al. (2024) No -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.361C>T p.Arg121Trp missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.938del p.Asn313ThrfsTer25 frameshift_variant De novo - - 38091987 Rebecca I Torene et al. (2024)
c.306del p.Met103CysfsTer2 frameshift_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.906del p.Gly304AlafsTer4 frameshift_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.849_852del p.Pro284LeufsTer23 frameshift_variant De novo - - 38091987 Rebecca I Torene et al. (2024)
c.798_799del p.Asp268LeufsTer58 frameshift_variant Familial Maternal - 38091987 Rebecca I Torene et al. (2024)
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
icon
1

Increased from to 1

Krishnan Probability Score

Score 0.44696130733301

Ranking 14274/25841 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 0.87945400483389

Ranking 3386/18225 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 0.41810600792468

Ranking 303/18665 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 0.26568699687281

Ranking 3250/20870 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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