Human Gene Module / Chromosome 9 / LMX1B

LMX1BLIM homeobox transcription factor 1 beta

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
3 / 2
Aliases
LMX1B, LMX1.2,  MGC138325,  MGC142051,  NPS1
Associated Syndromes
-
Chromosome Band
9q33.3
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011), with two SNPs (rs10732392 and rs12336217) showing moderate association with autism with p values of 0.018 and 0.022, respectively, in a transmission disequilibrium test. LMX1B transcripts were found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p=0.049) in this report.

Molecular Function

This gene encodes a member of the LIM-homeodomain family of proteins containing two N-terminal zinc-binding LIM domains, 1 homeodomain, and a C-terminal glutamine-rich domain. It functions as a transcription factor, and is essential for the normal development of dorsal limb structures, the glomerular basement membrane, the anterior segment of the eye, and dopaminergic and serotonergic neurons.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to LMX1B (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Association of transcription factor gene LMX1B with autism Thanseem I , et al. (2011) Yes -
2 Support - Trost B et al. (2022) Yes -
3 Support - Axel Schmidt et al. (2024) No -
4 Support - Suhua Chang et al. () Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.453C>T p.Arg151= synonymous_variant De novo - - 36368308 Trost B et al. (2022)
c.1052-2A>C - splice_site_variant De novo - Simplex 39126614 Suhua Chang et al. ()
c.706G>C p.Ala236Pro missense_variant Unknown - - 39039281 Axel Schmidt et al. (2024)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.326+18189A>G - intron_variant - - - 21901133 Thanseem I , et al. (2011)
c.326+22022A>G - intron_variant - - - 21901133 Thanseem I , et al. (2011)
SFARI Gene score
2

Strong Candidate

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011), with two SNPs (rs10732392 and rs12336217) showing moderate association with autism with p values of 0.018 and 0.022, respectively, in a transmission disequilibrium test. LMX1B transcripts were found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p=0.049) in this report.

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

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011), with two SNPs (rs10732392 and rs12336217) showing moderate association with autism with p values of 0.018 and 0.022, respectively, in a transmission disequilibrium test. LMX1B transcripts were found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p=0.049) in this report.

Reports Added
[New Scoring Scheme]
1/1/2019
4
icon
3

Decreased from 4 to 3

Description

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011), with two SNPs (rs10732392 and rs12336217) showing moderate association with autism with p values of 0.018 and 0.022, respectively, in a transmission disequilibrium test. LMX1B transcripts were found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p=0.049) in this report.

10/1/2018
3
icon
4

Increased from 3 to 4

Description

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011), with two SNPs (rs10732392 and rs12336217) showing moderate association with autism with p values of 0.018 and 0.022, respectively, in a transmission disequilibrium test. LMX1B transcripts were found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p=0.049) in this report.

10/1/2018
4
icon
3

Decreased from 4 to 3

Description

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011). In that study, the authors showed nominally significant association of 2 markers in LMX1B and a significant decrease in LMX1B expression in the anterior cingulate gyrus of individuals with ASD compared to controls.

7/1/2018
3
icon
4

Increased from 3 to 4

Description

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011), with two SNPs (rs10732392 and rs12336217) showing moderate association with autism with p values of 0.018 and 0.022, respectively, in a transmission disequilibrium test. LMX1B transcripts were found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p=0.049) in this report.

4/1/2017
4
icon
3

Decreased from 4 to 3

Description

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011). In that study, the authors showed nominally significant association of 2 markers in LMX1B and a significant decrease in LMX1B expression in the anterior cingulate gyrus of individuals with ASD compared to controls.

1/1/2017
3
icon
4

Increased from 3 to 4

Description

Genetic association was found between two intronic SNPs in the LMX1B gene and autism in a Caucasian AGRE cohort (PMID 21901133).

10/1/2016
3
icon
4

Increased from 3 to 4

Description

Genetic association was found between two intronic SNPs in the LMX1B gene and autism in a Caucasian AGRE cohort (PMID 21901133).

10/1/2016
4
icon
3

Decreased from 4 to 3

Description

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011). In that study, the authors showed nominally significant association of 2 markers in LMX1B and a significant decrease in LMX1B expression in the anterior cingulate gyrus of individuals with ASD compared to controls.

7/1/2016
4
icon
3

Decreased from 4 to 3

Description

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011). In that study, the authors showed nominally significant association of 2 markers in LMX1B and a significant decrease in LMX1B expression in the anterior cingulate gyrus of individuals with ASD compared to controls.

7/1/2016
3
icon
4

Increased from 3 to 4

Description

Genetic association was found between two intronic SNPs in the LMX1B gene and autism in a Caucasian AGRE cohort (PMID 21901133).

4/1/2016
4
icon
3

Decreased from 4 to 3

Description

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011). In that study, the authors showed nominally significant association of 2 markers in LMX1B and a significant decrease in LMX1B expression in the anterior cingulate gyrus of individuals with ASD compared to controls.

4/1/2016
3
icon
4

Increased from 3 to 4

Description

Genetic association was found between two intronic SNPs in the LMX1B gene and autism in a Caucasian AGRE cohort (PMID 21901133).

1/1/2016
3
icon
4

Increased from 3 to 4

Description

Genetic association was found between two intronic SNPs in the LMX1B gene and autism in a Caucasian AGRE cohort (PMID 21901133).

1/1/2016
4
icon
3

Decreased from 4 to 3

Description

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011). In that study, the authors showed nominally significant association of 2 markers in LMX1B and a significant decrease in LMX1B expression in the anterior cingulate gyrus of individuals with ASD compared to controls.

10/1/2015
4
icon
3

Decreased from 4 to 3

Description

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011). In that study, the authors showed nominally significant association of 2 markers in LMX1B and a significant decrease in LMX1B expression in the anterior cingulate gyrus of individuals with ASD compared to controls.

10/1/2015
3
icon
4

Increased from 3 to 4

Description

Genetic association was found between two intronic SNPs in the LMX1B gene and autism in a Caucasian AGRE cohort (PMID 21901133).

7/1/2015
3
icon
4

Increased from 3 to 4

Description

Genetic association was found between two intronic SNPs in the LMX1B gene and autism in a Caucasian AGRE cohort (PMID 21901133).

7/1/2014
No data
icon
3

Increased from No data to 3

Description

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011). In that study, the authors showed nominally significant association of 2 markers in LMX1B and a significant decrease in LMX1B expression in the anterior cingulate gyrus of individuals with ASD compared to controls.

4/1/2014
No data
icon
3

Increased from No data to 3

Description

Genetic association has been found between the LMX1B gene and autism in a Caucasian AGRE cohort (Thanseem et al., 2011). In that study, the authors showed nominally significant association of 2 markers in LMX1B and a significant decrease in LMX1B expression in the anterior cingulate gyrus of individuals with ASD compared to controls.

Krishnan Probability Score

Score 0.49444656844603

Ranking 3653/25841 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 0.82273227003236

Ranking 3796/18225 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 0.93327693241845

Ranking 12222/18665 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 2

Ranking 395/461 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 -0.3358924652636

Ranking 17665/20870 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
IDI2 Isopentenyl-diphosphate delta-isomerase 2 Human Protein Binding 91734 Q9BXS1
MAB21L1 Protein mab-21-like 1 Human Protein Binding 4081 Q13394
NPHS2 nephrosis 2, idiopathic, steroid-resistant (podocin) Human DNA Binding 7827 Q9NP85
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