Details for: LMX1B

Gene ID: 4010

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: LMX1B

Ensembl ID: ENSG00000136944

Description: LIM homeobox transcription factor 1 beta

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Chromatin
    (GO:0000785)
  • Dna-binding transcription factor activity
    (GO:0003700)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Dopaminergic neuron differentiation
    (GO:0071542)
  • Dorsal/ventral pattern formation
    (GO:0009953)
  • Metal ion binding
    (GO:0046872)
  • Neuron differentiation
    (GO:0030182)
  • Nucleus
    (GO:0005634)
  • Positive regulation of transcription by rna polymerase ii
    (GO:0045944)
  • Protein binding
    (GO:0005515)
  • Regulation of dna-templated transcription
    (GO:0006355)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Rna polymerase ii transcription regulatory region sequence-specific dna binding
    (GO:0000977)
  • Sequence-specific double-stranded dna binding
    (GO:1990837)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • lung neuroendocrine cell CL1000223
    CSI 3.34
    rCSI 4.94%
    PRS 99.18
  • parietal epithelial cell CL1000452
    CSI 1.67
    rCSI 4.46%
    PRS 99.08
  • podocyte CL0000653
    CSI 1.13
    rCSI 5%
    PRS 99.38

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [LMX1B](/details-gene/4010) (LIM homeobox transcription factor 1 beta) is a protein-coding gene located on chromosome 9q33.3 that encodes a transcription factor crucial for embryonic development. As a member of the LIM-homeodomain family, it plays a fundamental role in specifying dorsal/ventral cell fates during limb, kidney, and eye development. **Overall**, its expression is highly significant in specialized cell types including [lung neuroendocrine cell](/details-cell/CL1000223), and renal cells such as the [parietal epithelial cell](/details-cell/CL1000452) and [podocyte](/details-cell/CL0000653). Clinically, heterozygous loss-of-function mutations in [LMX1B](/details-gene/4010) are the primary cause of Nail-patella syndrome ([161200](https://omim.org/entry/161200)), a pleiotropic autosomal dominant disorder characterized by skeletal abnormalities and nephropathy ([Link](https://doi.org/10.1093/hmg/7.7.1091), [Link](https://doi.org/10.1086/302165)). Certain mutations have also been linked to isolated, hereditary focal segmental glomerulosclerosis (FSGS) without the extra-renal manifestations of Nail-patella syndrome ([Link](https://doi.org/10.1681/asn.2013020171)). ## Cellular Roles and Expression Landscape The expression profile of [LMX1B](/details-gene/4010) highlights its role as a key transcriptional regulator in specific, terminally differentiated cell lineages. **Overall**, the gene shows its highest significance in [lung neuroendocrine cell](/details-cell/CL1000223) (CSI: 3.34), suggesting a potential role in the development or function of this pulmonary cell type. A prominent functional context for [LMX1B](/details-gene/4010) is the kidney glomerulus, where it is a significant marker for both [parietal epithelial cell](/details-cell/CL1000452) (CSI: 1.67) and [podocyte](/details-cell/CL0000653) (CSI: 1.13). The high significance in these two critical cell types of the glomerular filtration barrier is consistent with the well-documented renal pathology, including dysplasia and glomerulopathy, observed in individuals with [LMX1B](/details-gene/4010) mutations ([Link](https://doi.org/10.1038/ng0598-47)). Its function in these cells is likely tied to maintaining their highly specialized architecture and function, which is essential for proper kidney filtration. The expression in these distinct cell types underscores its role as a master regulator of developmental programs rather than a ubiquitous cellular factor. ## Pathways and Molecular Function Functionally, [LMX1B](/details-gene/4010) operates as a DNA-binding transcription factor localized to the nucleus and chromatin. Its molecular activities are centered on regulating gene expression through direct interaction with DNA and other proteins. * **Biological Process:** Gene Ontology annotations confirm its central role in development, including dorsal/ventral pattern formation ([GO:0009953](https://www.ebi.ac.uk/QuickGO/term/GO:0009953)) and neuron differentiation ([GO:0030182](https://www.ebi.ac.uk/QuickGO/term/GO:0030182)), with a specific role in dopaminergic neuron differentiation ([GO:0071542](https://www.ebi.ac.uk/QuickGO/term/GO:0071542)). It is a key positive regulator of transcription by RNA polymerase II ([GO:0045944](https://www.ebi.ac.uk/QuickGO/term/GO:0045944)), which is the mechanistic basis for its developmental functions. * **Molecular Function:** [LMX1B](/details-gene/4010) exhibits sequence-specific double-stranded DNA binding ([GO:1990837](https://www.ebi.ac.uk/QuickGO/term/GO:1990837)) and DNA-binding transcription factor activity specific to RNA polymerase II ([GO:0000981](https://www.ebi.ac.uk/QuickGO/term/GO:0000981)). It also engages in protein binding ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)), consistent with its role in forming transcriptional complexes to regulate target gene expression ([Link](https://doi.org/10.1371/journal.pone.0053122)). * **Cellular Component:** As expected for a transcription factor, it is localized to the nucleus ([GO:0005634](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)) and is associated with chromatin ([GO:0000785](https://www.ebi.ac.uk/QuickGO/term/GO:0000785)). ## Research Directions The established link between [LMX1B](/details-gene/4010) mutations and developmental disorders, particularly nephropathy, provides a clear basis for further investigation into its molecular mechanisms and therapeutic potential. **Testable Hypotheses:** 1. Given its high significance in [podocyte](/details-cell/CL0000653) and its causal role in hereditary FSGS, it is hypothesized that [LMX1B](/details-gene/4010) is a master regulator essential for maintaining the terminal differentiation and structural integrity of podocytes. Haploinsufficiency of [LMX1B](/details-gene/4010) likely disrupts the transcriptional network governing the expression of key podocyte-specific proteins (e.g., those forming the slit diaphragm), leading to foot process effacement and glomerular barrier dysfunction. 2. The high expression of [LMX1B](/details-gene/4010) in [lung neuroendocrine cell](/details-cell/CL1000223) is a less-explored aspect of its biology. It is hypothesized that [LMX1B](/details-gene/4010) plays a critical role in the lineage specification or mature function of these cells, and its dysregulation could contribute to the pathogenesis of neuroendocrine tumors of the lung, such as small cell lung cancer. **Proposed Experiment:** To test the first hypothesis regarding the role of [LMX1B](/details-gene/4010) in podocyte homeostasis, a powerful approach would be to use CRISPR-Cas9 to generate heterozygous loss-of-function mutations in human induced pluripotent stem cells (iPSCs). These edited iPSCs, alongside isogenic wild-type controls, could be differentiated into kidney organoids. Subsequent single-cell RNA sequencing and immunofluorescence analysis of the organoids would allow for a detailed characterization of the effects of [LMX1B](/details-gene/4010) haploinsufficiency on podocyte development, maturation, and the expression of critical structural genes. This model would enable the identification of downstream targets and pathways that are dysregulated, providing insight into the mechanisms of LMX1B-associated nephropathy. **Therapeutic Potential:** As an intracellular transcription factor, [LMX1B](/details-gene/4010) is a challenging direct target for small molecule therapeutics. The associated diseases are caused by loss-of-function mutations, meaning the therapeutic goal would be to restore or augment its activity, not inhibit it. Therefore, future therapeutic strategies are unlikely to involve direct inhibition. Instead, they may focus on gene therapy approaches to deliver a functional copy of the gene to affected cells like podocytes. A more near-term strategy could involve identifying the critical downstream targets of [LMX1B](/details-gene/4010) and developing drugs that modulate these downstream pathways to compensate for the reduced LMX1B activity.

Genular Protein ID: 19951875

Symbol: LMX1B_HUMAN

Name: LIM homeobox transcription factor 1-beta

UniProtKB Accession Codes:

O60663 F8W7W6 O75463 Q5JU95 Q6ISC9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 3 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 11 Ensembl 3 GO 13 Gene3D 2 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 5 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 3 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 RefSeq 2 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9618165

Title: Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.

PubMed ID: 9618165

DOI: 10.1093/hmg/7.7.1091

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9590287

Title: Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome.

PubMed ID: 9590287

DOI: 10.1038/ng0598-47

PubMed ID: 23308148

Title: LMX1B is part of a transcriptional complex with PSPC1 and PSF.

PubMed ID: 23308148

DOI: 10.1371/journal.pone.0053122

PubMed ID: 9837817

Title: Mutation analysis of LMX1B gene in nail-patella syndrome patients.

PubMed ID: 9837817

DOI: 10.1086/302165

PubMed ID: 10571942

Title: Restricted distribution of loss-of-function mutations within the LMX1B genes of nail-patella syndrome patients.

PubMed ID: 10571942

DOI: 10.1002/(sici)1098-1004(199912)14:6<459::aid-humu3>3.0.co;2-9

PubMed ID: 11668639

Title: Twenty-two novel LMX1B mutations identified in nail patella syndrome (NPS) patients.

PubMed ID: 11668639

DOI: 10.1002/humu.1217.abs

PubMed ID: 23687361

Title: LMX1B mutations cause hereditary FSGS without extrarenal involvement.

PubMed ID: 23687361

DOI: 10.1681/asn.2013020171

PubMed ID: 24042019

Title: LMX1B mutation with residual transcriptional activity as a cause of isolated glomerulopathy.

PubMed ID: 24042019

DOI: 10.1093/ndt/gft359

PubMed ID: 26560070

Title: Clinical and histological findings of autosomal dominant renal-limited disease with LMX1B mutation.

PubMed ID: 26560070

DOI: 10.1111/nep.12666

PubMed ID: 28059119

Title: Dysregulation of WTI (-KTS) is associated with the kidney-specific effects of the LMX1B R246Q mutation.

PubMed ID: 28059119

DOI: 10.1038/srep39933

PubMed ID: 32791958

Title: Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report.

PubMed ID: 32791958

DOI: 10.1186/s12882-020-02012-3

PubMed ID: 32356190

Title: Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis.

PubMed ID: 32356190

DOI: 10.1007/s00467-020-04564-w

Sequence Information:

  • Length: 402
  • Mass: 44917
  • Checksum: E59FC36C39C7C9A3
  • Sequence:
    • MDIATGPESL ERCFPRGQTD CAKMLDGIKM EEHALRPGPA TLGVLLGSDC PHPAVCEGCQ 
RPISDRFLMR VNESSWHEEC LQCAACQQAL TTSCYFRDRK LYCKQDYQQL FAAKCSGCME 
KIAPTEFVMR ALECVYHLGC FCCCVCERQL RKGDEFVLKE GQLLCKGDYE KEKDLLSSVS 
PDESDSVKSE DEDGDMKPAK GQGSQSKGSG DDGKDPRRPK RPRTILTTQQ RRAFKASFEV 
SSKPCRKVRE TLAAETGLSV RVVQVWFQNQ RAKMKKLARR HQQQQEQQNS QRLGQEVLSS 
RMEGMMASYT PLAPPQQQIV AMEQSPYGSS DPFQQGLTPP QMPGDHMNPY GNDSIFHDID 
SDTSLTSLSD CFLGSSDVGS LQARVGNPID RLYSMQSSYF AS

Genular Protein ID: 1744571347

Symbol: Q6ISE0_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6ISE0

Database IDs:

ARBA 9 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 3 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 5 Gene3D 2 InterPro 5 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 6 PROSITE-ProRule 2 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 RuleBase 1 SAM 1 SMART 2 SUPFAM 2

Citations:

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 377
  • Mass: 42165
  • Checksum: 342C0EAD3206548A
  • Sequence:
    • DGIKMEEHAL RPGPATLGVL LGSDCPHPAV CEGCQRPISD RFLMRVNESS WHEECLQCAA 
CQQALTTSCY FRDRKLYCKQ DYQQLFAAKC SGCMEKIAPT EFVMRALECV YHLGCFCCCV 
CERQLRKGDE FVLKEGQLLC KGDYEKEKDL LSSVSPDESD SVKSEDEDGD MKPAKGQGSQ 
SKGSGDDGKD PRRPKRPRTI LTTQQRRAFK ASFEVSSKPC RKVRETLAAE TGLSVRVVQV 
WFQNQRAKMK KLARRHQQQQ EQQNSQRLGQ EVLSSRMEGM MASYTPLAPP QQQIVAMEQS 
PYGSSDPFQQ GLTPPQMPGD HMNPYGNDSI FHDIDSDTSL TSLSDCFLGS SDVGSLQARV 
GNPIDRLYSM QSSYFAS

Genular Protein ID: 3942536012

Symbol: B7ZLH2_HUMAN

Name: N/A

UniProtKB Accession Codes:

B7ZLH2

Database IDs:

ARBA 9 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 3 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 5 Gene3D 2 HOGENOM 1 InterPro 5 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 6 PROSITE-ProRule 2 PeptideAtlas 1 Pfam 2 PharmGKB 1 ProteomicsDB 1 RefSeq 1 RuleBase 1 SAM 1 SMART 2 SMR 1 SUPFAM 2 UCSC 1

Citations:

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 383
  • Mass: 42572
  • Checksum: 28C51599518CF4FC
  • Sequence:
    • MLDGIKMEEH ALRPGPATLG VLLGSDCPHP AVCEGCQRPI SDRFLMRVNE SSWHEECLQC 
AACQQALTTS CYFRDRKLYC KQDYQQLFAA KCSGCMEKIA PTEFVMRALE CVYHLGCFCC 
CVCERQLRKG DEFVLKEGQL LCKGDYEKEK DLLSSVSPDE SDSVKSEDED GDMKPAKGQG 
SQSKGSGDDG KDPRRPKRPR TILTTQQRRA FKASFEVSSK PCRKVRETLA AETGLSVRVV 
QVWFQNQRAK MKKLARRHQQ QQEQQNSQRL GQGEPGPGQG LGQEVLSSRM EGMMASYTPL 
APPQQQIVAM EQSPYGSSDP FQQGLTPPQM PGNDSIFHDI DSDTSLTSLS DCFLGSSDVG 
SLQARVGNPI DRLYSMQSSY FAS