Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEEYD5L)

DOT Name LIM homeobox transcription factor 1-alpha (LMX1A)
Synonyms LIM/homeobox protein 1.1; LMX-1.1; LIM/homeobox protein LMX1A
Gene Name LMX1A
Related Disease
Schizophrenia ( )
Advanced cancer ( )
Autosomal dominant nonsyndromic hearing loss 7 ( )
Benign neoplasm ( )
Bipolar disorder ( )
Bladder cancer ( )
Cervical cancer ( )
Cervical carcinoma ( )
Epithelial ovarian cancer ( )
Obsessive compulsive disorder ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Parkinson disease ( )
Sensorineural hearing loss disorder ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Neoplasm ( )
Parkinsonian disorder ( )
Deafness ( )
Gastric cancer ( )
Stomach cancer ( )
UniProt ID
LMX1A_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00046 ; PF00412
Sequence
MLDGLKMEENFQSAIDTSASFSSLLGRAVSPKSVCEGCQRVILDRFLLRLNDSFWHEQCV
QCASCKEPLETTCFYRDKKLYCKYDYEKLFAVKCGGCFEAIAPNEFVMRAQKSVYHLSCF
CCCVCERQLQKGDEFVLKEGQLLCKGDYEKERELLSLVSPAASDSGKSDDEESLCKSAHG
AGKGTAEEGKDHKRPKRPRTILTTQQRRAFKASFEVSSKPCRKVRETLAAETGLSVRVVQ
VWFQNQRAKMKKLARRQQQQQQDQQNTQRLSSAQTNGGGSAGMEGIMNPYTALPTPQQLL
AIEQSVYSSDPFRQGLTPPQMPGDHMHPYGAEPLFHDLDSDDTSLSNLGDCFLATSEAGP
LQSRVGNPIDHLYSMQNSYFTS
Function
Acts as a transcriptional activator by binding to an A/T-rich sequence, the FLAT element, in the insulin gene promoter. Required for development of the roof plate and, in turn, for specification of dorsal cell fates in the CNS and developing vertebrae.
Tissue Specificity Isoform 1 is expressed in many tissues. Not found in heart, liver, spleen and testis. Relatively highly expressed in fetal brain. Isoform LMX1A-4AB is expressed in testis.

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Schizophrenia DISSRV2N Definitive Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Autosomal dominant nonsyndromic hearing loss 7 DISG3IHA Strong Autosomal dominant [3]
Benign neoplasm DISDUXAD Strong Biomarker [2]
Bipolar disorder DISAM7J2 Strong Biomarker [1]
Bladder cancer DISUHNM0 Strong Posttranslational Modification [4]
Cervical cancer DISFSHPF Strong Biomarker [5]
Cervical carcinoma DIST4S00 Strong Biomarker [5]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [6]
Obsessive compulsive disorder DIS1ZMM2 Strong Genetic Variation [7]
Ovarian cancer DISZJHAP Strong Biomarker [6]
Ovarian neoplasm DISEAFTY Strong Biomarker [6]
Parkinson disease DISQVHKL Strong Posttranslational Modification [8]
Sensorineural hearing loss disorder DISJV45Z Strong Biomarker [9]
Urinary bladder cancer DISDV4T7 Strong Posttranslational Modification [4]
Urinary bladder neoplasm DIS7HACE Strong Posttranslational Modification [4]
Neoplasm DISZKGEW moderate Altered Expression [10]
Parkinsonian disorder DISHGY45 Disputed Biomarker [11]
Deafness DISKCLH4 Limited Biomarker [9]
Gastric cancer DISXGOUK Limited Biomarker [10]
Stomach cancer DISKIJSX Limited Biomarker [10]
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⏷ Show the Full List of 21 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved LIM homeobox transcription factor 1-alpha (LMX1A) increases the Hepatotoxicity ADR of Acetaminophen. [17]
NAPQI DM8F5LR Investigative LIM homeobox transcription factor 1-alpha (LMX1A) affects the response to substance of NAPQI. [17]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of LIM homeobox transcription factor 1-alpha (LMX1A). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of LIM homeobox transcription factor 1-alpha (LMX1A). [13]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of LIM homeobox transcription factor 1-alpha (LMX1A). [14]
Rofecoxib DM3P5DA Approved Rofecoxib increases the expression of LIM homeobox transcription factor 1-alpha (LMX1A). [15]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of LIM homeobox transcription factor 1-alpha (LMX1A). [16]
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References

1 Polymorphisms of dopamine pathway genes NRG1 and LMX1A are associated with cognitive performance in bipolar disorder.Bipolar Disord. 2015 Dec;17(8):859-68. doi: 10.1111/bdi.12347. Epub 2015 Nov 3.
2 An epigenetic marker panel for screening and prognostic prediction of ovarian cancer.Int J Cancer. 2009 Jan 15;124(2):387-93. doi: 10.1002/ijc.23957.
3 Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction. Hum Genet. 2018 May;137(5):389-400. doi: 10.1007/s00439-018-1880-5. Epub 2018 May 12.
4 Methylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population. PLoS One. 2012;7(4):e35175.
5 Methylation of the hsa-miR-124, SOX1, TERT, and LMX1A genes as biomarkers for precursor lesions in cervical cancer.Gynecol Oncol. 2018 Sep;150(3):545-551. doi: 10.1016/j.ygyno.2018.06.014. Epub 2018 Jun 28.
6 LIM-homeobox transcription factor 1, alpha (LMX1A) inhibits tumourigenesis, epithelial-mesenchymal transition and stem-like properties of epithelial ovarian cancer.Gynecol Oncol. 2013 Mar;128(3):475-82. doi: 10.1016/j.ygyno.2012.12.018. Epub 2012 Dec 24.
7 Gene variations in PBX1, LMX1A and SLITRK1 are associated with obsessive-compulsive disorder and its clinical features.J Clin Neurosci. 2019 Mar;61:180-185. doi: 10.1016/j.jocn.2018.10.042. Epub 2018 Oct 28.
8 Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons.Proc Natl Acad Sci U S A. 2016 Jul 26;113(30):E4387-96. doi: 10.1073/pnas.1520387113. Epub 2016 Jul 12.
9 A variant in LMX1A causes autosomal recessive severe-to-profound hearing impairment.Hum Genet. 2018 Jul;137(6-7):471-478. doi: 10.1007/s00439-018-1899-7. Epub 2018 Jul 3.
10 LMX1A inhibits C-Myc expression through ANGPTL4 to exert tumor suppressive role in gastric cancer.PLoS One. 2019 Sep 26;14(9):e0221640. doi: 10.1371/journal.pone.0221640. eCollection 2019.
11 Isolation of LMX1a Ventral Midbrain Progenitors Improves the Safety and Predictability of Human Pluripotent Stem Cell-Derived Neural Transplants in Parkinsonian Disease.J Neurosci. 2019 Nov 27;39(48):9521-9531. doi: 10.1523/JNEUROSCI.1160-19.2019. Epub 2019 Oct 22.
12 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
13 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
14 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
15 Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
16 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
17 Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.