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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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LMX1A
LIM homeobox transcription factor 1 alpha
Chromosome 1 Β· 1q23.3
NCBI Gene: 4009Ensembl: ENSG00000162761.14HGNC: HGNC:6653UniProt: Q8TE12
56PubMed Papers
21Diseases
0Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
sequence-specific double-stranded DNA bindingprotein bindingDNA-binding transcription activator activity, RNA polymerase II-specificRNA polymerase II transcription regulatory region sequence-specific DNA bindingautosomal dominant nonsyndromic hearing loss 7autosomal dominant nonsyndromic hearing lossSensorineural hearing impairmentAbnormality of the skeletal system
✦AI Summary

LMX1A (LIM homeobox transcription factor 1 alpha) is a transcriptional activator that plays crucial roles in neural development and disease pathogenesis. The protein functions as a sequence-specific DNA-binding transcription factor that binds to A/T-rich sequences and activates insulin gene transcription 1. In neural development, LMX1A is essential for dopaminergic neuron specification and ventral midbrain patterning, though forced overexpression can paradoxically induce dorsal neural fates and disrupt proper midbrain dopaminergic neuron development 2. The transcription factor is critical for maintaining adult dopaminergic neurons and shows persistent expression in substantia nigra and ventral tegmental area 3. LMX1A demonstrates tumor suppressor functions in gastric cancer, where it is downregulated and targeted by microRNA-9 for degradation, promoting cancer cell progression 4. The protein is also subject to post-translational regulation through ubiquitination by RNF38, which promotes autophagy and drug resistance in acute myeloid leukemia 5. Genetic variants in LMX1A show associations with obsessive-compulsive disorder symptoms 6 and have been identified as novel risk loci for Alzheimer's disease 7. For therapeutic applications, LMX1A-positive progenitors show promise for Parkinson's disease cell replacement therapy 8.

Sources cited
1
LMX1A activates insulin gene transcription by binding to A/T-rich sequences
PMID: 12062816
2
Forced LMX1A expression induces dorsal neural fates and disrupts ventral midbrain dopaminergic neuron development
PMID: 38759646
3
LMX1A persists in mature dopaminergic neurons and is involved in adult neuronal homeostasis
PMID: 26526610
4
LMX1A functions as tumor suppressor in gastric cancer and is targeted by microRNA-9
PMID: 30262143
5
RNF38 regulates LMX1A through ubiquitination, affecting autophagy and drug resistance in acute myeloid leukemia
PMID: 39604755
6
LMX1A variants are associated with obsessive-compulsive disorder symptoms
PMID: 30377043
7
LMX1A locus identified as novel Alzheimer's disease risk factor
PMID: 39998322
8
LMX1A-positive progenitors show therapeutic potential for Parkinson's disease
PMID: 31641054
Disease Associationsβ“˜21
autosomal dominant nonsyndromic hearing loss 7Open Targets
0.70Moderate
autosomal dominant nonsyndromic hearing lossOpen Targets
0.62Moderate
Sensorineural hearing impairmentOpen Targets
0.36Weak
Abnormality of the skeletal systemOpen Targets
0.36Weak
neurodegenerative diseaseOpen Targets
0.34Weak
sensorineural hearing lossOpen Targets
0.33Weak
facial morphologyOpen Targets
0.33Weak
age-related hearing impairmentOpen Targets
0.26Weak
benign prostatic hyperplasiaOpen Targets
0.24Weak
type 1 diabetes mellitusOpen Targets
0.23Weak
iron metabolism diseaseOpen Targets
0.22Weak
hemolytic anemiaOpen Targets
0.21Weak
ShockOpen Targets
0.20Weak
hearing lossOpen Targets
0.19Weak
hypertensionOpen Targets
0.18Weak
substance-related disorderOpen Targets
0.18Weak
vestibular neuronitisOpen Targets
0.16Weak
kidney diseaseOpen Targets
0.16Weak
preeclampsiaOpen Targets
0.15Weak
spermatoceleOpen Targets
0.15Weak
Deafness, autosomal dominant, 7UniProt
Pathogenic Variants8
NM_177398.4(LMX1A):c.390_391delinsAT (p.Lys131Ter)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 7
β˜…β˜†β˜†β˜†2025β†’ Residue 131
NM_177398.4(LMX1A):c.596G>A (p.Arg199Lys)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 7
β˜…β˜†β˜†β˜†2025β†’ Residue 199
NM_177398.4(LMX1A):c.937C>T (p.Arg313Ter)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 7
β˜…β˜†β˜†β˜†2023β†’ Residue 313
NM_177398.4(LMX1A):c.622C>T (p.Arg208Ter)Pathogenic
Autosomal dominant nonsyndromic hearing loss 7
β˜…β˜†β˜†β˜†2022β†’ Residue 208
NM_177398.4(LMX1A):c.595A>G (p.Arg199Gly)Pathogenic
Autosomal dominant nonsyndromic hearing loss 7
β˜…β˜†β˜†β˜†2022β†’ Residue 199
NM_177398.4(LMX1A):c.331del (p.Gln111fs)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 7
β˜…β˜†β˜†β˜†2022β†’ Residue 111
NM_177398.4(LMX1A):c.290G>C (p.Cys97Ser)Pathogenic
Autosomal dominant nonsyndromic hearing loss 7
β˜†β˜†β˜†β˜†2020β†’ Residue 97
NM_177398.4(LMX1A):c.721G>C (p.Val241Leu)Pathogenic
Autosomal dominant nonsyndromic hearing loss 7
β˜†β˜†β˜†β˜†2020β†’ Residue 241
View on ClinVar β†—
Related Genes
NEUROG2Protein interaction98%NKX2-2Protein interaction87%MSX1Protein interaction81%ASCL1Protein interaction80%FOXA2Protein interaction80%WNT1Protein interaction76%
Tissue Expression6 tissues
Liver
100%
Brain
50%
Lung
25%
Bone Marrow
25%
Ovary
0%
Heart
0%
Gene Interaction Network
Click a node to explore
LMX1ANEUROG2NKX2-2MSX1ASCL1FOXA2WNT1
PROTEIN STRUCTURE
Preparing viewer…
PDB8IK5 Β· 1.99 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.48Moderately Constrained
pLIβ“˜
0.99Intolerant
Observed/Expected LoF0.31 [0.21–0.48]
RankingsWhere LMX1A stands among ~20K protein-coding genes
  • #8,094of 20,598
    Most Researched56
  • #3,083of 5,498
    Most Pathogenic Variants8
  • #2,760of 17,882
    Most Constrained (LOEUF)0.48 Β· top quartile
Genes detectedLMX1A
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Identification of 16 novel Alzheimer's disease loci using multi-ancestry meta-analyses.
PMID: 39998322
Alzheimers Dement Β· 2025
1.00
2
Forced LMX1A expression induces dorsal neural fates and disrupts patterning of human embryonic stem cells into ventral midbrain dopaminergic neurons.
PMID: 38759646
Stem Cell Reports Β· 2024
0.90
3
Cell fate determination, neuronal maintenance and disease state: The emerging role of transcription factors Lmx1a and Lmx1b.
PMID: 26526610
FEBS Lett Β· 2015
0.80
4
Cloning, expression and genomic structure of human LMX1A, and variant screening in Pima Indians.
PMID: 12062816
Gene Β· 2002
0.70
5
RNF38 promotes gilteritinib resistance in acute myeloid leukemia via inducing autophagy by regulating ubiquitination of LMX1A.
PMID: 39604755
Cell Biol Toxicol Β· 2024
0.60