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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LHX5
LIM homeobox 5
Chromosome 12 · 12q24.13
NCBI Gene: 64211Ensembl: ENSG00000089116.4HGNC: HGNC:14216UniProt: Q9H2C1
10PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
sequence-specific double-stranded DNA bindingprotein bindingneuron differentiationnucleusmathematical abilitychronic obstructive pulmonary diseasecardiac arrhythmiabronchial disease
✦AI Summary

LHX5 (LIM homeobox 5) is a transcription factor that plays essential roles in central nervous system development, particularly in neuronal differentiation and migration 1. The protein contains LIM and homeobox domains and functions as a DNA-binding transcription factor that regulates RNA polymerase II-mediated transcription. LHX5 is critical for hippocampal morphogenesis, where it controls precursor cell proliferation and ensures proper neuronal differentiation and migration; mice lacking Lhx5 show severely disorganized brain morphology and cognitive/motor coordination defects 2. The gene also functions in cerebellar development, working alongside Lhx1 to control Purkinje cell differentiation, with double mutants showing severe reduction in Purkinje cell numbers 3. LHX5 exhibits dynamic expression patterns during forebrain development, initially expressed broadly in the diencephalic primordium before becoming restricted to specific regions in an alternating pattern with Dlx genes 4. Recent genome-wide association studies have identified LHX5-AS1 (antisense RNA near LHX5) as a novel risk locus for late-onset Alzheimer's disease, suggesting potential involvement in neurodegeneration 5. The gene is also implicated as a prognostic marker in breast cancer through chr12 remodeling pathways 6.

Sources cited
1
LHX5 plays essential role in neuronal differentiation and migration during CNS development; mice lacking Lhx5 show disorganized brain morphology and cognitive/motor defects
PMID: 11137295
2
LHX5 is essential for hippocampal morphogenesis, controlling precursor cell proliferation and neuronal differentiation/migration
PMID: 10325223
3
LHX5 works with Lhx1 to control Purkinje cell differentiation in cerebellar development
PMID: 17664423
4
LHX5 shows dynamic expression patterns in forebrain development, initially broad then restricted in alternating pattern with Dlx genes
PMID: 9022063
5
LHX5-AS1 identified as novel risk locus for late-onset Alzheimer's disease in multi-ancestry GWAS
PMID: 40676597
6
LHX5 implicated as prognostic marker in breast cancer through chromatin remodeling pathways
PMID: 40317384
Disease Associationsⓘ20
mathematical abilityOpen Targets
0.41Moderate
chronic obstructive pulmonary diseaseOpen Targets
0.25Weak
cardiac arrhythmiaOpen Targets
0.25Weak
bronchial diseaseOpen Targets
0.24Weak
smoking initiationOpen Targets
0.23Weak
Alzheimer diseaseOpen Targets
0.22Weak
type 2 diabetes mellitusOpen Targets
0.22Weak
iron metabolism diseaseOpen Targets
0.21Weak
exostosisOpen Targets
0.19Weak
male infertilityOpen Targets
0.19Weak
smoking cessationOpen Targets
0.18Weak
Hernia of the abdominal wallOpen Targets
0.17Weak
gastric cancerOpen Targets
0.16Weak
Abnormal nasolacrimal system morphologyOpen Targets
0.15Weak
complicationOpen Targets
0.08Suggestive
hemorrhageOpen Targets
0.08Suggestive
glioblastoma multiformeOpen Targets
0.07Suggestive
HypocalcemiaOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.05Suggestive
Chudley-McCullough syndromeOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
OTPShared pathway100%LHX9Shared pathway100%NIF3L1Shared pathway100%LHX4Shared pathway100%CCNKProtein interaction84%VXNShared pathway50%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
40%
Lung
0%
Heart
0%
Ovary
0%
Liver
0%
Gene Interaction Network
Click a node to explore
LHX5OTPLHX9NIF3L1LHX4CCNKVXN
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9H2C1
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.42Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.21 [0.12–0.42]
RankingsWhere LHX5 stands among ~20K protein-coding genes
  • #17,092of 20,598
    Most Researched10
  • #2,218of 17,882
    Most Constrained (LOEUF)0.42 · top quartile
Genes detectedLHX5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Genomic structure, chromosomal localization and expression of the human LIM-homeobox gene LHX5.
PMID: 11137295
Gene · 2000
1.00
2
Control of hippocampal morphogenesis and neuronal differentiation by the LIM homeobox gene Lhx5.
PMID: 10325223
Science · 1999
0.90
3
Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.
PMID: 40676597
Genome Biol · 2025
0.80
4
Mutational analysis of two positional candidate susceptibility genes for bipolar disorder on chromosome 12q23-q24: phenylalanine hydroxylase and human LIM-homeobox LHX5.
PMID: 12782966
Psychiatr Genet · 2003
0.70
5
Similarities and differences in the forebrain expression of Lhx1 and Lhx5 between chicken and mouse: Insights for understanding telencephalic development and evolution.
PMID: 20589911
J Comp Neurol · 2010
0.60