This gene encodes a member of 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 serotoner... See more...

Aliases for LMX1B Gene

Aliases for LMX1B Gene

  • LIM Homeobox Transcription Factor 1 Beta 2 3 5
  • LIM Homeobox Transcription Factor 1-Beta 3 4
  • LIM/Homeobox Protein 1.2 3 4
  • LMX-1.2 3 4
  • LIM Homeobox Transcription Factor 1, Beta 2
  • LIM/Homeobox Protein LMX1B 4
  • LMX1.2 3
  • NPS1 3

External Ids for LMX1B Gene

Previous HGNC Symbols for LMX1B Gene

  • NPS1

Previous GeneCards Identifiers for LMX1B Gene

  • GC09P120491
  • GC09P121023
  • GC09P122830
  • GC09P124752
  • GC09P126456
  • GC09P128416
  • GC09P129376
  • GC09P098989

Summaries for LMX1B Gene

Entrez Gene Summary for LMX1B Gene

  • This gene encodes a member of 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. Mutations in this gene are associated with nail-patella syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

GeneCards Summary for LMX1B Gene

LMX1B (LIM Homeobox Transcription Factor 1 Beta) is a Protein Coding gene. Diseases associated with LMX1B include Nail-Patella Syndrome and Nail-Patella-Like Renal Disease. Among its related pathways are Primary Focal Segmental Glomerulosclerosis FSGS and Dopaminergic Neurogenesis. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and sequence-specific DNA binding. An important paralog of this gene is LMX1A.

UniProtKB/Swiss-Prot Summary for LMX1B Gene

  • Essential for the specification of dorsal limb fate at both the zeugopodal and autopodal levels.

Gene Wiki entry for LMX1B Gene

Additional gene information for LMX1B Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for LMX1B Gene

Genomics for LMX1B Gene

GeneHancer (GH) Regulatory Elements for LMX1B Gene

Promoters and enhancers for LMX1B Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH09J126613 Promoter/Enhancer 1.1 Ensembl ENCODE 750.6 +0.0 43 2.2 MNT POLR2A ELF3 ELF1 MYC KLF14 GLIS2 ZIC2 ZBTB8A ZEB2 ENSG00000224842 LOC105376277 LMX1B ENSG00000238010
GH09J126615 Promoter/Enhancer 0.9 Ensembl ENCODE 750.6 +1.5 1458 0.6 MNT SP1 ELF3 ZNF561 ZFX EZH2 RNF2 ELF1 ZNF687 CTCF LMX1B ENSG00000238010
GH09J126612 Promoter 0.7 Ensembl 750.6 -1.5 -1542 0.2 ZEB2 ZBTB20 EZH2 ZXDB ZBTB10 ZNF335 HIC1 ZFP64 ZFX ENSG00000224842 LOC105376277 LMX1B piR-42491-237
GH09J126650 Enhancer 0.9 Ensembl CraniofacialAtlas 16.9 +36.1 36058 0.6 SP7 GLIS2 ZIC2 ZNF639 ZEB2 ZNF561 ZSCAN5C ZXDB ZNF10 OSR2 LMX1B ENSG00000224842 ENSG00000252985 ENSG00000238010 piR-38210
GH09J126587 Enhancer 1 Ensembl ENCODE CraniofacialAtlas 12.4 -26.4 -26442 2 ZBTB6 ZIC2 ZBTB8A RXRB RFX1 ZNF205 TGIF2 RNF2 SAP130 ZSCAN29 ENSG00000224842 LMX1B ENSG00000226078 ENSG00000252985 HSALNG0074449 piR-42491-237
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LMX1B on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the LMX1B gene promoter:
  • HEN1
  • NF-kappaB
  • NF-kappaB1
  • STAT1
  • STAT1alpha
  • STAT1beta
  • STAT2
  • STAT3
  • STAT4
  • STAT5A

Genomic Locations for LMX1B Gene

Genomic Locations for LMX1B Gene
chr9:126,614,443-126,701,032
(GRCh38/hg38)
Size:
86,590 bases
Orientation:
Plus strand
chr9:129,376,722-129,463,311
(GRCh37/hg19)
Size:
86,590 bases
Orientation:
Plus strand

Genomic View for LMX1B Gene

Genes around LMX1B on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LMX1B Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LMX1B Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LMX1B Gene

Proteins for LMX1B Gene

  • Protein details for LMX1B Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O60663-LMX1B_HUMAN
    Recommended name:
    LIM homeobox transcription factor 1-beta
    Protein Accession:
    O60663
    Secondary Accessions:
    • F8W7W6
    • O75463
    • Q5JU95
    • Q6ISC9

    Protein attributes for LMX1B Gene

    Size:
    402 amino acids
    Molecular mass:
    44917 Da
    Quaternary structure:
    • Interacts with DHX9 (PubMed:23308148).
    SequenceCaution:
    • Sequence=AAC27294.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAC39738.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAH69601.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAI12121.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAI13492.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=EAW87642.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for LMX1B Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for LMX1B Gene

Post-translational modifications for LMX1B Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for LMX1B Gene

No data available for DME Specific Peptides for LMX1B Gene

Domains & Families for LMX1B Gene

Gene Families for LMX1B Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for LMX1B Gene

Suggested Antigen Peptide Sequences for LMX1B Gene

GenScript: Design optimal peptide antigens:
  • LMX1B protein (B7ZLH2_HUMAN)
  • LIM/homeobox protein LMX1B (LMX1B_HUMAN)
  • LMX1B protein (Q6ISE0_HUMAN)
genes like me logo Genes that share domains with LMX1B: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for LMX1B Gene

Function for LMX1B Gene

Molecular function for LMX1B Gene

UniProtKB/Swiss-Prot Function:
Essential for the specification of dorsal limb fate at both the zeugopodal and autopodal levels.
GENATLAS Biochemistry:
transcriptional regulator of the LIM-homeo domain,LMX1A related gene,highly expressed in renal development and skeletal patterning,found in adult testis,thyroid,duodenum,skeletal muscle,pancreatic islets,involved in dorsal-ventral limb patterning and kidney development

Phenotypes From GWAS Catalog for LMX1B Gene

Gene Ontology (GO) - Molecular Function for LMX1B Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding ISS --
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISS,NAS 19274049
GO:0003677 DNA binding IEA --
GO:0003700 DNA-binding transcription factor activity IDA 10767331
GO:0005515 protein binding IPI 12792813
genes like me logo Genes that share ontologies with LMX1B: view
genes like me logo Genes that share phenotypes with LMX1B: view

Human Phenotype Ontology for LMX1B Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for LMX1B Gene

MGI Knock Outs for LMX1B:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LMX1B

Clone Products

  • Addgene plasmids for LMX1B

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for LMX1B Gene

Localization for LMX1B Gene

Subcellular locations from UniProtKB/Swiss-Prot for LMX1B Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for LMX1B gene
Compartment Confidence
nucleus 5
cytosol 2
extracellular 1
cytoskeleton 1
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for LMX1B Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA,IDA 10767331
genes like me logo Genes that share ontologies with LMX1B: view

Pathways & Interactions for LMX1B Gene

genes like me logo Genes that share pathways with LMX1B: view

Gene Ontology (GO) - Biological Process for LMX1B Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001701 in utero embryonic development NAS 12792813
GO:0006355 regulation of transcription, DNA-templated IDA 10767331
GO:0007275 multicellular organism development NAS 9590287
GO:0009953 dorsal/ventral pattern formation ISS --
GO:0030182 neuron differentiation ISS --
genes like me logo Genes that share ontologies with LMX1B: view

No data available for SIGNOR curated interactions for LMX1B Gene

Drugs & Compounds for LMX1B Gene

(3) Drugs for LMX1B Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for LMX1B Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with LMX1B: view

Transcripts for LMX1B Gene

mRNA/cDNA for LMX1B Gene

(3) REFSEQ mRNAs :
(10) Additional mRNA sequences :
(8) Selected AceView cDNA sequences:
(4) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LMX1B

Clone Products

  • Addgene plasmids for LMX1B

Alternative Splicing Database (ASD) splice patterns (SP) for LMX1B Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10
SP1: - - -
SP2: - -
SP3:

Relevant External Links for LMX1B Gene

GeneLoc Exon Structure for
LMX1B
ECgene alternative splicing isoforms for
LMX1B

Expression for LMX1B Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for LMX1B Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for LMX1B Gene

This gene is overexpressed in Breast - Mammary Tissue (x9.6), Heart - Atrial Appendage (x4.9), Skin - Sun Exposed (Lower leg) (x4.8), and Brain - Spinal cord (cervical c-1) (x4.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for LMX1B Gene



NURSA nuclear receptor signaling pathways regulating expression of LMX1B Gene:

LMX1B

SOURCE GeneReport for Unigene cluster for LMX1B Gene:

Hs.129133

mRNA Expression by UniProt/SwissProt for LMX1B Gene:

O60663-LMX1B_HUMAN
Tissue specificity: Expressed in most tissues. Highest levels in testis, thyroid, duodenum, skeletal muscle, and pancreatic islets.

Evidence on tissue expression from TISSUES for LMX1B Gene

  • Nervous system(2.3)
  • Kidney(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for LMX1B Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • eye
  • eyelid
  • face
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • skull
Thorax:
  • chest wall
  • clavicle
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • kidney
Pelvis:
  • pelvis
  • ureter
  • urinary bladder
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • nail
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • coagulation system
  • red blood cell
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with LMX1B: view

No data available for Protein differential expression in normal tissues and Protein tissue co-expression partners for LMX1B Gene

Orthologs for LMX1B Gene

This gene was present in the common ancestor of animals.

Orthologs for LMX1B Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia LMX1B 33 32
  • 99.16 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia LMX1B 33
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia LMX1B 33 32
  • 95.41 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia LMX1B 33
  • 95 (a)
OneToOne
cow
(Bos Taurus)
Mammalia LMX1B 33 32
  • 94.16 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Lmx1b 32
  • 93.53 (n)
mouse
(Mus musculus)
Mammalia Lmx1b 17 33 32
  • 93.37 (n)
chicken
(Gallus gallus)
Aves LMX1B 33 32
  • 80.11 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia LMX1B 33
  • 89 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100495130 32
  • 78.67 (n)
Str.18490 32
zebrafish
(Danio rerio)
Actinopterygii lmx1ba 33
  • 80 (a)
OneToMany
lmx1bb 33 32
  • 79.64 (n)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta CG4328 33 34
  • 28 (a)
ManyToMany
CG32105 33
  • 24 (a)
ManyToMany
worm
(Caenorhabditis elegans)
Secernentea lim-6 33 34 32
  • 49.11 (n)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 32 (a)
ManyToMany
-- 33
  • 24 (a)
ManyToMany
Cin.235 32
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.235 32
Species where no ortholog for LMX1B was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for LMX1B Gene

ENSEMBL:
Gene Tree for LMX1B (if available)
TreeFam:
Gene Tree for LMX1B (if available)
Aminode:
Evolutionary constrained regions (ECRs) for LMX1B: view image

Paralogs for LMX1B Gene

(14) SIMAP similar genes for LMX1B Gene using alignment to 3 proteins:

  • LMX1B_HUMAN
  • B7ZLH2_HUMAN
  • Q6ISE0_HUMAN
genes like me logo Genes that share paralogs with LMX1B: view

Variants for LMX1B Gene

Sequence variations from dbSNP and Humsavar for LMX1B Gene

SNP ID Clin Chr 09 pos Variation AA Info Type
rs10115304 benign, not specified, Nail-patella syndrome 126,696,349(+) C/A/T coding_sequence_variant, missense_variant, synonymous_variant
rs10115373 benign, Nail-patella syndrome 126,696,478(+) G/A/C 3_prime_UTR_variant
rs10115393 benign, Nail-patella syndrome 126,696,530(+) G/A 3_prime_UTR_variant
rs10120414 benign, Nail-patella syndrome 126,698,844(+) T/C 3_prime_UTR_variant
rs10121481 benign, Nail-patella syndrome 126,696,502(+) A/G 3_prime_UTR_variant

Structural Variations from Database of Genomic Variants (DGV) for LMX1B Gene

Variant ID Type Subtype PubMed ID
dgv1234n67 CNV gain 20364138
dgv12868n54 CNV loss 21841781
dgv12869n54 CNV loss 21841781
esv2659178 CNV deletion 23128226
esv2739046 CNV deletion 23290073
esv3576705 CNV gain 25503493
esv3621766 CNV gain 21293372
esv3621769 CNV loss 21293372
nsv1113016 CNV deletion 24896259
nsv466568 CNV loss 19166990
nsv517494 CNV loss 19592680
nsv528719 CNV loss 19592680
nsv615316 CNV loss 21841781
nsv6718 CNV deletion 18451855
nsv825080 CNV gain 20364138
nsv825083 CNV gain 20364138
nsv831723 CNV gain+loss 17160897
nsv951764 CNV deletion 24416366

Variation tolerance for LMX1B Gene

Residual Variation Intolerance Score: 16.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.78; 16.37% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for LMX1B Gene

Human Gene Mutation Database (HGMD)
LMX1B
SNPedia medical, phenotypic, and genealogical associations of SNPs for
LMX1B

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LMX1B Gene

Disorders for LMX1B Gene

MalaCards: The human disease database

(12) MalaCards diseases for LMX1B Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
nail-patella syndrome
  • nps
nail-patella-like renal disease
  • glomerular basement membrane disease, nail-patella syndrome type
epileptic encephalopathy, early infantile, 4
  • eiee4
9q33.3q34.11 microdeletion syndrome
  • del(9)(q33.3q34.11)
genitopatellar syndrome
  • gps
- elite association - COSMIC cancer census association via MalaCards
Search LMX1B in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

LMX1B_HUMAN
  • Nail-patella syndrome (NPS) [MIM:161200]: Disease that cause abnormal skeletal patterning and renal dysplasia. {ECO:0000269 PubMed:10571942, ECO:0000269 PubMed:11668639, ECO:0000269 PubMed:9590287, ECO:0000269 PubMed:9618165, ECO:0000269 PubMed:9837817}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for LMX1B

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with LMX1B: view

No data available for Genatlas for LMX1B Gene

Publications for LMX1B Gene

  1. Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. (PMID: 9590287) Dreyer SD … Lee B (Nature genetics 1998) 2 3 4 23 56
  2. The transcription factor PITX3 is associated with sporadic Parkinson's disease. (PMID: 17905480) Fuchs J … Gasser T (Neurobiology of aging 2009) 3 23 43 56
  3. Genetic risk for primary open-angle glaucoma determined by LMX1B haplotypes. (PMID: 18952915) Park S … Sowden JC (Investigative ophthalmology & visual science 2009) 3 23 43 56
  4. Do polymorphisms in transcription factors LMX1A and LMX1B influence the risk for Parkinson's disease? (PMID: 19189040) Bergman O … Nissbrandt H (Journal of neural transmission (Vienna, Austria : 1996) 2009) 3 23 43 56
  5. Association analysis of 15 polymorphisms within 10 candidate genes for antisocial behavioural traits. (PMID: 17728669) Prichard ZM … Easteal S (Psychiatric genetics 2007) 3 23 43 56

Products for LMX1B Gene

  • Boster Bio Antibodies for LMX1B
  • Boster Bio ELISA Kits for LMX1B

Sources for LMX1B Gene