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FLRT2 fibronectin leucine rich transmembrane protein 2 [ Homo sapiens (human) ]

Gene ID: 23768, updated on 2-Nov-2024

Summary

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Official Symbol
FLRT2provided by HGNC
Official Full Name
fibronectin leucine rich transmembrane protein 2provided by HGNC
Primary source
HGNC:HGNC:3761
See related
Ensembl:ENSG00000185070 MIM:604807; AllianceGenome:HGNC:3761
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary
This gene encodes a member of the fibronectin leucine rich transmembrane (FLRT) family of cell adhesion molecules, which regulate early embryonic vascular and neural development. The encoded type I transmembrane protein has an extracellular region consisting of an N-terminal leucine-rich repeat domain and a type 3 fibronectin domain, followed by a transmembrane domain and a short C-terminal cytoplasmic tail domain. It functions as both a homophilic cell adhesion molecule and a heterophilic chemorepellent through its interaction with members of the uncoordinated-5 receptor family. Proteolytic removal of the extracellular region controls the migration of neurons in the developing cortex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]
Expression
Ubiquitous expression in ovary (RPKM 6.8), brain (RPKM 2.7) and 21 other tissues See more
Orthologs
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Genomic context

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See FLRT2 in Genome Data Viewer
Location:
14q31.3
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (85530144..85654428)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (79742250..79868256)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (85996488..86120772)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 2329 Neighboring gene long intergenic non-protein coding RNA 911 Neighboring gene FLRT2 antisense RNA 1 Neighboring gene NANOG hESC enhancer GRCh37_chr14:86035212-86035730 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:86041781-86042407 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38044 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38047 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38246 Neighboring gene NANOG hESC enhancer GRCh37_chr14:86342091-86342659 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8832 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8831 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38309 Neighboring gene long intergenic non-protein coding RNA 2328 Neighboring gene long intergenic non-protein coding RNA 2316 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38386 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:86545921-86546560 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:86546561-86547199 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:86567507-86568008 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:86582175-86582676 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38415 Neighboring gene Sharpr-MPRA regulatory region 9105 Neighboring gene long intergenic non-protein coding RNA 2309

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. FLRT2 suppresses bladder cancer progression through inducing ferroptosis. Jiang P, et al. J Cell Mol Med, 2024 Mar. PMID 37480224, Free PMC Article
  2. A novel autoantibody against fibronectin leucine-rich transmembrane protein 2 expressed on the endothelial cell surface identified by retroviral vector system in systemic lupus erythematosus. Shirai T, et al. Arthritis Res Ther, 2012 Jul 2. PMID 22747982, Free PMC Article
  3. Epigenetically regulated Fibronectin leucine rich transmembrane protein 2 (FLRT2) shows tumor suppressor activity in breast cancer cells. Bae H, et al. Sci Rep, 2017 Mar 21. PMID 28325946, Free PMC Article
  4. Methylation profiling identified novel differentially methylated markers including OPCML and FLRT2 in prostate cancer. Wu Y, et al. Epigenetics, 2016 Apr 2. PMID 26890304, Free PMC Article
  5. FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway. Hwang HJ, et al. JCI Insight, 2024 Apr 8. PMID 38587072, Free PMC Article

See all (34) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. FLRT2 suppresses bladder cancer progression through inducing ferroptosis.
    Title: FLRT2 suppresses bladder cancer progression through inducing ferroptosis.
  2. FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway.
    Title: FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway.
  3. Taken together, these results provide insights into the role of FLRT2 as a novel tumor suppressor in the breast, which is inactivated by hypermethylation during tumor development.
    Title: Epigenetically regulated Fibronectin leucine rich transmembrane protein 2 (FLRT2) shows tumor suppressor activity in breast cancer cells.
  4. OPCML and FLRT2 were further validated in an independent cohort consisting of 20 low-Gleason and 33 high-Gleason tissues. We then compared patients with biochemical recurrence (n=70) vs. those without (n=86) in a third cohort, and they showed no difference in methylation at these DMR loci
    Title: Methylation profiling identified novel differentially methylated markers including OPCML and FLRT2 in prostate cancer.
  5. The membrane protein, FLRT2, was identified as a novel autoantigen in systemic lupus erythematosus patients.
    Title: A novel autoantibody against fibronectin leucine-rich transmembrane protein 2 expressed on the endothelial cell surface identified by retroviral vector system in systemic lupus erythematosus.
  6. PCMC expression of ADAM29, FLRT2, and SLC18A3 could be assessed as part of a routine screen to help identify individuals at risk of severe Obstructive sleep apnea in Asian populations
    Title: Gene expression profiles in peripheral blood mononuclear cells of Asian obstructive sleep apnea patients.
  7. Observational study of gene-disease association. (HuGE Navigator)
    Title: Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study identifies loci affecting blood copper, selenium and zinc.
EBI GWAS Catalog
Genome-wide association study of age at menarche in African-American women.
EBI GWAS Catalog
Genome-wide association study of lung function decline in adults with and without asthma.
EBI GWAS Catalog
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ51243, KIAA0405

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables chemorepellent activity IEA
Inferred from Electronic Annotation
more info
  
enables fibroblast growth factor receptor binding IEA
Inferred from Electronic Annotation
more info
  
enables protein-macromolecule adaptor activity NAS
Non-traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in axon guidance IEA
Inferred from Electronic Annotation
more info
  
involved_in basement membrane organization ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in biological_process ND
No biological Data available
more info
  
involved_in cell adhesion involved in heart morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in fibroblast growth factor receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in heart morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative chemotaxis IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of synapse assembly IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of neuron migration IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of postsynapse assembly IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cell-cell junction ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in endoplasmic reticulum membrane IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular matrix NAS
Non-traceable Author Statement
more info
 PubMed 
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in focal adhesion HDA PubMed 
colocalizes_with focal adhesion ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
located_in neuron projection IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in plasma membrane NAS
Non-traceable Author Statement
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in postsynaptic membrane IEA
Inferred from Electronic Annotation
more info
  
located_in presynaptic membrane IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
leucine-rich repeat transmembrane protein FLRT2
Names
fibronectin-like domain-containing leucine-rich transmembrane protein 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001346143.2 → NP_001333072.1  leucine-rich repeat transmembrane protein FLRT2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2, 3, 4, and 5 encode the same protein.
    Source sequence(s)
    AL049775, AL132641
    Consensus CDS
    CCDS9877.1
    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155
    UniProtKB/TrEMBL
    B3KPR2
    Related
    ENSP00000507815.1, ENST00000683129.1
    Conserved Domains (7) summary
    TIGR00864
    Location:282 → 359
    PCC; polycystin cation channel protein
    smart00013
    Location:35 → 66
    LRRNT; Leucine rich repeat N-terminal domain
    sd00031
    Location:65 → 86
    LRR_1; leucine-rich repeat [structural motif]
    sd00033
    Location:90 → 110
    LRR_RI; leucine-rich repeat [structural motif]
    pfam00041
    Location:426 → 494
    fn3; Fibronectin type III domain
    pfam13855
    Location:252 → 311
    LRR_8; Leucine rich repeat
    cl26018
    Location:54 → 265
    NEL; C-terminal novel E3 ligase, LRR-interacting

  2. NM_001346144.2 → NP_001333073.1  leucine-rich repeat transmembrane protein FLRT2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate exon in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein.
    Source sequence(s)
    AL049775, AL132641
    Consensus CDS
    CCDS9877.1
    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155
    UniProtKB/TrEMBL
    B3KPR2
    Related
    ENSP00000451050.1, ENST00000554746.1
    Conserved Domains (7) summary
    TIGR00864
    Location:282 → 359
    PCC; polycystin cation channel protein
    smart00013
    Location:35 → 66
    LRRNT; Leucine rich repeat N-terminal domain
    sd00031
    Location:65 → 86
    LRR_1; leucine-rich repeat [structural motif]
    sd00033
    Location:90 → 110
    LRR_RI; leucine-rich repeat [structural motif]
    pfam00041
    Location:426 → 494
    fn3; Fibronectin type III domain
    pfam13855
    Location:252 → 311
    LRR_8; Leucine rich repeat
    cl26018
    Location:54 → 265
    NEL; C-terminal novel E3 ligase, LRR-interacting

  3. NM_001346145.2 → NP_001333074.1  leucine-rich repeat transmembrane protein FLRT2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate exon in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein.
    Source sequence(s)
    AL049775, AL132641
    Consensus CDS
    CCDS9877.1
    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155
    UniProtKB/TrEMBL
    B3KPR2
    Conserved Domains (7) summary
    TIGR00864
    Location:282 → 359
    PCC; polycystin cation channel protein
    smart00013
    Location:35 → 66
    LRRNT; Leucine rich repeat N-terminal domain
    sd00031
    Location:65 → 86
    LRR_1; leucine-rich repeat [structural motif]
    sd00033
    Location:90 → 110
    LRR_RI; leucine-rich repeat [structural motif]
    pfam00041
    Location:426 → 494
    fn3; Fibronectin type III domain
    pfam13855
    Location:252 → 311
    LRR_8; Leucine rich repeat
    cl26018
    Location:54 → 265
    NEL; C-terminal novel E3 ligase, LRR-interacting

  4. NM_001346146.2 → NP_001333075.1  leucine-rich repeat transmembrane protein FLRT2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) uses an alternate exon in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein.
    Source sequence(s)
    AL049775, AL132641
    Consensus CDS
    CCDS9877.1
    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155
    UniProtKB/TrEMBL
    B3KPR2
    Related
    ENSP00000507088.1, ENST00000682132.1
    Conserved Domains (7) summary
    TIGR00864
    Location:282 → 359
    PCC; polycystin cation channel protein
    smart00013
    Location:35 → 66
    LRRNT; Leucine rich repeat N-terminal domain
    sd00031
    Location:65 → 86
    LRR_1; leucine-rich repeat [structural motif]
    sd00033
    Location:90 → 110
    LRR_RI; leucine-rich repeat [structural motif]
    pfam00041
    Location:426 → 494
    fn3; Fibronectin type III domain
    pfam13855
    Location:252 → 311
    LRR_8; Leucine rich repeat
    cl26018
    Location:54 → 265
    NEL; C-terminal novel E3 ligase, LRR-interacting

  5. NM_013231.6 → NP_037363.1  leucine-rich repeat transmembrane protein FLRT2 precursor

    See identical proteins and their annotated locations for NP_037363.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate exon in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein.
    Source sequence(s)
    AL049775, AL132641
    Consensus CDS
    CCDS9877.1
    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155
    UniProtKB/TrEMBL
    B3KPR2
    Related
    ENSP00000332879.4, ENST00000330753.6
    Conserved Domains (7) summary
    TIGR00864
    Location:282 → 359
    PCC; polycystin cation channel protein
    smart00013
    Location:35 → 66
    LRRNT; Leucine rich repeat N-terminal domain
    sd00031
    Location:65 → 86
    LRR_1; leucine-rich repeat [structural motif]
    sd00033
    Location:90 → 110
    LRR_RI; leucine-rich repeat [structural motif]
    pfam00041
    Location:426 → 494
    fn3; Fibronectin type III domain
    pfam13855
    Location:252 → 311
    LRR_8; Leucine rich repeat
    cl26018
    Location:54 → 265
    NEL; C-terminal novel E3 ligase, LRR-interacting

RNA

  1. NR_144385.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) contains the same first exon but uses an alternate 3' exon structure, compared to variant 1 and lacks the coding region found in variant 1. This variant is represented as non-coding because it lacks the entire coding region found in variant 1.
    Source sequence(s)
    AL049775, BX119446

  2. NR_144386.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8) uses an alternate exon structure compared to variant 1 and lacks the coding region found in variant 1. This variant is represented as non-coding because it lacks the entire coding region found in variant 1.
    Source sequence(s)
    AL049775, BX119446

  3. NR_144387.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) uses an alternate exon structure compared to variant 1 and lacks the coding region found in variant 1. This variant is represented as non-coding because it lacks the entire coding region found in variant 1.
    Source sequence(s)
    AL049775, BX119446
    Related
    ENST00000557419.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

    Range
    85530144..85654428
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047431176.1 → XP_047287132.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060938.1 Alternate T2T-CHM13v2.0

    Range
    79742250..79868256
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_060077468.1 → XP_059933451.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155

  2. XM_060077469.1 → XP_059933452.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155

  3. XM_060077472.1 → XP_059933455.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155

  4. XM_060077471.1 → XP_059933454.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155

  5. XM_060077466.1 → XP_059933449.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155

  6. XM_060077470.1 → XP_059933453.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155

  7. XM_047446351.1 → XP_047302307.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155

  8. XM_047446350.1 → XP_047302306.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155

  9. XM_060077467.1 → XP_059933450.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155

  10. XM_060077473.1 → XP_059933456.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155

  11. XM_060077465.1 → XP_059933448.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155

  12. XM_047446352.1 → XP_047302308.1  leucine-rich repeat transmembrane protein FLRT2 isoform X1

    UniProtKB/Swiss-Prot
    A0AV84, B7ZLP3, O43155
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O43155.1 GenPept UniProtKB/Swiss-Prot:O43155

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