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    NEBL nebulette [ Homo sapiens (human) ]

    Gene ID: 10529, updated on 3-Nov-2024

    Summary

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    Official Symbol
    NEBLprovided by HGNC
    Official Full Name
    nebuletteprovided by HGNC
    Primary source
    HGNC:HGNC:16932
    See related
    Ensembl:ENSG00000078114 MIM:605491; AllianceGenome:HGNC:16932
    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
    Also known as
    LASP2; LNEBL; C10orf113; bA165O3.1
    Summary
    This gene encodes a nebulin like protein that is abundantly expressed in cardiac muscle. The encoded protein binds actin and interacts with thin filaments and Z-line associated proteins in striated muscle. This protein may be involved in cardiac myofibril assembly. A shorter isoform of this protein termed LIM nebulette is expressed in non-muscle cells and may function as a component of focal adhesion complexes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
    Expression
    Biased expression in heart (RPKM 103.7), thyroid (RPKM 26.9) and 7 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NEBL in Genome Data Viewer
    Location:
    10p12.31
    Exon count:
    41
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (20779973..21293050, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (20798520..21311782, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (21068902..21581979, complement)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105376442 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:20885982-20886482 Neighboring gene microRNA 4675 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr10:21045700-21046232 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:21046233-21046763 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:21105746-21106945 Neighboring gene uncharacterized LOC102725112 Neighboring gene MT-ND1 pseudogene 21 Neighboring gene Sharpr-MPRA regulatory region 670 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_11562 Neighboring gene uncharacterized LOC124902389 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3119 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:21322529-21322705 Neighboring gene eukaryotic translation initiation factor 4B pseudogene 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:21373491-21373644 Neighboring gene Sharpr-MPRA regulatory region 12489 Neighboring gene NANOG hESC enhancer GRCh37_chr10:21448091-21448641 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:21449895-21450799 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:21450800-21451703 Neighboring gene nucleophosmin 1 pseudogene 30 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:21462498-21463388 Neighboring gene Sharpr-MPRA regulatory region 12641 Neighboring gene NEBL antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3120 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:21570748-21571426 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr10:21571427-21572103 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:21574449-21575208 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:21575969-21576728 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:21581467-21582666 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:21585759-21586559 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3121 Neighboring gene leucine zipper protein 4 pseudogene 1 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr10:21598312-21598930 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:21625535-21626086 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:21645067-21645566 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:21651599-21652196 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:21652197-21652792 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:21661731-21662232 Neighboring gene RNA, U6 small nuclear 15, pseudogene Neighboring gene long intergenic non-protein coding RNA 2643

    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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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Downregulation of NEBL promotes migration and invasion of clear cell renal cell carcinoma by inducing epithelial-mesenchymal transition.
      Title: Downregulation of NEBL promotes migration and invasion of clear cell renal cell carcinoma by inducing epithelial-mesenchymal transition.
    2. LASP2 inhibits trophoblast cell migration and invasion in preeclampsia through inactivation of the Wnt/beta-catenin signaling pathway.
      Title: LASP2 inhibits trophoblast cell migration and invasion in preeclampsia through inactivation of the Wnt/β-catenin signaling pathway.
    3. LASP2 functions as a potential prognostic factor and therapeutic target in nasopharyngeal carcinoma.
      Title: LASP2 functions as a potential prognostic factor and therapeutic target in nasopharyngeal carcinoma.
    4. LASP2 is downregulated in human liver cancer and contributes to hepatoblastoma cell malignant phenotypes through MAPK/ERK pathway.
      Title: LASP2 is downregulated in human liver cancer and contributes to hepatoblastoma cell malignant phenotypes through MAPK/ERK pathway.
    5. Knockdown of LASP2 inhibits the proliferation, migration, and invasion of cervical cancer cells.
      Title: Knockdown of LASP2 inhibits the proliferation, migration, and invasion of cervical cancer cells.
    6. Upregulation of LASP2 inhibits pancreatic cancer cell migration and invasion through suppressing TGF-beta-induced EMT.
      Title: Upregulation of LASP2 inhibits pancreatic cancer cell migration and invasion through suppressing TGF-β-induced EMT.
    7. Survival analysis suggested that overexpressed NEBL in patients with colorectal cancer was associated with a positive prognosis for overall survival.
      Title: Profiles of differentially expressed genes and overexpression of NEBL indicates a positive prognosis in patients with colorectal cancer.
    8. LASP2 may play a significant role in suppressing CRC progression and provided a novel biomarker for CRC therapy
      Title: LASP2 suppresses colorectal cancer progression through JNK/p38 MAPK pathway meditated epithelial-mesenchymal transition.
    9. The levels of phosphorylated FAK (Tyr397 and Tyr925) were increased after overexpressing Lasp2 and were downregulated by transfecting Lasp2-siRNA.
      Title: Lasp2 enhances tumor invasion via facilitating phosphorylation of FAK and predicts poor overall survival of non-small cell lung cancer patients.
    10. predisposition to multibacillary leprosy in Vietnam is associated with CUBN and NEBL common variants in the chromosome 10p13 linkage region
      Title: CUBN and NEBL common variants in the chromosome 10p13 linkage region are associated with multibacillary leprosy in Vietnam.
    Submit: New GeneRIF Correction See all GeneRIFs (20)

    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

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated 2011-12-21)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated 2011-12-21)

    ClinGen Genome Curation Page

    EBI GWAS Catalog

    Description
    A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity.
    EBI GWAS Catalog
    A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.
    EBI GWAS Catalog
    GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer.
    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

    • FLJ53769, MGC119746, MGC119747, MGC176421

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables actin filament binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables actin filament binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cytoskeletal protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cytoskeletal protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables filamin binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables structural constituent of muscle NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables tropomyosin binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cardiac muscle thin filament assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cardiac muscle thin filament assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in I band NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    is_active_in Z disc IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in Z disc IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular exosome HDA PubMed 
    located_in stress fiber IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    nebulette
    Names
    LIM and SH3 protein 2
    LIM-nebulette
    actin-binding Z-disk protein

    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.

    Genomic

    1. NG_017092.1 RefSeqGene

      Range
      5001..399215
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_411

    mRNA and Protein(s)

    1. NM_001173484.2 → NP_001166955.1  nebulette isoform 3

      See identical proteins and their annotated locations for NP_001166955.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' and 3' UTR and has multiple coding region differences, compared to variant 1. These differences cause translation initiation at an alternate start codon and result in a frameshift. The encoded isoform (3) is shorter and has distinct N- and C-termini, compared to isoform 1.
      Source sequence(s)
      AB209311, BC144201, BM973051, DT220372
      UniProtKB/Swiss-Prot
      O76041
      UniProtKB/TrEMBL
      Q59FZ8
      Conserved Domains (2) summary
      smart00227
      Location:98 → 128
      NEBU; The Nebulin repeat is present also in Las1
      cd09447
      Location:5 → 57
      LIM_LASP; The LIM domain of LIM and SH3 Protein (LASP)

    2. NM_001377322.1 → NP_001364251.1  nebulette isoform 4

      Status: REVIEWED

      Source sequence(s)
      AL157398, AL359175, AL731547
      Conserved Domains (4) summary
      smart00227
      Location:98 → 128
      NEBU; The Nebulin repeat is present also in Las1
      cd09447
      Location:5 → 57
      LIM_LASP; The LIM domain of LIM and SH3 Protein (LASP)
      cd11935
      Location:244 → 301
      SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
      pfam00880
      Location:67 → 94
      Nebulin; Nebulin repeat

    3. NM_001377323.1 → NP_001364252.1  nebulette isoform 5

      Status: REVIEWED

      Source sequence(s)
      AL157398, AL359175, AL731547
      UniProtKB/TrEMBL
      Q8N8M3
      Conserved Domains (4) summary
      smart00227
      Location:82 → 112
      NEBU; The Nebulin repeat is present also in Las1
      cd11935
      Location:197 → 254
      SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
      pfam00880
      Location:51 → 78
      Nebulin; Nebulin repeat
      cl02475
      Location:8 → 41
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

    4. NM_001377324.1 → NP_001364253.1  nebulette isoform 6

      Status: REVIEWED

      Source sequence(s)
      AL157398, AL359175, AL731547
      UniProtKB/TrEMBL
      Q8N8M3
      Conserved Domains (3) summary
      smart00227
      Location:79 → 109
      NEBU; The Nebulin repeat is present also in Las1
      cd11935
      Location:194 → 251
      SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
      cl02475
      Location:5 → 38
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

    5. NM_001377325.1 → NP_001364254.1  nebulette isoform 7

      Status: REVIEWED

      Source sequence(s)
      AL157398, AL359175, AL731547
      UniProtKB/TrEMBL
      Q8N8M3
      Conserved Domains (4) summary
      smart00227
      Location:76 → 106
      NEBU; The Nebulin repeat is present also in Las1
      cd11935
      Location:191 → 248
      SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
      pfam00880
      Location:45 → 72
      Nebulin; Nebulin repeat
      cl02475
      Location:2 → 35
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

    6. NM_001377326.1 → NP_001364255.1  nebulette isoform 8

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8), as well as variants 9 and 10, encodes isoform 8.
      Source sequence(s)
      AL157398, AL359175, AL731547
      UniProtKB/TrEMBL
      Q8N8M3
      Conserved Domains (4) summary
      smart00227
      Location:62 → 92
      NEBU; The Nebulin repeat is present also in Las1
      cl02475
      Location:1 → 21
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers
      pfam00880
      Location:31 → 58
      Nebulin; Nebulin repeat
      cl17036
      Location:177 → 234
      SH3; Src Homology 3 domain superfamily

    7. NM_001377327.1 → NP_001364256.1  nebulette isoform 8

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9), as well as variants 8 and 10, encodes isoform 8.
      Source sequence(s)
      AL157398, AL359175, AL731547
      UniProtKB/TrEMBL
      Q8N8M3
      Related
      ENST00000675702.1
      Conserved Domains (4) summary
      smart00227
      Location:62 → 92
      NEBU; The Nebulin repeat is present also in Las1
      cl02475
      Location:1 → 21
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers
      pfam00880
      Location:31 → 58
      Nebulin; Nebulin repeat
      cl17036
      Location:177 → 234
      SH3; Src Homology 3 domain superfamily

    8. NM_001377328.1 → NP_001364257.1  nebulette isoform 8

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10), as well as variants 8 and 9, encodes isoform 8.
      Source sequence(s)
      AL157398, AL359175, AL731547
      UniProtKB/TrEMBL
      Q8N8M3
      Related
      ENST00000675700.1
      Conserved Domains (4) summary
      smart00227
      Location:62 → 92
      NEBU; The Nebulin repeat is present also in Las1
      cl02475
      Location:1 → 21
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers
      pfam00880
      Location:31 → 58
      Nebulin; Nebulin repeat
      cl17036
      Location:177 → 234
      SH3; Src Homology 3 domain superfamily

    9. NM_006393.3 → NP_006384.1  nebulette isoform 1

      See identical proteins and their annotated locations for NP_006384.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1). This isoform (1) is also known as the sarcomeric isoform.
      Source sequence(s)
      AL157398
      Consensus CDS
      CCDS7134.1
      UniProtKB/Swiss-Prot
      B0YJ45, B9EIM9, E9PRX7, O76041, Q2TBD0, Q5VZT2, Q70I54, Q9UIC4
      UniProtKB/TrEMBL
      B0YJ47
      Related
      ENSP00000366326.4, ENST00000377122.9
      Conserved Domains (3) summary
      smart00227
      Location:762 → 791
      NEBU; The Nebulin repeat is present also in Las1
      cd11935
      Location:957 → 1014
      SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
      cl26511
      Location:294 → 712
      Neuromodulin_N; Gap junction protein N-terminal region

    10. NM_213569.2 → NP_998734.1  nebulette isoform 2

      See identical proteins and their annotated locations for NP_998734.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has multiple differences, compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation at an alternate start codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct N-terminus compared to isoform 1. This isoform is referred to as LIM-nebulette or the non-muscle isoform.
      Source sequence(s)
      AB209311, AJ580772, BI522541, BM973051, CR744526
      Consensus CDS
      CCDS7133.1
      UniProtKB/TrEMBL
      Q8N8M3
      Related
      ENSP00000393896.2, ENST00000417816.2
      Conserved Domains (4) summary
      smart00227
      Location:98 → 128
      NEBU; The Nebulin repeat is present also in Las1
      cd09447
      Location:5 → 57
      LIM_LASP; The LIM domain of LIM and SH3 Protein (LASP)
      cd11935
      Location:213 → 270
      SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
      pfam00880
      Location:67 → 94
      Nebulin; Nebulin repeat

    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_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      20779973..21293050 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047424444.1 → XP_047280400.1  nebulette isoform X4

    2. XM_047424443.1 → XP_047280399.1  nebulette isoform X1

    3. XM_011519291.3 → XP_011517593.1  nebulette isoform X1

      See identical proteins and their annotated locations for XP_011517593.1

      UniProtKB/TrEMBL
      B0YJ47
      Conserved Domains (3) summary
      smart00227
      Location:587 → 616
      NEBU; The Nebulin repeat is present also in Las1
      cd11935
      Location:941 → 998
      SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
      pfam00880
      Location:307 → 331
      Nebulin; Nebulin repeat

    4. XM_005252342.6 → XP_005252399.1  nebulette isoform X2

      UniProtKB/TrEMBL
      B0YJ47
      Conserved Domains (3) summary
      smart00227
      Location:569 → 598
      NEBU; The Nebulin repeat is present also in Las1
      cd11935
      Location:923 → 980
      SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
      pfam00880
      Location:289 → 313
      Nebulin; Nebulin repeat

    5. XM_005252343.6 → XP_005252400.1  nebulette isoform X3

      See identical proteins and their annotated locations for XP_005252400.1

      UniProtKB/TrEMBL
      B0YJ47
      Conserved Domains (3) summary
      smart00227
      Location:603 → 632
      NEBU; The Nebulin repeat is present also in Las1
      cd11935
      Location:876 → 933
      SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
      pfam00880
      Location:323 → 347
      Nebulin; Nebulin repeat

    RNA

    1. XR_001746995.3 RNA Sequence

    2. XR_242691.6 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      20798520..21311782 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054364489.1 → XP_054220464.1  nebulette isoform X4

    2. XM_054364486.1 → XP_054220461.1  nebulette isoform X1

    3. XM_054364485.1 → XP_054220460.1  nebulette isoform X1

    4. XM_054364487.1 → XP_054220462.1  nebulette isoform X2

    5. XM_054364488.1 → XP_054220463.1  nebulette isoform X3

    RNA

    1. XR_008488154.1 RNA Sequence

    2. XR_008488155.1 RNA Sequence

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001010896.2: Suppressed sequence

      Description
      NM_001010896.2: This RefSeq was removed because it is now thought that this gene does not encode a protein.

    2. NM_001177483.1: Suppressed sequence

      Description
      NM_001177483.1: This RefSeq was removed because it is now thought that this gene does not encode a protein.

    3. NM_016365.1: Suppressed sequence

      Description
      NM_016365.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O76041.1 GenPept UniProtKB/Swiss-Prot:O76041

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Other Literature Sources
    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools