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    NIPBL NIPBL cohesin loading factor [ Homo sapiens (human) ]

    Gene ID: 25836, updated on 3-Nov-2024

    Summary

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    Official Symbol
    NIPBLprovided by HGNC
    Official Full Name
    NIPBL cohesin loading factorprovided by HGNC
    Primary source
    HGNC:HGNC:28862
    See related
    Ensembl:ENSG00000164190 MIM:608667; AllianceGenome:HGNC:28862
    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
    CDLS; IDN3; Scc2; CDLS1; IDN3-B
    Summary
    This gene encodes the homolog of the Drosophila melanogaster Nipped-B gene product and fungal Scc2-type sister chromatid cohesion proteins. The Drosophila protein facilitates enhancer-promoter communication of remote enhancers and plays a role in developmental regulation. It is also homologous to a family of chromosomal adherins with broad roles in sister chromatid cohesion, chromosome condensation, and DNA repair. The human protein has a bipartite nuclear targeting sequence and a putative HEAT repeat. Condensins, cohesins and other complexes with chromosome-related functions also contain HEAT repeats. Mutations in this gene result in Cornelia de Lange syndrome, a disorder characterized by dysmorphic facial features, growth delay, limb reduction defects, and cognitive disability. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in thyroid (RPKM 7.3), bone marrow (RPKM 7.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NIPBL in Genome Data Viewer
    Location:
    5p13.2
    Exon count:
    48
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (36876769..37066413)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (37126599..37316247)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (36876871..37066515)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene solute carrier family 1 member 3 Neighboring gene SLC1A3 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22480 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15973 Neighboring gene Sharpr-MPRA regulatory region 9536 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22481 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22482 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22483 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15974 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22484 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15975 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15976 Neighboring gene NIPBL divergent transcript Neighboring gene keratin 18 pseudogene 31 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:37013539-37014053 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:37014054-37014567 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:37086387-37087171 Neighboring gene NANOG hESC enhancer GRCh37_chr5:37093777-37094356 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15977 Neighboring gene ciliogenesis and planar polarity effector complex subunit 1 Neighboring gene ribosomal protein S4X pseudogene 6 Neighboring gene RBIS pseudogene 2

    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. Thrombocytopenia and Cornelia de Lange syndrome: Still an enigma? Cavalleri V, et al. Am J Med Genet A, 2016 Jan. PMID 26437745
    2. NIPBL, a cohesion loading factor, is somatically mutated in gastric and colorectal cancers with high microsatellite instability. Kim MS, et al. Dig Dis Sci, 2013 Nov. PMID 23912250
    3. Cohesin mediates DNA loop extrusion by a "swing and clamp" mechanism. Bauer BW, et al. Cell, 2021 Oct 14. PMID 34624221, Free PMC Article
    4. A novel mutation in NIPBL in a case of Cornelia de Lange syndrome confirmed with genetic testing following intrauterine fetal death. [Corrected]. Jones GE, et al. J Clin Pathol, 2014 Mar. PMID 24189319
    5. Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood. Latorre-Pellicer A, et al. Sci Rep, 2021 Jul 29. PMID 34326454, Free PMC Article

    See all (186) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. NIPBL-mediated RAD21 facilitates tumorigenicity by the PI3K pathway in non-small-cell lung cancer.
      Title: NIPBL-mediated RAD21 facilitates tumorigenicity by the PI3K pathway in non-small-cell lung cancer.
    2. Different NIPBL requirements of cohesin-STAG1 and cohesin-STAG2.
      Title: Different NIPBL requirements of cohesin-STAG1 and cohesin-STAG2.
    3. Deep intronic NIPBL de novo mutations and differential diagnoses revealed by whole genome and RNA sequencing in Cornelia de Lange syndrome patients.
      Title: Deep intronic NIPBL de novo mutations and differential diagnoses revealed by whole genome and RNA sequencing in Cornelia de Lange syndrome patients.
    4. uORF-introducing variants in the 5'UTR of the NIPBL gene as a cause of Cornelia de Lange syndrome.
      Title: uORF-introducing variants in the 5'UTR of the NIPBL gene as a cause of Cornelia de Lange syndrome.
    5. A Novel de Novo Variant in 5' UTR of the NIPBL Associated with Cornelia de Lange Syndrome.
      Title: A Novel de Novo Variant in 5' UTR of the NIPBL Associated with Cornelia de Lange Syndrome.
    6. Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion.
      Title: Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion.
    7. Implications of Dosage Deficiencies in CTCF and Cohesin on Genome Organization, Gene Expression, and Human Neurodevelopment.
      Title: Implications of Dosage Deficiencies in CTCF and Cohesin on Genome Organization, Gene Expression, and Human Neurodevelopment.
    8. The glucocorticoid receptor associates with the cohesin loader NIPBL to promote long-range gene regulation.
      Title: The glucocorticoid receptor associates with the cohesin loader NIPBL to promote long-range gene regulation.
    9. Cohesin mediates DNA loop extrusion by a ""swing and clamp"" mechanism.
      Title: Cohesin mediates DNA loop extrusion by a "swing and clamp" mechanism.
    10. MicroRNA-99b inhibits NSCLC cell invasion and migration by directly targeting NIPBL.
      Title: MicroRNA-99b inhibits NSCLC cell invasion and migration by directly targeting NIPBL.
    Submit: New GeneRIF Correction See all GeneRIFs (81)

    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

    Associated conditions

    Description Tests
    Cornelia de Lange syndrome 1
    MedGen: C4551851 OMIM: 122470 GeneReviews: Cornelia de Lange Syndrome
    		not available

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    Little evidence for dosage pathogenicity (Last evaluated 2020-08-26)

    ClinGen Genome Curation PagePubMed
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2020-08-26)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Rev rev HIV-1 Rev interacting protein, Nipped-B homolog (NIPBL), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells. The interaction of Rev with NIPBL is increased by RRE PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ11203, FLJ12597, FLJ13354, FLJ13648, FLJ44854, DKFZp434L1319

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables chromatin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables chromo shadow domain binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables cohesin loader activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables histone deacetylase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables mediator complex binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables promoter-specific chromatin binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transcription corepressor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA damage response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in brain development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in brain development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to X-ray IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in chromatin remodeling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cognition IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in developmental growth IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in digestive tract development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in ear morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in embryonic digestive tract morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in embryonic forelimb morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in embryonic viscerocranium morphogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in establishment of mitotic sister chromatid cohesion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in establishment of protein localization to chromatin IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in external genitalia morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in eye morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in face morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in fat cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in forelimb morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in gallbladder development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in heart morphogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in heart morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in maintenance of mitotic sister chromatid cohesion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in metanephros development NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in mitotic cohesin loading IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mitotic sister chromatid cohesion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mitotic sister chromatid cohesion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitotic sister chromatid segregation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in outflow tract morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of multicellular organism growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of neuron migration ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of ossification IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein localization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of developmental growth IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of embryonic development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of hair cycle IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in replication-born double-strand break repair via sister chromatid exchange IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in sensory perception of sound IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in somatic stem cell population maintenance IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in uterus morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of SMC loading complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of Scc2-Scc4 cohesin loading complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of Scc2-Scc4 cohesin loading complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in chromatin IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    part_of integrator complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    nipped-B-like protein
    Names
    Nipped-B homolog
    SCC2 homolog
    delangin
    sister chromatid cohesion 2 homolog

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_006987.2 RefSeqGene

      Range
      4887..194531
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_015384.5 → NP_056199.2  nipped-B-like protein isoform B

      See identical proteins and their annotated locations for NP_056199.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (B) is alternatively spliced at the 3' end compared to transcript variant A. It encodes an isoform (B) with a shorter, distinct C-terminus, compared to isoform A.
      Source sequence(s)
      AA508213, AJ627032, AJ640137, BQ723324, CN369580
      Consensus CDS
      CCDS47198.1
      UniProtKB/TrEMBL
      Q6IEH8
      Related
      ENSP00000406266.2, ENST00000448238.2
      Conserved Domains (5) summary
      pfam07223
      Location:113 → 307
      DUF1421; Protein of unknown function (DUF1421)
      pfam08648
      Location:1103 → 1160
      DUF1777; Protein of unknown function (DUF1777)
      pfam12765
      Location:1794 → 1835
      Cohesin_HEAT; HEAT repeat associated with sister chromatid cohesion
      pfam12830
      Location:2276 → 2454
      Nipped-B_C; Sister chromatid cohesion C-terminus
      sd00044
      Location:1811 → 1839
      HEAT; HEAT repeat [structural motif]

    2. NM_133433.4 → NP_597677.2  nipped-B-like protein isoform A

      See identical proteins and their annotated locations for NP_597677.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (A) encodes the longer isoform (A).
      Source sequence(s)
      AC008902, AJ627032, CN369580
      Consensus CDS
      CCDS3920.1
      UniProtKB/Swiss-Prot
      Q6KC79, Q6KCD6, Q6N080, Q6ZT92, Q7Z2E6, Q8N4M5, Q9Y6Y3, Q9Y6Y4
      UniProtKB/TrEMBL
      Q6IEH8
      Related
      ENSP00000282516.8, ENST00000282516.13
      Conserved Domains (5) summary
      pfam07223
      Location:113 → 307
      DUF1421; Protein of unknown function (DUF1421)
      pfam08648
      Location:1103 → 1160
      DUF1777; Protein of unknown function (DUF1777)
      pfam12765
      Location:1794 → 1835
      Cohesin_HEAT; HEAT repeat associated with sister chromatid cohesion
      pfam12830
      Location:2276 → 2454
      Nipped-B_C; Sister chromatid cohesion C-terminus
      sd00044
      Location:1811 → 1839
      HEAT; HEAT repeat [structural motif]

    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_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      36876769..37066413
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005248280.4 → XP_005248337.1  nipped-B-like protein isoform X3

      See identical proteins and their annotated locations for XP_005248337.1

      UniProtKB/TrEMBL
      Q6IEH8
      Conserved Domains (5) summary
      pfam07223
      Location:113 → 307
      DUF1421; Protein of unknown function (DUF1421)
      pfam08648
      Location:1103 → 1160
      DUF1777; Protein of unknown function (DUF1777)
      pfam12765
      Location:1794 → 1835
      Cohesin_HEAT; HEAT repeat associated with sister chromatid cohesion
      pfam12830
      Location:2276 → 2454
      Nipped-B_C; Sister chromatid cohesion C-terminus
      sd00044
      Location:1811 → 1839
      HEAT; HEAT repeat [structural motif]

    2. XM_017009329.2 → XP_016864818.1  nipped-B-like protein isoform X4

      UniProtKB/TrEMBL
      A0A590UJS4, Q6IEH8
      Related
      ENSP00000499536.1, ENST00000652901.1

    3. XM_006714467.3 → XP_006714530.1  nipped-B-like protein isoform X1

      UniProtKB/TrEMBL
      Q6IEH8
      Conserved Domains (5) summary
      pfam07223
      Location:113 → 307
      DUF1421; Protein of unknown function (DUF1421)
      pfam08648
      Location:1103 → 1160
      DUF1777; Protein of unknown function (DUF1777)
      pfam12765
      Location:1794 → 1835
      Cohesin_HEAT; HEAT repeat associated with sister chromatid cohesion
      pfam12830
      Location:2276 → 2418
      Nipped-B_C; Sister chromatid cohesion C-terminus
      sd00044
      Location:1811 → 1839
      HEAT; HEAT repeat [structural motif]

    4. XM_006714468.3 → XP_006714531.1  nipped-B-like protein isoform X2

      UniProtKB/TrEMBL
      Q6IEH8
      Conserved Domains (4) summary
      pfam07223
      Location:113 → 307
      DUF1421; Protein of unknown function (DUF1421)
      pfam12765
      Location:1728 → 1769
      Cohesin_HEAT; HEAT repeat associated with sister chromatid cohesion
      pfam12830
      Location:2210 → 2388
      Nipped-B_C; Sister chromatid cohesion C-terminus
      sd00044
      Location:1745 → 1773
      HEAT; HEAT repeat [structural motif]

    5. XM_011514015.2 → XP_011512317.1  nipped-B-like protein isoform X6

      UniProtKB/TrEMBL
      Q6IEH8
      Conserved Domains (5) summary
      pfam07223
      Location:113 → 307
      DUF1421; Protein of unknown function (DUF1421)
      pfam08648
      Location:1103 → 1160
      DUF1777; Protein of unknown function (DUF1777)
      pfam12765
      Location:1794 → 1835
      Cohesin_HEAT; HEAT repeat associated with sister chromatid cohesion
      pfam12830
      Location:2276 → 2418
      Nipped-B_C; Sister chromatid cohesion C-terminus
      sd00044
      Location:1811 → 1839
      HEAT; HEAT repeat [structural motif]

    6. XM_005248282.6 → XP_005248339.3  nipped-B-like protein isoform X5

      UniProtKB/TrEMBL
      Q6IEH8

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      37126599..37316247
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054352329.1 → XP_054208304.1  nipped-B-like protein isoform X3

    2. XM_054352330.1 → XP_054208305.1  nipped-B-like protein isoform X4

      UniProtKB/TrEMBL
      A0A590UJS4

    3. XM_054352327.1 → XP_054208302.1  nipped-B-like protein isoform X1

    4. XM_054352328.1 → XP_054208303.1  nipped-B-like protein isoform X2

    5. XM_054352332.1 → XP_054208307.1  nipped-B-like protein isoform X6

    6. XM_054352331.1 → XP_054208306.1  nipped-B-like protein isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6KC79.2 GenPept UniProtKB/Swiss-Prot:Q6KC79

    Gene LinkOut

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

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