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

Gene ID: 25836, updated on 4-Jun-2023

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
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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_2023_03 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (36876769..37066413)
RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (37126599..37316247)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (36876871..37066515)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene SLC1A3 antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 9536 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 ciliogenesis and planar polarity effector complex subunit 1 Neighboring gene ribosomal protein S4X pseudogene 6

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
  • 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. Deep intronic NIPBL de novo mutations and differential diagnoses revealed by whole genome and RNA sequencing in Cornelia de Lange syndrome patients. Coursimault J, et al. Hum Mutat, 2022 Dec. PMID 35842780
  2. A Novel de Novo Variant in 5' UTR of the NIPBL Associated with Cornelia de Lange Syndrome. Chen Y, et al. Genes (Basel), 2022 Apr 22. PMID 35627125, Free PMC Article
  3. Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion. Panarotto M, et al. Proc Natl Acad Sci U S A, 2022 May 3. PMID 35476527, Free PMC Article
  4. uORF-introducing variants in the 5'UTR of the NIPBL gene as a cause of Cornelia de Lange syndrome. Coursimault J, et al. Hum Mutat, 2022 Sep. PMID 35446447
  5. The glucocorticoid receptor associates with the cohesin loader NIPBL to promote long-range gene regulation. Rinaldi L, et al. Sci Adv, 2022 Apr. PMID 35353576, Free PMC Article

See all (169) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Cohesin mediates DNA loop extrusion by a ""swing and clamp"" mechanism.
    Title: Cohesin mediates DNA loop extrusion by a "swing and clamp" mechanism.
  8. 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.
  9. Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood.
    Title: Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood.
  10. Nipped-B-like Protein Sensitizes Esophageal Squamous Cell Carcinoma Cells to Cisplatin via Upregulation of PUMA.
    Title: Nipped-B-like Protein Sensitizes Esophageal Squamous Cell Carcinoma Cells to Cisplatin via Upregulation of PUMA.
Submit: New GeneRIF Correction See all GeneRIFs (79)

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
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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
 PubMed 
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 
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
 PubMed 
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 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
 PubMed 
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
 PubMed 
involved_in establishment of mitotic sister chromatid cohesion IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in establishment of protein localization to chromatin IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
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
 PubMed 
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 DNA-templated transcription IDA
Inferred from Direct Assay
more info
 PubMed 
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 histone deacetylation IDA
Inferred from Direct Assay
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
 PubMed 
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
 PubMed 
part_of Scc2-Scc4 cohesin loading complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of 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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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/Swiss-Prot
    Q6KC79
    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, Q9Y6Y4
    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_2023_03

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

    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
    Related
    ENSP00000499536.1, ENST00000652901.1

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

    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

    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

    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

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

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