NIPBL NIPBL, cohesin loading factor [Homo sapiens (human)] - Gene

Summary

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; Vega:OTTHUMG00000090795
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

Genomic context

Location:: 5p13.2

Exon count:: 48

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	5	NC_000005.10 (36876759..37065819)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (36876861..37065926)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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 Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Frameshift Mutation in NIPBL gene is associated with Cornelia de Lange Syndrome.
Title: A Novel Frameshift Mutation (c.5387_5388insTT) in <i>NIPBL</i> in Cornelia de Lange Syndrome with Severe Phenotype.
In Chinese patients with Cornelia de Lange syndrome, a heterozygous mutation in exon 20 of the NIPBL gene in proband 2, and a heterozygous mutation in intron 38 of the NIPBL gene in proband 3 were found, and RT-PCR revealed a splicing mutation in exon 38, generating both normal transcript and an aberrant alternatively spliced transcript with exon 38 deletion.
Title: Clinical and genetic study of 20 patients from China with Cornelia de Lange syndrome.
Downregulation of cohesin loading factor NIPBL arrested breast cancer cells in vitro in the G0/G1 phase of the cell cycle and induced apoptosis and autophagy.
Title: Downregulation of Cohesin Loading Factor Nipped-B-Like Protein (NIPBL) Induces Cell Cycle Arrest, Apoptosis, and Autophagy of Breast Cancer Cell Lines.
Using fluorescence recovery after photobleaching (FRAP) and single-molecule tracking in human cells, the authors show that Scc2 binds dynamically to chromatin, principally through an association with cohesin.
Title: Scc2/Nipbl hops between chromosomal cohesin rings after loading.
Authors have identified a novel distal enhancer regulating both NIPBL and NIPBL-AS1.
Title: Regulation of the cohesin-loading factor NIPBL: Role of the lncRNA NIPBL-AS1 and identification of a distal enhancer element.
Nipbl seems to have also additional roles, for instance as transcription factor.This chapter summarizes our current knowledge on kollerin function and the recent studies on the genomic localization of Scc2, highlighting and critically discussing controversial data.
Title: Resolving the Genomic Localization of the Kollerin Cohesin-Loader Complex.
The findings suggest similarities in the behavioral phenotype between those with and without the NIPBL mutation once differences in self help skills are controlled for.
Title: Genotype-phenotype correlations in Cornelia de Lange syndrome: Behavioral characteristics and changes with age.
We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group suggest that a disturbed cohesin function contributes to the phenotype, but differences between these groups may also be explained by other underlying mechanisms such as moonlighting of the cohesin genes.
Title: Phenotypes and genotypes in individuals with SMC1A variants.
NIPBL has evolved a sophisticated response to damaged DNA that is influenced by the form of damage, suggesting a highly dynamic role for NIPBL in maintaining genomic stability.
Title: Independent mechanisms recruit the cohesin loader protein NIPBL to sites of DNA damage.
Study identifies four likely Tourette disorder risk genes with multiple de novo damaging variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1).
Title: De Novo Coding Variants Are Strongly Associated with Tourette Disorder.

Submit: New GeneRIF Correction See all GeneRIFs (49)

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: CN029798 OMIM: 122470 GeneReviews: Cornelia de Lange Syndrome	Compare labs

Copy number response

Description
Copy number response Triplosensitivity Little evidence for dosage pathogenicity (Last evaluated (2011-10-28) ClinGen Genome Curation PagePubMed Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated (2011-10-28) ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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 BioSystems

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Cell Cycle, organism-specific biosystem (from REACTOME)
Cell Cycle, organism-specific biosystem
Cell Cycle
Cell Cycle, Mitotic, organism-specific biosystem (from REACTOME)
Cell Cycle, Mitotic, organism-specific biosystemThe replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried o...
Cohesin Loading onto Chromatin, organism-specific biosystem (from REACTOME)
Cohesin Loading onto Chromatin, organism-specific biosystemIn mitotic telophase, as chromosomes decondense, cohesin complex associated with PDS5 (PDS5A and PDS5B) and WAPAL (WAPL) proteins is loaded onto chromatin (Shintomi and Hirano, 2009, Kueng et al. 200...
M Phase, organism-specific biosystem (from REACTOME)
M Phase, organism-specific biosystemMitosis, or the M phase, involves nuclear division and cytokinesis, where two identical daughter cells are produced. Mitosis involves prophase, prometaphase, metaphase, anaphase, and telophase. Fin...
Mitotic Telophase/Cytokinesis, organism-specific biosystem (from REACTOME)
Mitotic Telophase/Cytokinesis, organism-specific biosystemIn this final phase of mitosis, new membranes are formed around two sets of chromatids and two daughter cells are formed. The chromosomes and the spindle fibers disperse, and the fiber ring around th...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:484101

RH76750 (e-PCR)
- UniSTS:85265

L17705 (e-PCR)
- UniSTS:66091

RH65882 (e-PCR)
- UniSTS:80704

MARC_21845-21846:1025102921:1 (e-PCR)
- UniSTS:268649

SGC44479 (e-PCR)
- UniSTS:34153

D5S1878 (e-PCR)
- UniSTS:64148

WI-18161 (e-PCR)
- UniSTS:32166

RH119355 (e-PCR)
- UniSTS:138922

RH47582 (e-PCR)
- UniSTS:83139

D5S1878 (e-PCR)
- UniSTS:181708

Homology

Homologs of the NIPBL gene: The NIPBL gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 223 organisms have orthologs with human gene NIPBL
The Hierarchical Catalog of Orthologs

Clone Names

FLJ11203, FLJ12597, FLJ13354, FLJ13648, FLJ44854, DKFZp434L1319

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
chromatin binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
chromo shadow domain binding	IPI Inferred from Physical Interaction more info	PubMed
histone deacetylase binding	IPI Inferred from Physical Interaction more info	PubMed
mediator complex binding	IEA Inferred from Electronic Annotation more info
protein C-terminus binding	IPI Inferred from Physical Interaction more info	PubMed
protein N-terminus binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
brain development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
brain development	IMP Inferred from Mutant Phenotype more info	PubMed
cellular protein localization	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to DNA damage stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to X-ray	IMP Inferred from Mutant Phenotype more info	PubMed
cognition	IMP Inferred from Mutant Phenotype more info	PubMed
cohesin loading	IDA Inferred from Direct Assay more info	PubMed
developmental growth	IMP Inferred from Mutant Phenotype more info	PubMed
double-strand break repair	IBA Inferred from Biological aspect of Ancestor more info	PubMed
ear morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
embryonic digestive tract morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
embryonic forelimb morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
embryonic viscerocranium morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
establishment of mitotic sister chromatid cohesion	IBA Inferred from Biological aspect of Ancestor more info	PubMed
establishment of protein localization to chromatin	IBA Inferred from Biological aspect of Ancestor more info	PubMed
external genitalia morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
eye morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
face morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
fat cell differentiation	IEA Inferred from Electronic Annotation more info
forelimb morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
gall bladder development	IMP Inferred from Mutant Phenotype more info	PubMed
heart development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
heart morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
heart morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
maintenance of mitotic sister chromatid cohesion	IMP Inferred from Mutant Phenotype more info	PubMed
metanephros development	NAS Non-traceable Author Statement more info	PubMed
mitotic chromosome condensation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitotic sister chromatid cohesion	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitotic sister chromatid cohesion	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
outflow tract morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of histone deacetylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of mitotic cohesin loading	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of multicellular organism growth	IEA Inferred from Electronic Annotation more info
positive regulation of neuron migration	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of ossification	IEA Inferred from Electronic Annotation more info
rDNA condensation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of developmental growth	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of embryonic development	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of hair cycle	IMP Inferred from Mutant Phenotype more info	PubMed
replication-born double-strand break repair via sister chromatid exchange	IBA Inferred from Biological aspect of Ancestor more info	PubMed
sensory perception of sound	IMP Inferred from Mutant Phenotype more info	PubMed
stem cell population maintenance	IEA Inferred from Electronic Annotation more info
transcriptional activation by promoter-enhancer looping	IBA Inferred from Biological aspect of Ancestor more info	PubMed
uterus morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
SMC loading complex	IDA Inferred from Direct Assay more info	PubMed
Scc2-Scc4 cohesin loading complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Scc2-Scc4 cohesin loading complex	IDA Inferred from Direct Assay more info	PubMed
chromatin	IBA Inferred from Biological aspect of Ancestor more info	PubMed
extracellular exosome	HDA more info	PubMed
integrator complex	ISS Inferred from Sequence or Structural Similarity more info
nuclear chromatin	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nuclear chromosome	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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

NG_006987.1 RefSeqGene

Range

4877..193937

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_015384.4 → 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, OTTHUMP00000221091, ENST00000448238.2, OTTHUMT00000366904

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]
NM_133433.3 → 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)

AJ627032, CN369580

Consensus CDS

CCDS3920.1

UniProtKB/Swiss-Prot

Q6KC79

Related

ENSP00000282516.8, OTTHUMP00000116005, ENST00000282516.12, OTTHUMT00000207582

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: Homo sapiens Annotation Release 109 details...

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p12 Primary Assembly

Range

36876759..37065819

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006714467.2 → 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]
XM_005248280.3 → 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]
XM_006714468.2 → 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]
XM_017009331.1 → XP_016864820.1 nipped-B-like protein isoform X8
XM_017009329.1 → XP_016864818.1 nipped-B-like protein isoform X4
XM_011514015.1 → 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]
XM_005248282.5 → XP_005248339.3 nipped-B-like protein isoform X5
XM_017009330.2 → XP_016864819.1 nipped-B-like protein isoform X7

UniProtKB/Swiss-Prot

Q6KC79

Conserved Domains (4) summary

pfam08648
Location:564 → 621

DUF1777; Protein of unknown function (DUF1777)

pfam12765
Location:1255 → 1296

Cohesin_HEAT; HEAT repeat associated with sister chromatid cohesion

pfam12830
Location:1737 → 1915

Nipped-B_C; Sister chromatid cohesion C-terminus

sd00044
Location:1272 → 1300

HEAT; HEAT repeat [structural motif]