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
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

Location:: 5p13.2

Exon count:: 49

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	5	NC_000005.10 (36876769..37066413)
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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Genomic Sequence:

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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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

De novo NIPBL Mutations in Vietnamese Patients with Cornelia de Lange Syndrome.
Title: De novo <i>NIPBL</i> Mutations in Vietnamese Patients with Cornelia de Lange Syndrome.
NIPBL and BRD4 cooperate in transcriptional regulation, which should contribute to explain the recently observed CdLS-like phenotype associated with BRD4 mutations.
Title: The Cornelia de Lange Syndrome-associated factor NIPBL interacts with BRD4 ET domain for transcription control of a common set of genes.
he de novo missense variant c.1507A>G (p. Lys503Glu) of the NIPBL gene probably underlies the severe type Cornelia de Lange syndrome in this patient
Title: [Identification of a novel missense NIPBL variant in a juvenile with severe type of Cornelia de Lange syndrome].
The NIPBL movement among chromosomal loops regulates gene expression through dynamic alterations of genome organization.
Title: Roles of NIPBL in maintenance of genome stability.
these data suggest cohesin-mediated alleviation of Etv6 repression is required for dynamic expression at critical erythroid genes during differentiation and how this may be perturbed in myeloid malignancies.
Title: Cohesin-dependent regulation of gene expression during differentiation is lost in cohesin-mutated myeloid malignancies.
Absolute copy numbers and dynamics of cohesin, CTCF, NIPBL, WAPL and sororin were measured by mass spectrometry, fluorescence-correlation spectroscopy and fluorescence recovery after photobleaching in HeLa cells.
Title: Absolute quantification of cohesin, CTCF and their regulators in human cells.
Single nucleotide alterations located within the conserved splice-donor site of intronic regions of the NIPBL gene can give rise to a premature termination of the translation and cause significant changes in the sequence of mRNA transcripts and NIPBL protein structure and function. The latter underline development of Cornelia de Lange syndrome phenotype.
Title: Molecular characterization of two novel intronic variants of NIPBL gene detected in unrelated Cornelia de Lange syndrome patients.
c.7219C to T and p.D2339Lfs*4 mutations of the NIPBL gene probably account for Cornelia de Lange syndrome
Title: [Analysis of clinical manifestation and genetic mutations in two patients with Cornelia de Lange syndrome].
Here, the authors show that, in human cells, cohesin loading onto chromosomes during early S phase requires the replicative helicase MCM2-7 and the kinase DDK. Cohesin and its loader SCC2/4 (NIPBL/MAU2 in humans) associate with DDK and phosphorylated MCM2-7.
Title: MCM2-7-dependent cohesin loading during S phase promotes sister-chromatid cohesion.
BRD4 and NIPBL displayed correlated binding at super-enhancers and appeared to co-regulate developmental gene expression.
Title: BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange-like syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (62)

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	Compare labs
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. GeneReviews: 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

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

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: 310 organisms have orthologs with human gene NIPBL
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
promoter-specific chromatin binding	ISS Inferred from Sequence or Structural Similarity 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
digestive tract development	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 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 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
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
cytosol	IDA Inferred from Direct Assay more info
extracellular exosome	HDA more info	PubMed
integrator complex	ISS Inferred from Sequence or Structural Similarity more info
intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
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_006987.2 RefSeqGene

Range

4887..194531

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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]
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

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: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p13 Primary Assembly

Range

36876769..37066413

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

Related

ENSP00000499536.1, ENST00000652901.1
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]