Human Gene NIPBL (ENST00000282516.13) from GENCODE V43
  Description: Homo sapiens NIPBL cohesin loading factor (NIPBL), transcript variant A, mRNA. (from RefSeq NM_133433)
RefSeq Summary (NM_133433): 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].
Gencode Transcript: ENST00000282516.13
Gencode Gene: ENSG00000164190.19
Transcript (Including UTRs)
   Position: hg38 chr5:36,876,769-37,066,413 Size: 189,645 Total Exon Count: 47 Strand: +
Coding Region
   Position: hg38 chr5:36,953,697-37,064,892 Size: 111,196 Coding Exon Count: 46 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-02-17 13:02:02

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr5:36,876,769-37,066,413)mRNA (may differ from genome)Protein (2804 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSCGAPEnsemblEntrez GeneExonPrimerGencode

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Nipped-B-like protein; AltName: Full=Delangin; AltName: Full=SCC2 homolog;
FUNCTION: Probably plays a structural role in chromatin. Involved in sister chromatid cohesion, possibly by interacting with the cohesin complex (By similarity).
SUBUNIT: Interacts directly with CBX5 via the PxVxL motif.
SUBCELLULAR LOCATION: Nucleus (By similarity).
TISSUE SPECIFICITY: Widely expressed. Highly expressed in heart, skeletal muscle, fetal and adult liver, fetal and adult kidney. Expressed at intermediates level in thymus, placenta, peripheral leukocyte and small intestine. Weakly or not expressed in brain, colon, spleen and lung.
DEVELOPMENTAL STAGE: In embryos, it is expressed in developing limbs and later in cartilage primordia of the ulna and of various hand bones. Sites of craniofacial expression include the cartilage primordium of the basioccipital and basisphenoid skull bones and elsewhere in the head and face, including a region encompassing the mesenchyme adjacent to the cochlear canal. Also expressed in the spinal column, notochord and surface ectoderm sclerotome and what seem to be migrating myoblasts. Expressed in the developing heart in the atrial and ventricular myocardium and in the ventricular tubeculae but absent in the endocardial cushions. Also expressed in the developing esophagus, trachea and midgut loops, in the bronchi of the lung and in the tubules of the metanephros. Expression in organs and tissues not typically affected in CDL (e.g. the developing trachea, bronchi, esophagus, heart and kidney) may reflect a bias towards underreporting of more subtle aspects of the phenotype or problems that typically present later in life. Expressed in the mesenchyme surrounding the cochlear canal possibly reflecting the hearing impairment commonly found. Weakly or not expressed in embryonic brain.
DOMAIN: Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
DISEASE: Defects in NIPBL are the cause of Cornelia de Lange syndrome type 1 (CDLS1) [MIM:122470]. CDLS is a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. CDLS is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation and various other malformations including gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies.
SIMILARITY: Belongs to the SCC2/Nipped-B family.
SIMILARITY: Contains 5 HEAT repeats.
SEQUENCE CAUTION: Sequence=AAH33847.1; Type=Erroneous initiation; Sequence=BAA77335.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA; Sequence=BAA77349.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA; Sequence=BAC86701.1; Type=Erroneous initiation; Sequence=CAE45790.1; Type=Frameshift; Positions=278;
WEB RESOURCE: Name=GeneReviews; URL="";

-  Primer design for this transcript

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3

-  MalaCards Disease Associations
  MalaCards Gene Search: NIPBL
Diseases sorted by gene-association score: cornelia de lange syndrome 1* (1232), nipbl-related cornelia de lange syndrome* (500), cornelia de lange syndrome* (303), chromosome 5p13 duplication syndrome* (30), global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies (14), sc phocomelia syndrome (8), chromosomal duplication syndrome (8), kbg syndrome (5), blepharitis (5), warsaw breakage syndrome (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 10.70 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 323.95 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -172.70489-0.353 Picture PostScript Text
3' UTR -321.801521-0.212 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011989 - ARM-like
IPR016024 - ARM-type_fold
IPR026003 - Cohesin_HEAT
IPR024986 - Nipped-B_C

Pfam Domains:
PF12765 - HEAT repeat associated with sister chromatid cohesion
PF12830 - Sister chromatid cohesion C-terminus

ModBase Predicted Comparative 3D Structure on Q6KC79
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein SequenceProtein SequenceProtein SequenceProtein Sequence 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003682 chromatin binding
GO:0005515 protein binding
GO:0008022 protein C-terminus binding
GO:0036033 mediator complex binding
GO:0042826 histone deacetylase binding
GO:0047485 protein N-terminus binding
GO:0070087 chromo shadow domain binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001656 metanephros development
GO:0003007 heart morphogenesis
GO:0003151 outflow tract morphogenesis
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006974 cellular response to DNA damage stimulus
GO:0007049 cell cycle
GO:0007064 mitotic sister chromatid cohesion
GO:0007275 multicellular organism development
GO:0007420 brain development
GO:0007507 heart development
GO:0007605 sensory perception of sound
GO:0010468 regulation of gene expression
GO:0019827 stem cell population maintenance
GO:0031065 positive regulation of histone deacetylation
GO:0034088 maintenance of mitotic sister chromatid cohesion
GO:0034613 cellular protein localization
GO:0035115 embryonic forelimb morphogenesis
GO:0035136 forelimb morphogenesis
GO:0035261 external genitalia morphogenesis
GO:0040018 positive regulation of multicellular organism growth
GO:0042471 ear morphogenesis
GO:0042634 regulation of hair cycle
GO:0045444 fat cell differentiation
GO:0045778 positive regulation of ossification
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0045995 regulation of embryonic development
GO:0048557 embryonic digestive tract morphogenesis
GO:0048589 developmental growth
GO:0048592 eye morphogenesis
GO:0048638 regulation of developmental growth
GO:0048701 embryonic cranial skeleton morphogenesis
GO:0048703 embryonic viscerocranium morphogenesis
GO:0050890 cognition
GO:0060325 face morphogenesis
GO:0061010 gall bladder development
GO:0061038 uterus morphogenesis
GO:0071481 cellular response to X-ray
GO:0071921 cohesin loading
GO:2001224 positive regulation of neuron migration

Cellular Component:
GO:0000785 chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0032039 integrator complex
GO:0032116 SMC loading complex
GO:0070062 extracellular exosome
GO:0090694 Scc2-Scc4 cohesin loading complex

-  Descriptions from all associated GenBank mRNAs
  KJ897561 - Synthetic construct Homo sapiens clone ccsbBroadEn_06955 SLC1A3 gene, encodes complete protein.
AJ640137 - Homo sapiens mRNA for delangin (NIPBL gene), variant B.
AJ627032 - Homo sapiens mRNA for delangin (NIPBL gene), variant A.
BC146821 - Homo sapiens Nipped-B homolog (Drosophila), mRNA (cDNA clone IMAGE:8860431), partial cds.
BX640644 - Homo sapiens mRNA; cDNA DKFZp686J10142 (from clone DKFZp686J10142).
BC131490 - Homo sapiens Nipped-B homolog (Drosophila), mRNA (cDNA clone IMAGE:40071307), complete cds.
AK290347 - Homo sapiens cDNA FLJ75519 partial cds.
BX538178 - Homo sapiens mRNA; cDNA DKFZp686O04173 (from clone DKFZp686O04173).
BX538177 - Homo sapiens mRNA; cDNA DKFZp686N05173 (from clone DKFZp686N05173).
AY726600 - Homo sapiens clone MO-31 mRNA sequence.
AK126804 - Homo sapiens cDNA FLJ44854 fis, clone BRACE3052410, highly similar to Homo sapiens IDN3 protein (IDN3).
BC032711 - Homo sapiens Nipped-B homolog (Drosophila), mRNA (cDNA clone IMAGE:5496103), with apparent retained intron.
KJ807789 - UNVERIFIED: Homo sapiens clone Del10 Nipped-B-like (NIPBL) mRNA, partial sequence.
AB019602 - Homo sapiens IDN3-B mRNA, complete cds.
AB019494 - Homo sapiens IDN3 mRNA, partial cds.
JD504803 - Sequence 485827 from Patent EP1572962.
JD532520 - Sequence 513544 from Patent EP1572962.
JD071547 - Sequence 52571 from Patent EP1572962.
JD230972 - Sequence 211996 from Patent EP1572962.
KJ807790 - UNVERIFIED: Homo sapiens clone Del12 Nipped-B-like (NIPBL) mRNA, partial sequence.
KJ807791 - UNVERIFIED: Homo sapiens clone Del33_34 Nipped-B-like (NIPBL) mRNA, partial sequence.
AK023416 - Homo sapiens cDNA FLJ13354 fis, clone PLACE1000004, highly similar to Homo sapiens IDN3-B mRNA.
AK022659 - Homo sapiens cDNA FLJ12597 fis, clone NT2RM4001371, highly similar to Homo sapiens IDN3 mRNA.
AK002065 - Homo sapiens cDNA FLJ11203 fis, clone PLACE1007791, highly similar to Homo sapiens IDN3-B mRNA.
BC063859 - Homo sapiens cDNA clone IMAGE:6186421, with apparent retained intron.
BC033847 - Homo sapiens Nipped-B homolog (Drosophila), mRNA (cDNA clone IMAGE:4498111), complete cds.
AL137726 - Homo sapiens mRNA; cDNA DKFZp434L1319 (from clone DKFZp434L1319).
KJ807792 - UNVERIFIED: Homo sapiens clone Del45 Nipped-B-like (NIPBL) mRNA, partial sequence.
KJ906103 - Synthetic construct Homo sapiens clone ccsbBroadEn_15773 NIPBL gene, encodes complete protein.
AK023710 - Homo sapiens cDNA FLJ13648 fis, clone PLACE1011340, weakly similar to Homo sapiens IDN3-B mRNA.
JD341330 - Sequence 322354 from Patent EP1572962.
JD425207 - Sequence 406231 from Patent EP1572962.
JD186770 - Sequence 167794 from Patent EP1572962.
JD358328 - Sequence 339352 from Patent EP1572962.
JD072791 - Sequence 53815 from Patent EP1572962.
JD467799 - Sequence 448823 from Patent EP1572962.
JD042313 - Sequence 23337 from Patent EP1572962.
JD562318 - Sequence 543342 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q6KC79 (Reactome details) participates in the following event(s):

R-HSA-2470935 Cohesin binding to decondensed chromatin is facilitated by NIPBL:MAU2
R-HSA-2470946 Cohesin Loading onto Chromatin
R-HSA-68884 Mitotic Telophase/Cytokinesis
R-HSA-68886 M Phase
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-1640170 Cell Cycle

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000282516.1, ENST00000282516.10, ENST00000282516.11, ENST00000282516.12, ENST00000282516.2, ENST00000282516.3, ENST00000282516.4, ENST00000282516.5, ENST00000282516.6, ENST00000282516.7, ENST00000282516.8, ENST00000282516.9, IDN3, NIPBL_HUMAN, NM_133433, Q6KC79, Q6KCD6, Q6N080, Q6ZT92, Q7Z2E6, Q8N4M5, Q9Y6Y3, Q9Y6Y4, uc003jkl.1, uc003jkl.2, uc003jkl.3, uc003jkl.4, uc003jkl.5, uc003jkl.6
UCSC ID: ENST00000282516.13
RefSeq Accession: NM_133433
Protein: Q6KC79 (aka NIPBL_HUMAN or NPBL_HUMAN)
CCDS: CCDS3920.1, CCDS47198.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene NIPBL:
cdh-ov (Congenital Diaphragmatic Hernia Overview)
cdls (Cornelia de Lange Syndrome)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.