This gene encodes a protein that is involved in the activation of the ubiquitous transcription factor NF-kappaB. This protein is associated with the the histone deacetylase HDAC3 and with the Notch corepressor complex, and it thereby acts as a transcriptional repressor of Notch target genes. It is also required for alphabeta T cell development. A related pseudogene has been ide... See more...

Aliases for NKAP Gene

Aliases for NKAP Gene

  • NFKB Activating Protein 2 3 5
  • NF-Kappa-B-Activating Protein 3 4
  • NF KappaB Activating Protein 2
  • NF-KappaB Activating Protein 3
  • FLJ22626 2
  • MRXSHD 3
  • NKAP 5

External Ids for NKAP Gene

Previous GeneCards Identifiers for NKAP Gene

  • GC0XM117813
  • GC0XM118840
  • GC0XM118943
  • GC0XM119059
  • GC0XM108555
  • GC0XM119927
  • GC0XM119943
  • GC0XM119958
  • GC0XM119967

Summaries for NKAP Gene

Entrez Gene Summary for NKAP Gene

  • This gene encodes a protein that is involved in the activation of the ubiquitous transcription factor NF-kappaB. This protein is associated with the the histone deacetylase HDAC3 and with the Notch corepressor complex, and it thereby acts as a transcriptional repressor of Notch target genes. It is also required for alphabeta T cell development. A related pseudogene has been identified on chromosome X, while a related and intronless retrocopy, which has an intact CDS and may be functional, is located on chromosome 6. [provided by RefSeq, May 2010]

GeneCards Summary for NKAP Gene

NKAP (NFKB Activating Protein) is a Protein Coding gene. Diseases associated with NKAP include Intellectual Developmental Disorder, X-Linked, Syndromic, Hackmann-Di Donato Type and Fryns Syndrome. Among its related pathways are Notch Signaling Pathway (WikiPathways). Gene Ontology (GO) annotations related to this gene include chromatin DNA binding. An important paralog of this gene is NKAPL.

UniProtKB/Swiss-Prot Summary for NKAP Gene

  • Acts as a transcriptional repressor (PubMed:14550261, PubMed:19409814, PubMed:31587868). Plays a role as a transcriptional corepressor of the Notch-mediated signaling required for T-cell development (PubMed:19409814). Also involved in the TNF and IL-1 induced NF-kappa-B activation. Associates with chromatin at the Notch-regulated SKP2 promoter.

Gene Wiki entry for NKAP Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NKAP Gene

Genomics for NKAP Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NKAP Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NKAP on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NKAP

Top Transcription factor binding sites by QIAGEN in the NKAP gene promoter:
  • aMEF-2
  • AP-1
  • ATF-2
  • c-Jun
  • C/EBPbeta
  • GATA-1
  • MEF-2A
  • NRF-2
  • p53
  • SRY

Genomic Locations for NKAP Gene

Latest Assembly
chrX:119,920,672-119,943,751
(GRCh38/hg38)
Size:
23,080 bases
Orientation:
Minus strand

Previous Assembly
chrX:119,054,635-119,077,714
(GRCh37/hg19 by Entrez Gene)
Size:
23,080 bases
Orientation:
Minus strand

chrX:119,059,014-119,077,735
(GRCh37/hg19 by Ensembl)
Size:
18,722 bases
Orientation:
Minus strand

Genomic View for NKAP Gene

Genes around NKAP on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NKAP Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NKAP Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NKAP Gene

Proteins for NKAP Gene

  • Protein details for NKAP Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8N5F7-NKAP_HUMAN
    Recommended name:
    NF-kappa-B-activating protein
    Protein Accession:
    Q8N5F7
    Secondary Accessions:
    • Q6IPW6
    • Q96BQ2
    • Q9H638

    Protein attributes for NKAP Gene

    Size:
    415 amino acids
    Molecular mass:
    47138 Da
    Quaternary structure:
    • Component of the Notch corepressor complex. Interacts with CIR1 and HDAC3.
    SequenceCaution:
    • Sequence=AAH71686.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for NKAP Gene

neXtProt entry for NKAP Gene

Post-translational modifications for NKAP Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NKAP Gene

No data available for DME Specific Peptides for NKAP Gene

Domains & Families for NKAP Gene

Gene Families for NKAP Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for NKAP Gene

InterPro:

Suggested Antigen Peptide Sequences for NKAP Gene

GenScript: Design optimal peptide antigens:
  • NKAP protein (A0PJ73_HUMAN)
  • NF-kappa-B-activating protein (NKAP_HUMAN)
  • NKAP protein (Q05D22_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8N5F7

UniProtKB/Swiss-Prot:

NKAP_HUMAN :
  • Belongs to the NKAP family.
Family:
  • Belongs to the NKAP family.
genes like me logo Genes that share domains with NKAP: view

Function for NKAP Gene

Molecular function for NKAP Gene

UniProtKB/Swiss-Prot Function:
Acts as a transcriptional repressor (PubMed:14550261, PubMed:19409814, PubMed:31587868). Plays a role as a transcriptional corepressor of the Notch-mediated signaling required for T-cell development (PubMed:19409814). Also involved in the TNF and IL-1 induced NF-kappa-B activation. Associates with chromatin at the Notch-regulated SKP2 promoter.

Phenotypes From GWAS Catalog for NKAP Gene

Gene Ontology (GO) - Molecular Function for NKAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003682 chromatin binding IEA,IDA 19409814
GO:0003723 RNA binding HDA 22681889
GO:0005515 protein binding IPI 19409814
genes like me logo Genes that share ontologies with NKAP: view
genes like me logo Genes that share phenotypes with NKAP: view

Human Phenotype Ontology for NKAP Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

miRNA for NKAP Gene

miRTarBase miRNAs that target NKAP

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NKAP

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for NKAP Gene

Localization for NKAP Gene

Subcellular locations from UniProtKB/Swiss-Prot for NKAP Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NKAP gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NKAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm IDA --
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with NKAP: view

Pathways & Interactions for NKAP Gene

PathCards logo

SuperPathways for NKAP Gene

genes like me logo Genes that share pathways with NKAP: view

Pathways by source for NKAP Gene

1 R&D Systems pathway for NKAP Gene

Gene Ontology (GO) - Biological Process for NKAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IMP 31587868
GO:0007219 Notch signaling pathway IEA --
GO:0010468 regulation of gene expression IBA 21873635
GO:0045892 negative regulation of transcription, DNA-templated IDA 19409814
GO:0046638 positive regulation of alpha-beta T cell differentiation IMP 19409814
genes like me logo Genes that share ontologies with NKAP: view

No data available for SIGNOR curated interactions for NKAP Gene

Drugs & Compounds for NKAP Gene

No Compound Related Data Available

Transcripts for NKAP Gene

mRNA/cDNA for NKAP Gene

1 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NKAP

Alternative Splicing Database (ASD) splice patterns (SP) for NKAP Gene

No ASD Table

Relevant External Links for NKAP Gene

GeneLoc Exon Structure for
NKAP

Expression for NKAP Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NKAP Gene

Protein differential expression in normal tissues from HIPED for NKAP Gene

This gene is overexpressed in Adrenal (23.0), Fetal ovary (13.6), Monocytes (10.0), and CD4 Tcells (6.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NKAP Gene



Protein tissue co-expression partners for NKAP Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NKAP

SOURCE GeneReport for Unigene cluster for NKAP Gene:

Hs.522771

Evidence on tissue expression from TISSUES for NKAP Gene

  • Intestine(4.3)
  • Spleen(2.3)
  • Liver(2.1)
  • Nervous system(2.1)
  • Kidney(2)
genes like me logo Genes that share expression patterns with NKAP: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for NKAP Gene

Orthologs for NKAP Gene

This gene was present in the common ancestor of animals.

Orthologs for NKAP Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NKAP 29 30
  • 98.51 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NKAP 29 30
  • 94.75 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NKAP 29 30
  • 91.81 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Nkap 29 16 30
  • 84.1 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Nkap 29
  • 83.13 (n)
Oppossum
(Monodelphis domestica)
Mammalia -- 30
  • 69 (a)
OneToMany
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 62 (a)
OneToMany
Chicken
(Gallus gallus)
Aves NKAP 30
  • 71 (a)
OneToMany
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 61 (a)
OneToMany
African clawed frog
(Xenopus laevis)
Amphibia nuc06-A-prov 29
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia Str.11365 29
Zebrafish
(Danio rerio)
Actinopterygii nkap 30
  • 54 (a)
OneToMany
wufj36d09 29
Fruit Fly
(Drosophila melanogaster)
Insecta CG6066 30
  • 33 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea let-504 30
  • 25 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 42 (a)
OneToMany
Species where no ortholog for NKAP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for NKAP Gene

ENSEMBL:
Gene Tree for NKAP (if available)
TreeFam:
Gene Tree for NKAP (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NKAP: view image
Alliance of Genome Resources:
Additional Orthologs for NKAP

Paralogs for NKAP Gene

Paralogs for NKAP Gene

(1) SIMAP similar genes for NKAP Gene using alignment to 3 proteins:

  • NKAP_HUMAN
  • A0PJ73_HUMAN
  • Q05D22_HUMAN
genes like me logo Genes that share paralogs with NKAP: view

Variants for NKAP Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NKAP Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
rs1603379318 Pathogenic: Intellectual developmental disorder, x-linked, syndromic, Hackmann-Di Donato type 119,925,386(-) C/T
NM_024528.4(NKAP):c.1082G>A (p.Arg361Gln)
MISSENSE
rs1603379772 Pathogenic: Intellectual developmental disorder, x-linked, syndromic, Hackmann-Di Donato type 119,930,079(-) A/G
NM_024528.4(NKAP):c.1010T>C (p.Ile337Thr)
MISSENSE
rs1603379779 Pathogenic: Intellectual developmental disorder, x-linked, syndromic, Hackmann-Di Donato type 119,930,091(-) C/T
NM_024528.4(NKAP):c.998G>A (p.Arg333Gln)
MISSENSE
rs1603379780 Pathogenic: Intellectual developmental disorder, x-linked, syndromic, Hackmann-Di Donato type 119,930,100(-) C/T
NM_024528.4(NKAP):c.989G>A (p.Arg330His)
MISSENSE
rs1603379781 Uncertain Significance: Intellectual developmental disorder, x-linked, syndromic, Hackmann-Di Donato type; Inborn genetic diseases 119,930,101(-) G/A
NM_024528.4(NKAP):c.988C>T (p.Arg330Cys)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for NKAP Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for NKAP Gene

Variant ID Type Subtype PubMed ID
esv26416 CNV gain 19812545
esv2758888 CNV gain 17122850
esv3574425 CNV loss 25503493
nsv425243 CNV deletion 16902084
nsv7059 CNV insertion 18451855
nsv9969 CNV gain 18304495

Variation tolerance for NKAP Gene

Residual Variation Intolerance Score: 30.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.04; 68.69% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NKAP Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NKAP
Leiden Open Variation Database (LOVD)
NKAP

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NKAP Gene

Disorders for NKAP Gene

MalaCards: The human disease database

(2) MalaCards diseases for NKAP Gene - From: OMI, CVR, GTR, SWI, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search NKAP in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

NKAP_HUMAN
  • Intellectual developmental disorder, X-linked, syndromic, Hackman-Di Donato type (MRXSHD) [MIM:301039]: An X-linked recessive disorder characterized by impaired intellectual development, global developmental delay, hypotonia, joint contractures, behavioral abnormalities, Marfanoid habitus, scoliosis, and mildly dysmorphic facies. {ECO:0000269 PubMed:26358559, ECO:0000269 PubMed:31587868}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for NKAP

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with NKAP: view

No data available for Genatlas for NKAP Gene

Publications for NKAP Gene

  1. Missense Mutations in NKAP Cause a Disorder of Transcriptional Regulation Characterized by Marfanoid Habitus and Cognitive Impairment. (PMID: 31587868) Fiordaliso SK … Izumi K (American journal of human genetics 2019) 3 4 72
  2. Identification of a nuclear protein that promotes NF-kappaB activation. (PMID: 14550261) Chen D … Shu HB (Biochemical and biophysical research communications 2003) 2 3 4
  3. Tentative clinical diagnosis of Lujan-Fryns syndrome--A conglomeration of different genetic entities? (PMID: 26358559) Hackmann K … Di Donato N (American journal of medical genetics. Part A 2016) 4 72
  4. Association of genetic profiles to Crohn's disease by linear combinations of single nucleotide polymorphisms. (PMID: 18804983) D'Addabbo A … Ancona N (Artificial intelligence in medicine 2009) 3 40
  5. NKAP is a transcriptional repressor of notch signaling and is required for T cell development. (PMID: 19409814) Pajerowski AG … Shapiro VS (Immunity 2009) 3 4

Products for NKAP Gene

Sources for NKAP Gene