This gene encodes a member of the HEM family of tissue-specific transmembrane proteins which are highly conserved from invertebrates through mammals. This gene is only expressed in hematopoietic cells. The encoded protein is a part of the Scar/WAVE complex which plays an important role in regulating cell shape in both metazoans and plants. Alternatively spliced transcript varia... See more...

Aliases for NCKAP1L Gene

Aliases for NCKAP1L Gene

  • NCK Associated Protein 1 Like 2 3 5
  • Hematopoietic Protein 1 2 3 4
  • Nck-Associated Protein 1-Like 3 4
  • HEM1 3 4
  • Membrane-Associated Protein Hem-1 3
  • Membrane-Associated Protein HEM-1 4
  • NCKAP1L 5
  • IMD72 3

External Ids for NCKAP1L Gene

Previous HGNC Symbols for NCKAP1L Gene

  • HEM1

Previous GeneCards Identifiers for NCKAP1L Gene

  • GC12P053178
  • GC12P054891
  • GC12P051930

Summaries for NCKAP1L Gene

Entrez Gene Summary for NCKAP1L Gene

  • This gene encodes a member of the HEM family of tissue-specific transmembrane proteins which are highly conserved from invertebrates through mammals. This gene is only expressed in hematopoietic cells. The encoded protein is a part of the Scar/WAVE complex which plays an important role in regulating cell shape in both metazoans and plants. Alternatively spliced transcript variants encoding different isoforms have been found.[provided by RefSeq, May 2010]

GeneCards Summary for NCKAP1L Gene

NCKAP1L (NCK Associated Protein 1 Like) is a Protein Coding gene. Diseases associated with NCKAP1L include Immunodeficiency 72 With Autoinflammation and Bronchus Cancer. Among its related pathways are RET signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity. An important paralog of this gene is NCKAP1.

UniProtKB/Swiss-Prot Summary for NCKAP1L Gene

  • Essential hematopoietic-specific regulator of the actin cytoskeleton (Probable). Controls lymphocyte development, activation, proliferation and homeostasis, erythrocyte membrane stability, as well as phagocytosis and migration by neutrophils and macrophages (PubMed:16417406, PubMed:17696648). Component of the WAVE2 complex which signals downstream of RAC to stimulate F-actin polymerization. Required for stabilization and/or translation of the WAVE2 complex proteins in hematopoietic cells (By similarity). Exhibits complex cycles of activation and inhibition to generate waves of propagating the assembly with actin (PubMed:16417406). Also involved in mechanisms WAVE-independent to regulate myosin and actin polymerization during neutrophil chemotaxis (PubMed:17696648).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NCKAP1L Gene

Genomics for NCKAP1L Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NCKAP1L 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 NCKAP1L on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NCKAP1L

Top Transcription factor binding sites by QIAGEN in the NCKAP1L gene promoter:
  • AREB6
  • FOXJ2
  • FOXJ2 (long isoform)
  • Pax-6
  • POU2F1
  • POU2F1a
  • TBP
  • TFIID

Genomic Locations for NCKAP1L Gene

Latest Assembly
chr12:54,497,752-54,548,243
(GRCh38/hg38)
Size:
50,492 bases
Orientation:
Plus strand

Previous Assembly
chr12:54,891,536-54,942,027
(GRCh37/hg19 by Entrez Gene)
Size:
50,492 bases
Orientation:
Plus strand

chr12:54,891,495-54,937,726
(GRCh37/hg19 by Ensembl)
Size:
46,232 bases
Orientation:
Plus strand

Genomic View for NCKAP1L Gene

Genes around NCKAP1L on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NCKAP1L Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NCKAP1L Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NCKAP1L Gene

Proteins for NCKAP1L Gene

  • Protein details for NCKAP1L Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P55160-NCKPL_HUMAN
    Recommended name:
    Nck-associated protein 1-like
    Protein Accession:
    P55160
    Secondary Accessions:
    • B4DUT5
    • Q52LW0

    Protein attributes for NCKAP1L Gene

    Size:
    1127 amino acids
    Molecular mass:
    128153 Da
    Quaternary structure:
    • In hematopoietic cells, component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1L/HEM1 and WASF2/WAVE2 (PubMed:16417406). Interacts with ARHGAP4, PIK3C3/VPS34 and PPP1R12A/MYPT1 (PubMed:16417406).
    SequenceCaution:
    • Sequence=AAA35964.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for NCKAP1L Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NCKAP1L Gene

Post-translational modifications for NCKAP1L Gene

  • Ubiquitination at Lys10, Lys60, Lys61, Lys40, Lys42, Lys49, Lys326, and Lys349
  • Modification sites at PhosphoSitePlus

Other Protein References for NCKAP1L Gene

No data available for DME Specific Peptides for NCKAP1L Gene

Domains & Families for NCKAP1L Gene

Gene Families for NCKAP1L Gene

Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted membrane proteins

Protein Domains for NCKAP1L Gene

Suggested Antigen Peptide Sequences for NCKAP1L Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ58731, highly similar to Nck-associated protein 1-like (B4DUT5_HUMAN)
  • Membrane-associated protein HEM-1 (NCKPL_HUMAN)
  • NCKAP1L protein (Q5XG97_HUMAN)
  • NCKAP1L protein (Q6P1M2_HUMAN)
  • NCKAP1L protein (Q9BV52_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P55160

UniProtKB/Swiss-Prot:

NCKPL_HUMAN :
  • Belongs to the HEM-1/HEM-2 family.
Family:
  • Belongs to the HEM-1/HEM-2 family.
genes like me logo Genes that share domains with NCKAP1L: view

Function for NCKAP1L Gene

Molecular function for NCKAP1L Gene

UniProtKB/Swiss-Prot Function:
Essential hematopoietic-specific regulator of the actin cytoskeleton (Probable). Controls lymphocyte development, activation, proliferation and homeostasis, erythrocyte membrane stability, as well as phagocytosis and migration by neutrophils and macrophages (PubMed:16417406, PubMed:17696648). Component of the WAVE2 complex which signals downstream of RAC to stimulate F-actin polymerization. Required for stabilization and/or translation of the WAVE2 complex proteins in hematopoietic cells (By similarity). Exhibits complex cycles of activation and inhibition to generate waves of propagating the assembly with actin (PubMed:16417406). Also involved in mechanisms WAVE-independent to regulate myosin and actin polymerization during neutrophil chemotaxis (PubMed:17696648).

Phenotypes From GWAS Catalog for NCKAP1L Gene

Gene Ontology (GO) - Molecular Function for NCKAP1L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005096 GTPase activator activity IMP 16417406
GO:0005515 protein binding IPI 16417406
GO:0030295 protein kinase activator activity IMP 16417406
GO:0031267 small GTPase binding IBA --
GO:0044877 protein-containing complex binding IDA 16417406
genes like me logo Genes that share ontologies with NCKAP1L: view
genes like me logo Genes that share phenotypes with NCKAP1L: view

Human Phenotype Ontology for NCKAP1L Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NCKAP1L

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for NCKAP1L Gene

Localization for NCKAP1L Gene

Subcellular locations from UniProtKB/Swiss-Prot for NCKAP1L Gene

Cell membrane. Single-pass membrane protein. Cytoplasmic side. Cytoplasm. Note=Localizes to the leading edge of polarized neutrophils. {ECO:0000269 PubMed:16417406, ECO:0000269 PubMed:17696648}.

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 NCKAP1L gene
Compartment Confidence
plasma membrane 5
cytosol 5
extracellular 4
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 1
endosome 1
lysosome 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (1)
  • Plasma membrane (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NCKAP1L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane NAS 1932118
GO:0016020 membrane TAS,HDA 19946888
genes like me logo Genes that share ontologies with NCKAP1L: view

Pathways & Interactions for NCKAP1L Gene

genes like me logo Genes that share pathways with NCKAP1L: view

Gene Ontology (GO) - Biological Process for NCKAP1L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000902 cell morphogenesis IBA 21873635
GO:0001782 B cell homeostasis ISS --
GO:0002262 myeloid cell homeostasis ISS --
GO:0006935 chemotaxis IDA 16417406
GO:0016477 cell migration IBA 21873635
genes like me logo Genes that share ontologies with NCKAP1L: view

No data available for SIGNOR curated interactions for NCKAP1L Gene

Drugs & Compounds for NCKAP1L Gene

No Compound Related Data Available

Transcripts for NCKAP1L Gene

mRNA/cDNA for NCKAP1L Gene

2 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
8 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 NCKAP1L

Alternative Splicing Database (ASD) splice patterns (SP) for NCKAP1L Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18a · 18b ^ 19 ^ 20 ^ 21a · 21b ^
SP1: - - -
SP2:
SP3:
SP4:
SP5:
SP6:

ExUns: 22a · 22b ^ 23 ^ 24 ^ 25 ^ 26 ^ 27a · 27b ^ 28 ^ 29a · 29b ^ 30 ^ 31 ^ 32
SP1: - -
SP2:
SP3:
SP4:
SP5:
SP6:

Relevant External Links for NCKAP1L Gene

GeneLoc Exon Structure for
NCKAP1L

Expression for NCKAP1L Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NCKAP1L Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NCKAP1L Gene

This gene is overexpressed in Whole Blood (x13.2) and Spleen (x4.3).

Protein differential expression in normal tissues from HIPED for NCKAP1L Gene

This gene is overexpressed in Lymph node (25.4) and Peripheral blood mononuclear cells (10.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NCKAP1L Gene



Protein tissue co-expression partners for NCKAP1L Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NCKAP1L

SOURCE GeneReport for Unigene cluster for NCKAP1L Gene:

Hs.182014

mRNA Expression by UniProt/SwissProt for NCKAP1L Gene:

P55160-NCKPL_HUMAN
Tissue specificity: Expressed only in cells of hematopoietic origin (PubMed:7643388, PubMed:1932118). Expressed in neutrophils (at protein level) (PubMed:16417406).

Evidence on tissue expression from TISSUES for NCKAP1L Gene

  • Blood(4.5)
  • Intestine(4.4)
  • Liver(4.3)
  • Nervous system(3.7)
  • Spleen(2.2)
  • Lymph node(2.2)
genes like me logo Genes that share expression patterns with NCKAP1L: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for NCKAP1L Gene

Orthologs for NCKAP1L Gene

This gene was present in the common ancestor of animals.

Orthologs for NCKAP1L Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NCKAP1L 29 30
  • 99.54 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NCKAP1L 29 30
  • 91.92 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NCKAP1L 29 30
  • 91.42 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Nckap1l 29 16 30
  • 89.68 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Nckap1l 29
  • 88.99 (n)
Oppossum
(Monodelphis domestica)
Mammalia NCKAP1L 30
  • 86 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 84 (a)
OneToMany
-- 30
  • 78 (a)
OneToMany
Chicken
(Gallus gallus)
Aves NCKAP1L 29 30
  • 71.13 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 71 (a)
OneToMany
-- 30
  • 68 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia nckap1l 29
  • 68.63 (n)
Zebrafish
(Danio rerio)
Actinopterygii zgc:172352 29
  • 64.13 (n)
NCKAP1L 30
  • 60 (a)
OneToOne
Dr.26103 29
Fruit Fly
(Drosophila melanogaster)
Insecta Hem 30
  • 47 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea gex-3 30
  • 36 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.9782 30
  • 47 (a)
OneToMany
Species where no ortholog for NCKAP1L was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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 NCKAP1L Gene

ENSEMBL:
Gene Tree for NCKAP1L (if available)
TreeFam:
Gene Tree for NCKAP1L (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NCKAP1L: view image
Alliance of Genome Resources:
Additional Orthologs for NCKAP1L

Paralogs for NCKAP1L Gene

Paralogs for NCKAP1L Gene

(1) SIMAP similar genes for NCKAP1L Gene using alignment to 5 proteins:

  • NCKPL_HUMAN
  • F8W050_HUMAN
  • Q5XG97_HUMAN
  • Q6P1M2_HUMAN
  • Q9BV52_HUMAN
genes like me logo Genes that share paralogs with NCKAP1L: view

Variants for NCKAP1L Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NCKAP1L Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
976846 Pathogenic: Immunodeficiency 72 with autoinflammation 54,516,973(+) C/T
NM_005337.5(NCKAP1L):c.1076C>T (p.Pro359Leu)
MISSENSE
976847 Pathogenic: Immunodeficiency 72 with autoinflammation 54,519,262(+) G/C
NM_005337.5(NCKAP1L):c.1555G>C (p.Val519Leu)
MISSENSE
976848 Pathogenic: Immunodeficiency 72 with autoinflammation 54,517,548(+) A/G
NM_005337.5(NCKAP1L):c.1111A>G (p.Met371Val)
MISSENSE
976849 Pathogenic: Immunodeficiency 72 with autoinflammation 54,511,840(+) G/T
NM_005337.5(NCKAP1L):c.773G>T (p.Arg258Leu)
MISSENSE
rs2270581 -- p.Ser402Leu

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for NCKAP1L 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 NCKAP1L Gene

Variant ID Type Subtype PubMed ID
esv3391984 CNV insertion 20981092
nsv508674 CNV deletion 20534489
nsv525674 CNV loss 19592680
nsv832421 CNV gain 17160897

Variation tolerance for NCKAP1L Gene

Residual Variation Intolerance Score: 5.97% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.31; 70.55% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NCKAP1L Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NCKAP1L
Leiden Open Variation Database (LOVD)
NCKAP1L

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NCKAP1L Gene

Disorders for NCKAP1L Gene

MalaCards: The human disease database

(4) MalaCards diseases for NCKAP1L Gene - From: OMI, CVR, COP, and GCD

Disorder Aliases PubMed IDs
immunodeficiency 72 with autoinflammation
  • imd72
bronchus cancer
  • malignant neoplasm of bronchus and lung
bronchus adenoma
  • adenoma of the bronchus
progesterone-receptor positive breast cancer
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for NCKAP1L

genes like me logo Genes that share disorders with NCKAP1L: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NCKAP1L Gene

Publications for NCKAP1L Gene

  1. Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis. (PMID: 16417406) Weiner OD … Kirschner MW (PLoS biology 2006) 3 4 22
  2. Hem-1, a potential membrane protein, with expression restricted to blood cells. (PMID: 1932118) Hromas R … Kaushansky K (Biochimica et biophysica acta 1991) 2 3 4
  3. HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease. (PMID: 32647003) Cook SA … Lenardo MJ (Science (New York, N.Y.) 2020) 3 72
  4. An actin-based wave generator organizes cell motility. (PMID: 17696648) Weiner OD … Kirschner MW (PLoS biology 2007) 3 4
  5. The HEM proteins: a novel family of tissue-specific transmembrane proteins expressed from invertebrates through mammals with an essential function in oogenesis. (PMID: 7643388) Baumgartner S … Hromas R (Journal of molecular biology 1995) 3 4

Products for NCKAP1L Gene

Sources for NCKAP1L Gene