NCK1
NCK adaptor protein 1, the group of SH2 domain containing
Basic information
Region (hg38): 3:136862208-136951606
Previous symbols: [ "NCK" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCK1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 13 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 13 | 0 | 1 |
Variants in NCK1
This is a list of pathogenic ClinVar variants found in the NCK1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-136928099-A-G | not specified | Uncertain significance (Apr 26, 2024) | ||
| 3-136928180-A-G | not specified | Uncertain significance (Jan 17, 2024) | ||
| 3-136928189-G-A | not specified | Uncertain significance (Nov 21, 2022) | ||
| 3-136945747-A-G | not specified | Uncertain significance (Jan 11, 2023) | ||
| 3-136945789-C-T | not specified | Uncertain significance (Aug 12, 2021) | ||
| 3-136945802-A-G | not specified | Uncertain significance (Nov 21, 2024) | ||
| 3-136945852-A-G | not specified | Uncertain significance (Mar 29, 2022) | ||
| 3-136945868-A-G | not specified | Uncertain significance (Jan 23, 2023) | ||
| 3-136945910-A-C | not specified | Uncertain significance (Feb 12, 2024) | ||
| 3-136945965-A-T | Likely benign (Aug 01, 2024) | |||
| 3-136945976-A-C | not specified | Uncertain significance (Mar 30, 2024) | ||
| 3-136946128-G-C | Benign (Apr 04, 2018) | |||
| 3-136946173-C-T | not specified | Uncertain significance (Nov 17, 2022) | ||
| 3-136948274-G-A | not specified | Uncertain significance (Jul 15, 2021) | ||
| 3-136948292-G-A | not specified | Uncertain significance (Jan 03, 2024) | ||
| 3-136948318-A-C | not specified | Uncertain significance (Nov 24, 2024) | ||
| 3-136948318-A-T | not specified | Uncertain significance (Jan 02, 2024) | ||
| 3-136948364-A-T | not specified | Uncertain significance (Dec 28, 2022) | ||
| 3-136948380-A-G | not specified | Uncertain significance (May 17, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NCK1 | protein_coding | protein_coding | ENST00000481752 | 3 | 87616 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00207 | 0.980 | 125728 | 0 | 17 | 125745 | 0.0000676 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.27 | 150 | 201 | 0.748 | 0.0000101 | 2486 |
| Missense in Polyphen | 42 | 85.464 | 0.49144 | 1138 | ||
| Synonymous | -0.245 | 74 | 71.4 | 1.04 | 0.00000346 | 690 |
| Loss of Function | 2.08 | 7 | 15.9 | 0.439 | 8.25e-7 | 195 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000647 | 0.0000647 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000114 | 0.000109 |
| Finnish | 0.000324 | 0.000323 |
| European (Non-Finnish) | 0.0000267 | 0.0000264 |
| Middle Eastern | 0.000114 | 0.000109 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000562 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: Adapter protein which associates with tyrosine- phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. Modulates the activation of EIF2AK2/PKR by dsRNA. May play a role in cell adhesion and migration through interaction with ephrin receptors. {ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:16835242, ECO:0000269|PubMed:17803907, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:9430661}.;
- Pathway
- T cell receptor signaling pathway - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Axon guidance - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Angiogenesis overview;Pathogenic Escherichia coli infection;B Cell Receptor Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Primary Focal Segmental Glomerulosclerosis FSGS;Rac1-Pak1-p38-MMP-2 pathway;Association Between Physico-Chemical Features and Toxicity Associated Pathways;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;VEGFA-VEGFR2 Signaling Pathway;EGF-EGFR Signaling Pathway;ErbB Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;Developmental Biology;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Signal Transduction;VEGFA-VEGFR2 Pathway;y branching of actin filaments;Prolactin;Generation of second messenger molecules;TCR signaling;Signaling by the B Cell Receptor (BCR);Signaling by PDGF;Fcgamma receptor (FCGR) dependent phagocytosis;TCR;Innate Immune System;Immune System;RHO GTPases Activate WASPs and WAVEs;Adaptive Immune System;Activation of RAC1;BCR;RHO GTPase Effectors;Signaling by Rho GTPases;DCC mediated attractive signaling;BDNF;EGFR1;PDGF;Regulation of actin dynamics for phagocytic cup formation;Netrin-1 signaling;Signaling events regulated by Ret tyrosine kinase;Downstream signal transduction;Signaling by ROBO receptors;Signaling by VEGF;Angiopoietin receptor Tie2-mediated signaling;Axon guidance;Signaling by Receptor Tyrosine Kinases;Nephrin family interactions;Cell-Cell communication;Stabilization and expansion of the E-cadherin adherens junction;Insulin Pathway;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Netrin-mediated signaling events;Signaling events mediated by focal adhesion kinase;EPHB forward signaling;Arf6 signaling events;PDGFR-beta signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2;TCR signaling in naïve CD4+ T cells;Nephrin/Neph1 signaling in the kidney podocyte;VEGFR1 specific signals
(Consensus)
Recessive Scores
- pRec
- 0.611
Intolerance Scores
- loftool
- 0.485
- rvis_EVS
- 0.13
- rvis_percentile_EVS
- 63
Haploinsufficiency Scores
- pHI
- 0.853
- hipred
- Y
- hipred_score
- 0.738
- ghis
- 0.579
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.945
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nck1
- Phenotype
- normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype;
Gene ontology
- Biological process
- negative regulation of protein kinase activity;substrate-dependent cell migration, cell extension;actin filament organization;signal complex assembly;positive regulation of neuron projection development;lamellipodium assembly;regulation of cell migration;positive regulation of actin filament polymerization;negative regulation of peptidyl-serine phosphorylation;positive regulation of translation in response to endoplasmic reticulum stress;Fc-gamma receptor signaling pathway involved in phagocytosis;positive regulation of T cell proliferation;T cell activation;positive regulation of transcription by RNA polymerase II;negative regulation of insulin receptor signaling pathway;vascular endothelial growth factor receptor signaling pathway;ephrin receptor signaling pathway;T cell receptor signaling pathway;response to other organism;negative regulation of cell death;peptidyl-serine dephosphorylation;positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway;positive regulation of cap-dependent translational initiation;positive regulation of cap-independent translational initiation;negative regulation of PERK-mediated unfolded protein response;negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation;negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
- Cellular component
- protein phosphatase type 1 complex;nucleus;cytoplasm;endoplasmic reticulum;cytosol;ribosome;plasma membrane;cell-cell junction;vesicle membrane
- Molecular function
- protein kinase inhibitor activity;SH3/SH2 adaptor activity;signaling receptor binding;protein binding;cytoskeletal adaptor activity;protein domain specific binding;receptor signaling complex scaffold activity;protein binding, bridging;receptor tyrosine kinase binding;cadherin binding;ephrin receptor binding;molecular adaptor activity;eukaryotic initiation factor eIF2 binding