NCK2

NCK adaptor protein 2, the group of SH2 domain containing

Basic information

Region (hg38): 2:105744911-105894274

Links

ENSG00000071051 ∙ NCBI:8440 ∙ OMIM:604930 ∙ HGNC:7665 ∙ Uniprot:O43639 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NCK2 gene.

• Inborn genetic diseases (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCK2 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			6			6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	0	0

Variants in NCK2

This is a list of pathogenic ClinVar variants found in the NCK2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-105855127-G-A		not specified	Uncertain significance (Jan 30, 2024)
2-105881385-C-T		not specified	Uncertain significance (Oct 06, 2022)
2-105881390-G-A		not specified	Uncertain significance (Sep 30, 2021)
2-105881413-C-A		not specified	Uncertain significance (Jan 22, 2024)
2-105881433-A-T		not specified	Uncertain significance (Oct 13, 2023)
2-105881561-A-T		not specified	Uncertain significance (Sep 26, 2023)
2-105881657-G-T		not specified	Uncertain significance (Oct 03, 2022)
2-105881787-A-C		not specified	Uncertain significance (Nov 17, 2023)
2-105881847-A-G		not specified	Uncertain significance (Aug 28, 2023)
2-105881868-G-A		not specified	Uncertain significance (Sep 27, 2021)
2-105881933-G-A		not specified	Uncertain significance (Feb 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NCK2	protein_coding	protein_coding	ENST00000233154	3	149377

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.458	0.541	125720	0	5	125725	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.45	161	275	0.584	0.0000202	2481
Missense in Polyphen		72	145.41	0.49515		1353
Synonymous	0.471	131	138	0.949	0.0000121	745
Loss of Function	2.77	3	14.3	0.209	6.14e-7	157

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000267	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adapter protein which associates with tyrosine- phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1- dependent transcriptional activation in response to activated Ras signaling. {ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:16835242}.
• 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);Pathogenic Escherichia coli infection;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;EGF-EGFR Signaling Pathway;Developmental Biology;Signal Transduction;VEGFA-VEGFR2 Pathway;Signaling by PDGF;EPH-Ephrin signaling;Ephrin signaling;Activation of RAC1;BDNF;EGFR1;Downstream signal transduction;Ephrin B reverse signaling;Signaling by ROBO receptors;Signaling by VEGF;Axon guidance;Regulation of cortical dendrite branching;Integrin-linked kinase signaling;Signaling by Receptor Tyrosine Kinases;Nephrin family interactions;Cell-Cell communication;Insulin Pathway;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Signaling events mediated by focal adhesion kinase;Reelin signaling pathway;IGF1 pathway;PDGFR-beta signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2;Nephrin/Neph1 signaling in the kidney podocyte (Consensus)

Recessive Scores

• pRec: 0.259

Intolerance Scores

• loftool: 0.223
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.4

Haploinsufficiency Scores

• pHI: 0.248
• hipred: Y
• hipred_score: 0.825
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.881

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nck2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; embryo phenotype; 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); 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); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: immunological synapse formation;actin filament organization;signal transduction;signal complex assembly;epidermal growth factor receptor signaling pathway;regulation of epidermal growth factor-activated receptor activity;negative regulation of cell population proliferation;cell migration;lamellipodium assembly;positive regulation of actin filament polymerization;negative regulation of peptidyl-serine phosphorylation;positive regulation of translation in response to endoplasmic reticulum stress;positive regulation of T cell proliferation;T cell activation;positive regulation of transcription by RNA polymerase II;vascular endothelial growth factor receptor signaling pathway;ephrin receptor signaling pathway;dendritic spine development;positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway;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: cytoplasm;endoplasmic reticulum;cytosol;vesicle membrane;postsynaptic density
• Molecular function: phosphotyrosine residue binding;SH3/SH2 adaptor activity;protein binding;cytoskeletal adaptor activity;receptor signaling complex scaffold activity;protein-containing complex binding;scaffold protein binding