NCK2

protein-coding

NCK adaptor protein 2, the group of SH2 domain containing

Gene summary

This gene encodes a member of the NCK family of adaptor proteins. The protein contains three SH3 domains and one SH2 domain. The protein has no known catalytic function but has been shown to bind and recruit various proteins involved in the regulation of receptor protein tyrosine kinases. It is through these regulatory activities that this protein is believed to be involved in cytoskeletal reorganization. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003581.5

Inheritance

—

ClinVar variants

U:36B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr2:105,744,912-105,894,274

External References & Databases

Ensembl (ENSG00000071051)

Transcript & Mutation Effects

hg38 • Region Span ~149.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NCK2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 34

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003581.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense			33 clinvar			33
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	36	1	0	37

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 90 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003581.5	RefSeq	NP_003572.2	3	MANE Select
ENST00000233154.9	Ensembl	ENSP00000233154.4	3	MANE Select
NM_001004720.3	RefSeq	NP_001004720.1	3	Standard
NM_001004722.4	RefSeq	NP_001004722.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

immunological synapse formation
actin filament organization
signal transduction
signal complex assembly
epidermal growth factor receptor signaling pathway

Molecular Function

phosphotyrosine residue binding
SH3/SH2 adaptor activity
protein binding
cytoskeletal adaptor activity
receptor signaling complex scaffold activity

Cellular Component

cytoplasm
endoplasmic reticulum
cytosol
vesicle membrane
postsynaptic density

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000233154
Coding exons: 3
Length: 149377
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125725
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.45	161	275	0.584	0.0000202	2481
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.259

Intolerance Scores

LoFtool: 0.223
RVIS EVS: -0.71
RVIS percentile EVS: 14.4

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.881

Gene Damage Prediction

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