NCK1

protein-coding

NCK adaptor protein 1, the group of SH2 domain containing

Gene summary

The protein encoded by this gene is one of the signaling and transforming proteins containing Src homology 2 and 3 (SH2 and SH3) domains. It is located in the cytoplasm and is an adaptor protein involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as RAS. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Jun 2010]

Previous symbols:

MANE transcript

NM_001291999.2

Inheritance

—

ClinVar variants

U:29B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr3:136,862,208-136,951,606

External References & Databases

Ensembl (ENSG00000158092)

Transcript & Mutation Effects

hg38 • Region Span ~89.4 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 NCK1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 28

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001291999.2. 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			28 clinvar		1 clinvar	29
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	29	1	1	31

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001291999.2	RefSeq	NP_001278928.1	3	MANE Select
ENST00000481752.6	Ensembl	ENSP00000417273.1	3	MANE Select
NM_001190796.3	RefSeq	NP_001177725.1	3	Standard
NM_006153.6	RefSeq	NP_006144.1	3	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)
Angiogenesis overview

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

Molecular Function

protein kinase inhibitor activity
SH3/SH2 adaptor activity
signaling receptor binding
protein binding
cytoskeletal adaptor activity

Cellular Component

protein phosphatase type 1 complex
nucleus
cytoplasm
endoplasmic reticulum
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000481752
Coding exons: 3
Length: 87616
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125745
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.27	150	201	0.748	0.0000101	2486
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000065	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0.00056	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

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}.;

Recessive Scores

pRec: 0.611

Intolerance Scores

LoFtool: 0.485
RVIS EVS: 0.13
RVIS percentile EVS: 63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.945

Gene Damage Prediction

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