PEAK1

protein-coding

pseudopodium enriched atypical kinase 1

Gene summary

This gene encodes a non-receptor tyrosine kinase that is a member of the new kinase family three (NFK3) family. In migrating cells, the encoded protein is associated with the actin cytoskeleton and focal adhesions and promotes developing focal adhesion elongation. This protein may play a role in the regulation of cell migration, proliferation and cancer metastasis. [provided by RefSeq, Mar 2014]

MANE transcript

NM_001385026.1

Inheritance

—

ClinVar variants

U:267B:35

Top phenotype

PEAK1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr15:77,100,656-77,420,144

External References & Databases

Ensembl (ENSG00000173517)

Transcript & Mutation Effects

hg38 • Region Span ~319.5 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 PEAK1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 261

PEAK1-related disorderTotal: 28

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001385026.1. 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			2 clinvar	17 clinvar	1 clinvar	20
missense			260 clinvar	13 clinvar	4 clinvar	277
nonsense			4 clinvar			4
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	267	30	5	302

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001385026.1	RefSeq	NP_001371955.1	4	MANE Select
ENST00000682557.1	Ensembl	ENSP00000507603.1	4	MANE Select
NM_001385027.1	RefSeq	NP_001371956.1	2	Standard
NM_001387085.1	RefSeq	NP_001374014.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein phosphorylation
cell migration
peptidyl-tyrosine phosphorylation
substrate adhesion-dependent cell spreading
protein autophosphorylation

Molecular Function

protein kinase activity
non-membrane spanning protein tyrosine kinase activity
protein binding
ATP binding
identical protein binding

Cellular Component

cytoplasm
focal adhesion
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000560626
Coding exons: 4
Length: 312016
Individuals with no LoFs: 124766
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 124811
p: 0.000180

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.177	940	925	1.02	0.0000498	11517
Missense (PolyPhen)		358	367.33	0.97461		4534
Synonymous	1.18	309	336	0.918	0.0000171	3471
Loss of Function	4.96	17	57.7	0.295	0.00000396	682

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.00045	0.00045	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable catalytically inactive kinase. Scaffolding protein that regulates the cytoskeleton to control cell spreading and migration by modulating focal adhesion dynamics (PubMed:23105102, PubMed:20534451). Acts as a scaffold for mediating EGFR signaling (PubMed:23846654). {ECO:0000269|PubMed:20534451, ECO:0000269|PubMed:23105102, ECO:0000269|PubMed:23846654}.;

Intolerance Scores

RVIS EVS: -1.29
RVIS percentile EVS: 5

Essentials

Essential (CRISPR): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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