PEAK1

Chr 15

pseudopodium enriched atypical kinase 1

Also known as: SGK269

NCBI Gene: 79834 ENSG00000173517 UniProt: Q9H792

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]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.44

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.001

Z-score 4.96

OE 0.29 (0.20–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.18Z-score

OE missense 1.02 (0.96–1.07)

940 obs / 924.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.29 (0.20–0.44)

0≤0.351.4

Missense OE?1.02 (0.96–1.07)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 17 / 57.7Missense obs/exp: 940 / 924.8Syn Z: 1.18

Background carrier burden — how many people carry a rare variant somewhere in PEAK1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 28

2,182 rare PASS variants

Rare truncating (LoF)

1 in 2,000

162 rare PASS variants

Rare synonymous (reference)

1 in 68

777 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PEAK1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 41	1 in 2,000
South Asian	~43k	1 in 32	1 in 1,600
Remaining (unassigned)	~30k	1 in 25	1 in 3,000
European (Finnish)	~27k	1 in 130	1 in 2,700
Admixed American	~22k	1 in 27	1 in 1,400
African / African American	~21k	1 in 30	1 in 2,200
East Asian	~20k	1 in 31	1 in 4,000
Ashkenazi Jewish	~13k	1 in 98	1 in 710
Middle Eastern	~2,884	1 in 31	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓