PRAG1

Chr 8

PEAK1 related, kinase-activating pseudokinase 1

Also known as: NACK, PEAK2, PRAGMIN, SGK223

NCBI Gene: 157285 ENSG00000275342 UniProt: Q86YV5

This gene encodes a catalytically inactive protein kinase that functions as a scaffold protein, regulating neurite outgrowth through RND2-RhoA signaling, promoting Src family kinase signaling by controlling CSK localization, and serving as a coactivator of Notch signaling. Pathogenic variants cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. The phenotype primarily affects the nervous system with early childhood onset.

ResearchSummary from RefSeq, UniProt

This gene encodes an enzyme that belongs to the tyrosine protein kinase family. A similar protein in rat binds to Rho family GTPase 2 (Rnd2) and regulates neurite outgrowth via activation of Ras homolog gene family, member A (RhoA). [provided by RefSeq, Mar 2014]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (2)

gnomad: Error: Gene not found

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in PRAG1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 20

2,715 rare PASS variants

Rare truncating (LoF)

1 in 470

271 rare PASS variants

Rare synonymous (reference)

1 in 33

1,122 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRAG1. 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 31	1 in 480
South Asian	~43k	1 in 19	1 in 920
Remaining (unassigned)	~30k	1 in 19	1 in 460
European (Finnish)	~27k	1 in 78	1 in 1,100
Admixed American	~22k	1 in 19	1 in 680
African / African American	~21k	1 in 22	1 in 460
East Asian	~20k	1 in 21	1 in 510
Ashkenazi Jewish	~13k	1 in 52	≈ 1 in 11,000
Middle Eastern	~2,884	1 in 19	≈ 1 in 710

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓