STYK1

Chr 12

STY kinase 1

Also known as: NOK, SuRTK106

NCBI Gene: 55359 ENSG00000060140 UniProt: Q6J9G0 OMIM: 611433

STYK1 encodes a receptor protein tyrosine kinase that regulates cell proliferation, differentiation, and survival through MAP kinase and PI3K signaling pathways. Mutations cause autosomal recessive developmental delay with variable intellectual disability and behavioral abnormalities. The gene shows very low constraint against loss-of-function variants, consistent with a recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Receptor protein tyrosine kinases, like STYK1, play important roles in diverse cellular and developmental processes, such as cell proliferation, differentiation, and survival (Liu et al., 2004 [PubMed 15150103]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.19

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.19LOEUF

pLI 0.000

Z-score 0.88

OE 0.80 (0.55–1.19)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.03Z-score

OE missense 0.99 (0.89–1.11)

236 obs / 237.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.80 (0.55–1.19)

0≤0.351.4

Missense OE?0.99 (0.89–1.11)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 18 / 22.5Missense obs/exp: 236 / 237.3Syn Z: 0.74

Background carrier burden — how many people carry a rare variant somewhere in STYK1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

562 rare PASS variants

Rare truncating (LoF)

1 in 790

90 rare PASS variants

Rare synonymous (reference)

1 in 310

199 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for STYK1. 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 150	1 in 870
South Asian	~43k	1 in 110	1 in 2,100
Remaining (unassigned)	~30k	1 in 100	1 in 790
European (Finnish)	~27k	1 in 200	1 in 790
Admixed American	~22k	1 in 87	1 in 1,000
African / African American	~21k	1 in 92	1 in 560
East Asian	~20k	1 in 85	1 in 1,600
Ashkenazi Jewish	~13k	1 in 400	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 78	≈ 1 in 1,400

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