NCK1

Chr 3

NCK adaptor protein 1

Also known as: NCK, NCKalpha, nck-1

NCBI Gene: 4690 ENSG00000158092 UniProt: P16333 OMIM: 600508

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.82

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.002

Z-score 2.08

OE 0.44 (0.25–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.27Z-score

OE missense 0.75 (0.65–0.86)

150 obs / 200.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.25–0.82)

0≤0.351.4

Missense OE?0.75 (0.65–0.86)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 7 / 15.9Missense obs/exp: 150 / 200.5Syn Z: -0.25

Background carrier burden — how many people carry a rare variant somewhere in NCK1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

401 rare PASS variants

Rare truncating (LoF)

1 in 4,300

49 rare PASS variants

Rare synonymous (reference)

1 in 440

162 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NCK1. 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 180	1 in 3,500
South Asian	~43k	1 in 190	1 in 1,200
Remaining (unassigned)	~30k	1 in 150	≈ 1 in 9,700
European (Finnish)	~27k	1 in 2,100	1 in 3,000
Admixed American	~22k	1 in 320	1 in 2,100
African / African American	~21k	1 in 170	1 in 3,100
East Asian	~20k	1 in 150	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 2,200	1 in 1,400
Middle Eastern	~2,884	1 in 260	≈ 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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓