TNIK

Chr 3

TRAF2 and NCK interacting kinase

Also known as: MAP4K7, MRT54

NCBI Gene: 23043 ENSG00000154310 UniProt: Q9UKE5

This serine/threonine kinase functions as an essential activator of the Wnt signaling pathway and plays roles in neuronal dendrite development and the Hippo signaling pathway. Mutations cause autosomal recessive intellectual developmental disorder. The gene is highly constrained against loss-of-function variants (pLI ~1.0), indicating intolerance to haploinsufficiency in the general population.

ResearchSummary from RefSeq, OMIM, UniProt

Wnt signaling plays important roles in carcinogenesis and embryonic development. The protein encoded by this gene is a serine/threonine kinase that functions as an activator of the Wnt signaling pathway. Mutations in this gene are associated with an autosomal recessive form of cognitive disability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal recessive 54

Clinical highlights

Gene–disease validity (ClinGen)

Limited · non-syndromic intellectual disability · AR · ClinGen 2025

not for standalone diagnostic reporting

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

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 TNIK?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 73

1,253 rare PASS variants

Rare truncating (LoF)

1 in 2,800

99 rare PASS variants

Rare synonymous (reference)

1 in 68

637 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TNIK. 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 86	1 in 2,600
South Asian	~43k	1 in 82	1 in 3,600
Remaining (unassigned)	~30k	1 in 52	1 in 4,800
European (Finnish)	~27k	1 in 290	1 in 2,400
Admixed American	~22k	1 in 51	1 in 1,100
African / African American	~21k	1 in 69	1 in 900
East Asian	~20k	1 in 53	1 in 1,900
Ashkenazi Jewish	~13k	1 in 210	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 94	≈ 1 in 960

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.