TNIK

Chr 3

TRAF2 and NCK interacting kinase

Also known as: MAP4K7, MRT54

NCBI Gene: 23043ENSG00000154310UniProt: 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
LOFmechanismLOEUF 0.18
Clinical Summary— TNIK
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Gene-Disease Validity (ClinGen)
non-syndromic intellectual disability · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 127 VUS of 252 total submissions
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 7.75
OE 0.10 (0.06–0.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
4.10Z-score
OE missense 0.58 (0.53–0.63)
436 obs / 753.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.10 (0.06–0.18)
0≤0.351.4
Missense OE0.58 (0.53–0.63)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 9 / 87.0Missense obs/exp: 436 / 753.0Syn Z: 0.42
DN
0.4982th %ile
GOF
0.6051th %ile
LOF
0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.18

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

252 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic2
VUS127
Likely Benign44
Benign14
21
Pathogenic
2
Likely Pathogenic
127
VUS
44
Likely Benign
14
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
20
0
21
Likely Pathogenic
0
0
2
0
2
VUS
1
122
3
1
127
Likely Benign
0
2
10
32
44
Benign
0
1
6
7
14
Total21254140208

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TNIK · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients