MINK1

Chr 17

misshapen like kinase 1

Also known as: B55, MAP4K6, MEKKK 6, MINK, YSK2, ZC3

NCBI Gene: 50488ENSG00000141503UniProt: Q8N4C8

This gene encodes a serine/threonine kinase belonging to the germinal center kinase (GCK) family. The protein is structurally similar to the kinases that are related to NIK and may belong to a distinct subfamily of NIK-related kinases within the GCK family. Studies of the mouse homolog indicate an up-regulation of expression in the course of postnatal mouse cerebral development and activation of the cJun N-terminal kinase (JNK) and the p38 pathways. [provided by RefSeq, Mar 2016]

229
ClinVar variants
24
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MINK1
⚡
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.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 181 VUS of 229 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.13LOEUF
pLI 1.000
Z-score 7.76
OE 0.06 (0.03–0.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.08Z-score
OE missense 0.60 (0.55–0.64)
483 obs / 810.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.03–0.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.55–0.64)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 5 / 79.8Missense obs/exp: 483 / 810.0Syn Z: -1.25

ClinVar Variant Classifications

229 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic2
VUS181
Likely Benign15
Benign9
22
Pathogenic
2
Likely Pathogenic
181
VUS
15
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
21
0
22
Likely Pathogenic
0
0
2
0
2
VUS
0
160
21
0
181
Likely Benign
0
6
2
7
15
Benign
0
0
7
2
9
Total1166539229

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

View in ClinVar →

Protein Context — Lollipop Plot

MINK1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MINK1 deficiency stimulates nucleus pulposus cell pyroptosis and exacerbates intervertebral disc degeneration.
Zhan K et al.·Int Immunopharmacol
2024
STRIPAK complexes: structure, biological function, and involvement in human diseases.
Hwang J et al.·Int J Biochem Cell Biol
2014Review
CRISPR-based kinome-screening revealed MINK1 as a druggable player to rewire 5FU-resistance in OSCC through AKT/MDM2/p53 axis.
Mohanty S et al.·Oncogene
2022
Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer's disease.
Broce IJ et al.·Acta Neuropathol
2019
The ATM Kinase Inhibitor AZD0156 Is a Potent Inhibitor of Plasmodium Phosphatidylinositol 4-Kinase (PI4Kβ) and Is an Attractive Candidate for Medicinal Chemistry Optimization Against Malaria.
Woodland JG et al.·Angew Chem Int Ed Engl
2025
Mapping effector genes at lupus GWAS loci using promoter Capture-C in follicular helper T cells.
Su C et al.·Nat Commun
2020
2,8-Disubstituted-1,5-naphthyridines as Dual Inhibitors of Plasmodium falciparum Phosphatidylinositol-4-kinase and Hemozoin Formation with In Vivo Efficacy.
Dziwornu GA et al.·J Med Chem
2024
Comprehensive Evaluation of the Genetic Basis of Keratoconus: New Perspectives for Clinical Translation.
Cerván-Martín M et al.·Invest Ophthalmol Vis Sci
2024
Normal tissue adjacent to tumor expression profile analysis developed and validated a prognostic model based on Hippo-related genes in hepatocellular carcinoma.
Pan Q et al.·Cancer Med
2021Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools