MINK1

Chr 17

misshapen like kinase 1

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

NCBI Gene: 50488 ENSG00000141503 UniProt: Q8N4C8

The protein is a serine/threonine kinase that regulates neuronal structure, synaptic density, dendrite complexity, and AMPA receptor trafficking, while also activating JNK and p38 MAPK pathways. Pathogenic variants cause autosomal dominant neurodevelopmental disorder with developmental delay, intellectual disability, and behavioral abnormalities. This gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.132), indicating that such variants are likely to be pathogenic.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.13

Clinical Summary— MINK1

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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

2 unique Pathogenic / Likely Pathogenic· 170 VUS of 230 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?

0.13LOEUF

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?

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?

LoF OE?0.06 (0.03–0.13)

0≤0.351.4

Missense OE?0.60 (0.55–0.64)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 5 / 79.8Missense obs/exp: 483 / 810.0Syn Z: -1.25

This gene — mechanism propensity

0.4686th %ile

GOF

0.5465th %ile

LOF

0.72top 10%

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

LOFprediction above median · LOEUF 0.13

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

230 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS170

Likely Benign14

Benign9

Pathogenic

Likely Pathogenic

170

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	0	0	1	0	1
VUS	0	161	9	0	170
Likely Benign	0	6	1	7	14
Benign	0	0	7	2	9
Total	1	167	18	9	195

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap MINK1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →