MINK1

protein-coding

misshapen like kinase 1, the group of Armadillo like helical domain containing|STRIPAK complex

Gene summary

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]

MANE transcript

NM_153827.5

Inheritance

—

ClinVar variants

U:179B:15

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr17:4,833,340-4,898,061

External References & Databases

Ensembl (ENSG00000141503)

Transcript & Mutation Effects

hg38 • Region Span ~64.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MINK1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 166

not providedTotal: 15

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153827.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	7 clinvar	2 clinvar	11
missense			170 clinvar	6 clinvar		176
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	179	13	2	194

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 73 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153827.5	RefSeq	NP_722549.2	32	MANE Select
ENST00000355280.11	Ensembl	ENSP00000347427.6	32	MANE Select
NM_001024937.4	RefSeq	NP_001020108.1	32	Standard
NM_001321236.2	RefSeq	NP_001308165.1	29	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGF-Core
Oxidative Stress Induced Senescence
Angiopoietin Like Protein 8 Regulatory Pathway
Insulin Signaling
Oxidative Stress Induced Senescence

Biological Process

MAPK cascade
regulation of cell-matrix adhesion
protein phosphorylation
JNK cascade
chemical synaptic transmission

Molecular Function

protein kinase activity
protein serine/threonine kinase activity
protein binding
ATP binding

Cellular Component

cytoplasm
Golgi apparatus
cytosol
postsynaptic density
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355280
Coding exons: 32
Length: 64674
Individuals with no LoFs: 124733
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 124743
p: 0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.08	483	810	0.596	0.0000525	8545
Missense (PolyPhen)		132	281.39	0.4691		2883
Synonymous	-1.25	354	325	1.09	0.0000214	2590
Loss of Function	7.76	5	79.8	0.0627	0.00000474	815

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000064	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000035	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking. Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons. Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates: TANC1 upon stimulation by RAP2A, MBP and SMAD1. Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1.;

Recessive Scores

pRec: 0.139

Intolerance Scores

LoFtool: 0.404
RVIS EVS: -1.46
RVIS percentile EVS: 3.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.986

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium