MAP3K10

protein-coding

mitogen-activated protein kinase kinase kinase 10, the group of Mitogen-activated protein kinase kinase kinases

Gene summary

The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase has been shown to activate MAPK8/JNK and MKK4/SEK1, and this kinase itself can be phoshorylated, and thus activated by JNK kinases. This kinase functions preferentially on the JNK signaling pathway, and is reported to be involved in nerve growth factor (NGF) induced neuronal apoptosis. [provided by RefSeq, Jul 2008]

Previous symbols:

MLK2

MANE transcript

NM_002446.4

Inheritance

—

ClinVar variants

U:145B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr19:40,191,426-40,215,575

External References & Databases

Ensembl (ENSG00000130758)

Transcript & Mutation Effects

hg38 • Region Span ~24.1 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 MAP3K10 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 141

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002446.4. 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			1 clinvar	1 clinvar		2
missense			140 clinvar	4 clinvar		144
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	145	5	0	150

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002446.4	RefSeq	NP_002437.2	10	MANE Select
ENST00000253055.8	Ensembl	ENSP00000253055.2	10	MANE Select
ENST00000593502.5	Ensembl	ENSP00000473021.1	3	Standard
ENST00000594951.1	Ensembl	ENSP00000471116.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGF-Core
Angiopoietin Like Protein 8 Regulatory Pathway
Insulin Signaling
IL-7 signaling
JAK STAT pathway and regulation

Biological Process

MAPK cascade
apoptotic process
signal transduction
smoothened signaling pathway
JNK cascade

Molecular Function

transcription corepressor activity
protein kinase activity
protein serine/threonine kinase activity
JUN kinase kinase kinase activity
ATP binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000253055
Coding exons: 10
Length: 23832
Individuals with no LoFs: 125697
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125735
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.95	367	564	0.650	0.0000390	5952
Missense (PolyPhen)		104	217.36	0.47847		2161
Synonymous	1.55	215	246	0.875	0.0000167	2075
Loss of Function	3.95	6	29.0	0.207	0.00000134	343

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00053	0.00052	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00015	0.00014	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates the JUN N-terminal pathway. {ECO:0000250}.;

Recessive Scores

pRec: 0.155

Intolerance Scores

LoFtool: 0.176
RVIS EVS: -1.13
RVIS percentile EVS: 6.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.982

Gene Damage Prediction

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