MAP3K13

protein-coding

mitogen-activated protein kinase kinase kinase 13, the group of Mitogen-activated protein kinase kinase kinases

Gene summary

The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase contains a dual leucine-zipper motif, and has been shown to form dimers/oligomers through its leucine-zipper motif. This kinase can phosphorylate and activate MAPK8/JNK, MAP2K7/MKK7, which suggests a role in the JNK signaling pathway. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004721.5

Inheritance

—

ClinVar variants

U:129B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr3:185,282,941-185,489,094

External References & Databases

Ensembl (ENSG00000073803)

Transcript & Mutation Effects

hg38 • Region Span ~206.2 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 MAP3K13 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 123

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004721.5. 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			1 clinvar	1 clinvar	1 clinvar	3
missense			120 clinvar	7 clinvar		127
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	129	8	1	138

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004721.5	RefSeq	NP_004712.1	13	MANE Select
ENST00000265026.8	Ensembl	ENSP00000265026.3	13	MANE Select
NM_001242314.2	RefSeq	NP_001229243.1	13	Standard
NM_001242317.2	RefSeq	NP_001229246.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MAPK signaling pathway - Homo sapiens (human)
EGF-Core
MAPK Signaling Pathway
Angiopoietin Like Protein 8 Regulatory Pathway
Insulin Signaling

Biological Process

MAPK cascade
activation of MAPKK activity
protein phosphorylation
JNK cascade
activation of JNKK activity

Molecular Function

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

Cellular Component

membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265026
Coding exons: 13
Length: 206157
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125747
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.19	410	555	0.738	0.0000323	6373
Missense (PolyPhen)		127	210.21	0.60414		2316
Synonymous	0.654	195	207	0.942	0.0000126	1856
Loss of Function	5.19	10	49.4	0.203	0.00000311	527

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates the JUN N-terminal pathway through activation of the MAP kinase kinase MAP2K7. Acts synergistically with PRDX3 to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B. {ECO:0000269|PubMed:11726277, ECO:0000269|PubMed:12492477, ECO:0000269|PubMed:9353328}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.331
RVIS EVS: -0.37
RVIS percentile EVS: 28.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.998

Gene Damage Prediction

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