MAP3K15

protein-coding

mitogen-activated protein kinase kinase kinase 15, the group of Mitogen-activated protein kinase kinase kinases

Gene summary

The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAPK) family. These family members function in a protein kinase signal transduction cascade, where an activated MAPK kinase kinase (MAP3K) phosphorylates and activates a specific MAPK kinase (MAP2K), which then activates a specific MAPK. This MAP3K protein plays an essential role in apoptotic cell death triggered by cellular stresses. [provided by RefSeq, Jul 2010]

MANE transcript

NM_001001671.4

Inheritance

—

ClinVar variants

U:308B:45

Top phenotype

MAP3K15-related disorder

gnomAD constraint

pLI —, LoF o/e 1.05

Max pathogenic AF

—

Genomic locus

chrX:19,360,056-19,515,508

External References & Databases

Ensembl (ENSG00000180815)

Transcript & Mutation Effects

hg38 • Region Span ~155.5 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 MAP3K15 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 221

MAP3K15-related disorderTotal: 40

not providedTotal: 22

Pyruvate dehydrogenase E1-alpha deficiencyTotal: 15

Neurodevelopmental disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001001671.4. 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			14 clinvar	18 clinvar	4 clinvar	36
missense			246 clinvar	13 clinvar	8 clinvar	267
nonsense			13 clinvar			13
start loss						0
frameshift			3 clinvar	1 clinvar		4
splice donor/acceptor (+/-2bp)			32 clinvar	1 clinvar		33
Total	0	0	308	33	12	353

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001001671.4	RefSeq	NP_001001671.3	29	MANE Select
ENST00000338883.9	Ensembl	ENSP00000345629.4	29	MANE Select
ENST00000359173.7	Ensembl	ENSP00000352093.4	7	Standard
ENST00000927252.1	Ensembl	ENSP00000597311.1	29	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

MAPK cascade
activation of MAPKK activity

Molecular Function

protein kinase activity
MAP kinase kinase kinase activity
ATP binding
metal ion binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000338883
Coding exons: 29
Length: 155206
Individuals with no LoFs: 125588
Homozygous LoFs: 51
Heterozygous LoFs: 109
Defined: 125748
p: 0.000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.783	523	475	1.10	0.0000381	8531
Missense (PolyPhen)		139	147.53	0.94216		2838
Synonymous	-1.53	219	192	1.14	0.0000164	2514
Loss of Function	-0.299	47	44.8	1.05	0.00000343	801

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00071	0.00049	rare
Latino/Admixed American	0.00033	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0021	0.0016	notable
Finnish	0.00018	0.000092	rare
European (Non-Finnish)	0.00080	0.00055	rare
South Asian	0.0024	0.0013	notable
Other	0.0018	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function in a signal transduction pathway that is activated by various cell stresses and leads to apoptosis. {ECO:0000269|PubMed:20362554}.;

Recessive Scores

pRec: 0.0939

Essentials

Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.563

Gene Damage Prediction

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