MAP3K19

protein-coding

mitogen-activated protein kinase kinase kinase 19, the group of Mitogen-activated protein kinase kinase kinases

Gene summary

Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in MAPK cascade. [provided by Alliance of Genome Resources, Apr 2025]

Previous symbols:

YSK4

MANE transcript

NM_025052.5

Inheritance

—

ClinVar variants

U:145B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr2:134,964,485-135,047,468

External References & Databases

Ensembl (ENSG00000176601)

Transcript & Mutation Effects

hg38 • Region Span ~83.0 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 MAP3K19 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 149

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025052.5. 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
missense			141 clinvar	11 clinvar		152
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	145	12	0	157

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025052.5	RefSeq	NP_079328.3	10	MANE Select
ENST00000392915.7	Ensembl	ENSP00000376647.2	10	MANE Select
NM_001018044.3	RefSeq	NP_001018054.1	8	Standard
NM_001018046.3	RefSeq	NP_001018056.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

signal transduction by protein phosphorylation
stress-activated protein kinase signaling cascade
activation of protein kinase activity

Molecular Function

protein serine/threonine kinase activity
ATP binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375845
Coding exons: 10
Length: 82978
Individuals with no LoFs: 125633
Homozygous LoFs: 0
Heterozygous LoFs: 115
Defined: 125748
p: 0.000457

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.760	619	675	0.918	0.0000331	8851
Missense (PolyPhen)		129	136.89	0.94239		1807
Synonymous	-0.0235	238	238	1.00	0.0000120	2437
Loss of Function	1.43	40	51.0	0.784	0.00000276	667

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0027	0.0027	notable
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0015	0.0015	notable
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0.00030	0.00029	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0686

Intolerance Scores

RVIS EVS: 2.05
RVIS percentile EVS: 97.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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