MAP3K7

Chr 6AD

mitogen-activated protein kinase kinase kinase 7

Also known as: CSCF, FMD2, MEKK7, TAK1, TGF1a

NCBI Gene: 6885ENSG00000135341UniProt: O43318

The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Cardiospondylocarpofacial syndromeMIM #157800
AD
Frontometaphyseal dysplasia 2MIM #617137
AD
405
ClinVar variants
38
Pathogenic / LP
—
pLI score
0
Active trials
Clinical Summary— MAP3K7
📋
ClinVar Variants
38 Pathogenic / Likely Pathogenic· 194 VUS of 405 total submissions
Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 502

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

405 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic12
VUS194
Likely Benign112
Benign45
Conflicting16
26
Pathogenic
12
Likely Pathogenic
194
VUS
112
Likely Benign
45
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
10
16
0
26
Likely Pathogenic
1
9
2
0
12
VUS
6
145
39
4
194
Likely Benign
0
8
58
46
112
Benign
0
1
41
3
45
Conflicting
—16
Total717315653405

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MAP3K7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MAP3K7-related frontometaphyseal dysplasia

strong
ADUndeterminedAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cardiospondylocarpofacial syndrome

MIM #157800

Molecular basis of disorder known

Autosomal dominant

Frontometaphyseal dysplasia 2

MIM #617137

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — MAP3K7
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genome-wide association analysis provides insights into the molecular etiology of dilated cardiomyopathy.
Zheng SL et al.·Nat Genet
2024
The MAP3K7 gene: Further delineation of clinical characteristics and genotype/phenotype correlations.
van Woerden GM et al.·Hum Mutat
2022
MAP3K kinases and kidney injury.
Cuarental L et al.·Nefrologia (Engl Ed)
2019Review
Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management.
Shi Y et al.·Urol Oncol
2024Review
A novel variant in MAP3K7 associated with an expanded cardiospondylocarpofacial syndrome phenotype.
AbuBakr F et al.·Cold Spring Harb Mol Case Stud
2020Case report
Coordinate loss of MAP3K7 and CHD1 promotes aggressive prostate cancer.
Rodrigues LU et al.·Cancer Res
2015
Expanding the phenotypic spectrum of cardiospondylocarpofacial syndrome: From a detailed clinical and radiological observation of a boy with a novel missense variant in MAP3K7.
Minatogawa M et al.·Am J Med Genet A
2022Case report
MAP3K7 is recurrently deleted in pediatric T-lymphoblastic leukemia and affects cell proliferation independently of NF-κB.
Cordas Dos Santos DM et al.·BMC Cancer
2018Clinical trial
MAP3K7 Loss Drives Enhanced Androgen Signaling and Independently Confers Risk of Recurrence in Prostate Cancer with Joint Loss of CHD1.
Jillson LK et al.·Mol Cancer Res
2021
Insights into the molecular pathogenesis of cardiospondylocarpofacial syndrome: MAP3K7 c.737-7A > G variant alters the TGFβ-mediated α-SMA cytoskeleton assembly and autophagy.
Micale L et al.·Biochim Biophys Acta Mol Basis Dis
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Exosomal miR-10b derived from protocatechuic acid-treated efferocytic macrophages inhibits endothelial inflammation by targeting MAP3K7/β-TrCP/NF-κB signaling pathway.
Li Q et al.·Phytomedicine
2026
CRISPR screens in the context of immune selection identify CHD1 and MAP3K7 as mediators of cancer immunotherapy resistance.
Watterson A et al.·Cell Rep Med
2026🔓 Open Access
Exosomal tpi-miR-10a-5p from T. pisiformis cysticerci regulates the expression of inflammatory factors in rabbits by targeting MAP3K7.
Pu G et al.·Vet Parasitol
2025
Neonatal dilated cardiomyopathy and cardiospondylocarpofacial syndrome linked to a novel MAP3K7 gene mutation.
Das BB et al.·Ann Pediatr Cardiol
2025🔓 Open Access
Silencing Map3k7 suppresses pyroptosis to alleviate bronchopulmonary dysplasia through inhibiting the TGF-β1/Smad3 pathway.
Zhen H et al.·Gen Physiol Biophys
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools