MAP3K20

Chr 2

mitogen-activated protein kinase kinase kinase 20

Also known as: AZK, CNM6, MLK7, MLT, MLTK, MLTKalpha, MLTKbeta, MRK

This gene is a member of the MAPKKK family of signal transduction molecules and encodes a protein with an N-terminal kinase catalytic domain, followed by a leucine zipper motif and a sterile-alpha motif (SAM). This magnesium-binding protein forms homodimers and is located in the cytoplasm. The protein mediates gamma radiation signaling leading to cell cycle arrest and activity of this protein plays a role in cell cycle checkpoint regulation in cells. The protein also has pro-apoptotic activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…
LOFmechanismLOEUF 0.68
Clinical SummaryMAP3K20
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Gene-Disease Validity (ClinGen)
myopathy, centronuclear, 6, with fiber-type disproportion · ARStrong

Strong evidence — appropriate for clinical testing

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 151 VUS of 481 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.68LOEUF
pLI 0.000
Z-score 3.26
OE 0.47 (0.330.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.51Z-score
OE missense 0.79 (0.720.87)
335 obs / 422.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.47 (0.330.68)
00.351.4
Missense OE?0.79 (0.720.87)
00.61.4
Synonymous OE?1.00
01.21.6
LoF obs/exp: 21 / 44.4Missense obs/exp: 335 / 422.1Syn Z: -0.02
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateMAP3K20-related centronuclear myopathyLOFAR
moderateMAP3K20-related split-foot malformation with mesoaxial polydactylyLOFAR
limitedMAP3K20-related ectodermal dysplasia with craniosynostosis, sensorineural hearing loss, and limb anomaliesOTHERAD

This gene — mechanism propensity

DN
0.6161th %ile
GOF
0.5857th %ile
LOF
0.3940th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

481 submitted variants in ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic3
VUS151
Likely Benign233
Benign48
Conflicting4
12
Pathogenic
3
Likely Pathogenic
151
VUS
233
Likely Benign
48
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
1
3
0
12
Likely Pathogenic
2
1
0
0
3
VUS
4
140
7
0
151
Likely Benign
0
8
119
106
233
Benign
0
9
33
6
48
Conflicting
4
Total14159162112451

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap MAP3K20 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

MAP3K20 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →