MRTFB

Chr 16

myocardin related transcription factor B

Also known as: MKL2, MRTF-B, NPD001

NCBI Gene: 57496ENSG00000186260UniProt: Q9ULH7

Enables transcription coactivator activity. Involved in positive regulation of miRNA transcription; positive regulation of striated muscle tissue development; and positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be active in several cellular components, including glutamatergic synapse; postsynapse; and presynapse. [provided by Alliance of Genome Resources, Apr 2025]

195
ClinVar variants
17
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MRTFB
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 159 VUS of 195 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.17LOEUF
pLI 1.000
Z-score 5.85
OE 0.07 (0.03–0.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.52Z-score
OE missense 0.94 (0.88–1.01)
548 obs / 583.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.03–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.88–1.01)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 3 / 45.6Missense obs/exp: 548 / 583.6Syn Z: -1.40

ClinVar Variant Classifications

195 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS159
Likely Benign15
Benign4
16
Pathogenic
1
Likely Pathogenic
159
VUS
15
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
13
1
16
Likely Pathogenic
0
0
1
0
1
VUS
1
146
12
0
159
Likely Benign
0
9
1
5
15
Benign
0
2
0
2
4
Total1159278195

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

View in ClinVar →

Protein Context — Lollipop Plot

MRTFB · protein map & ClinVar variants

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

Gene2Phenotype Curations

MRTFB-related neurodevelopmental disorder

limited
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variant

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
De novo variants in MRTFB have gain-of-function activity in Drosophila and are associated with a novel neurodevelopmental phenotype with dysmorphic features.
Andrews JC et al.·Genet Med
2023
RREB1::MRTFB fusion-positive extra-glossal mesenchymal neoplasms: A series of five cases expanding their anatomic distribution and highlighting significant morphological and phenotypic diversity.
Agaimy A et al.·Genes Chromosomes Cancer
2023Cohort
KLF15 maintains contractile phenotype of vascular smooth muscle cells and prevents thoracic aortic dissection by interacting with MRTFB.
Fang G et al.·J Biol Chem
2024
Novel CRTC1::MRTFB(MKL2) Gene Fusion Detected in Myxoid Mesenchymal Neoplasms With Myogenic Differentiation Involving Bone and Soft Tissues.
Warmke LM et al.·Mod Pathol
2024Case report
MRTF-dependent cytoskeletal dynamics drive efficient cell cycle progression.
Nielsen JC et al.·J Cell Sci
2025
Brain-derived neurotrophic factor (BDNF) downregulates mRNA levels of suppressor of cancer cell invasion (SCAI) variants in cortical neurons.
Ihara D et al.·Genes Cells
2024
Myocardin Is Involved in Mesothelial-Mesenchymal Transition of Human Pleural Mesothelial Cells.
Tucker T et al.·Am J Respir Cell Mol Biol
2019
Expression of smooth muscle cell markers and co-activators in calcified aortic valves.
Latif N et al.·Eur Heart J
2015
Development of Targeted siRNA Nanocomplexes to Prevent Fibrosis in Experimental Glaucoma Filtration Surgery.
Fernando O et al.·Mol Ther
2018
Control of phenotypic plasticity of smooth muscle cells by bone morphogenetic protein signaling through the myocardin-related transcription factors.
Lagna G et al.·J Biol Chem
2007
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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