MRTFB

Chr 16

myocardin related transcription factor B

Also known as: MKL2, MRTF-B, NPD001

NCBI Gene: 57496ENSG00000186260UniProt: Q9ULH7OMIM: 609463

The MRTFB protein acts as a transcriptional coactivator of serum response factor (SRF) and is required for skeletal myogenic differentiation. Mutations cause autosomal dominant developmental and epileptic encephalopathy, affecting neurological development and muscle function. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.17), indicating that complete loss of function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 0.17
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 unique Pathogenic / Likely Pathogenic· 162 VUS of 208 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
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
0.52Z-score
OE missense 0.94 (0.88–1.01)
548 obs / 583.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.03–0.17)
0≤0.351.4
Missense OE0.94 (0.88–1.01)
0≤0.61.4
Synonymous OE1.12
0≤1.21.6
LoF obs/exp: 3 / 45.6Missense obs/exp: 548 / 583.6Syn Z: -1.40
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedMRTFB-related neurodevelopmental disorderGOFAD
DN
0.3097th %ile
GOF
0.2597th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

208 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS162
Likely Benign15
Benign4
16
Pathogenic
1
Likely Pathogenic
162
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
149
11
1
162
Likely Benign
0
9
1
5
15
Benign
0
2
0
2
4
Total1162269198

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
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
Expression of smooth muscle cell markers and co-activators in calcified aortic valves.
Latif N et al.·Eur Heart J
2015
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients