MRTFA

Chr 22AR

myocardin related transcription factor A

NCBI Gene: 57591ENSG00000196588UniProt: Q969V6

Transcription coactivator that associates with the serum response factor (SRF) transcription factor to control expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration (PubMed:26224645). The SRF-MRTFA complex activity responds to Rho GTPase-induced changes in cellular globular actin (G-actin) concentration, thereby coupling cytoskeletal gene expression to cytoskeletal dynamics. MRTFA binds G-actin via its RPEL repeats, regulating activity of the MRTFA-SRF complex. Activity is also regulated by filamentous actin (F-actin) in the nucleus

Primary Disease Associations & Inheritance

?Immunodeficiency 66MIM #618847
AR
961
ClinVar variants
4
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MRTFA
⚡
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
4 Pathogenic / Likely Pathogenic· 362 VUS of 961 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.
0.26LOEUF
pLI 0.998
Z-score 4.89
OE 0.11 (0.06–0.26)
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.
0.02Z-score
OE missense 1.00 (0.93–1.07)
528 obs / 529.2 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.0.11 (0.06–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.93–1.07)
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.1.23
0≤1.21.6
LoF obs/exp: 4 / 35.4Missense obs/exp: 528 / 529.2Syn Z: -2.82

ClinVar Variant Classifications

961 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic1
VUS362
Likely Benign209
Benign5
Conflicting5
3
Pathogenic
1
Likely Pathogenic
362
VUS
209
Likely Benign
5
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
3
0
3
Likely Pathogenic
0
0
1
0
1
VUS
1
323
36
2
362
Likely Benign
1
7
55
146
209
Benign
0
0
3
2
5
Conflicting
—5
Total233098150585

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

View in ClinVar →

Protein Context — Lollipop Plot

MRTFA · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Immunodeficiency 66

MIM #618847

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Methyltransferase-like 3-catalysed N6-methyladenosine methylation facilitates the contribution of vascular smooth muscle cells to atherosclerosis.
Dong Z et al.·Cardiovasc Res
2025
Novel compound heterozygous MRTFA gene variants cause multiple dysfunctions of neutrophils and autoinflammation.
Li W et al.·Pediatr Allergy Immunol
2025Case report
Pathologic, cytogenetic, and molecular features of acute myeloid leukemia with megakaryocytic differentiation: A report from the Children's Oncology Group.
Chisholm KM et al.·Pediatr Blood Cancer
2023
SRF/MRTF-A and liver cirrhosis: Pathologic associations.
Al-Hetty HRAK et al.·J Dig Dis
2022Review
Nuclear translocation of MRTFA in MCF7 breast cancer cells shifts ERα nuclear/genomic to extra-nuclear/non genomic actions.
Jehanno C et al.·Mol Cell Endocrinol
2021
Autoimmune cytopenias in inborn errors of immunity: associations with monogenic mutations and immunologic parameters.
Sağun F et al.·BMC Immunol
2025
Hypoglycemia induces brain metabolic reprogramming and neurodegeneration via serum response factor and myocardin-related transcription factor-A.
Jang M et al.·Signal Transduct Target Ther
2025
Thymosin ß4 and MRTF-A mitigate vessel regression despite cardiovascular risk factors.
Kupatt C et al.·Int Immunopharmacol
2023Review
Synergistic activation of genes promoting invasiveness by dual deprivation in oxygen and nutrients.
Jehanno C et al.·Int J Exp Pathol
2023
Discovery of GS-2278, a Potent and Selective LPAR1 Antagonist for the Treatment of Idiopathic Pulmonary Fibrosis.
Tang DT et al.·J Med Chem
2025
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