MRTFA
protein-codingmyocardin related transcription factor A, the group of Myocardin family
Gene summary
The protein encoded by this gene interacts with the transcription factor myocardin, a key regulator of smooth muscle cell differentiation. The encoded protein is predominantly nuclear and may help transduce signals from the cytoskeleton to the nucleus. This gene is involved in a specific translocation event that creates a fusion of this gene and the RNA-binding motif protein-15 gene. This translocation has been associated with acute megakaryocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
- MKL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~226.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0030013
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0030013
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0030013
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious
Intervention: Allergy/Immunology/Infectious
Rationale: An individual has been described with severe, early-onset, and recurrent infections, as well as reaction related to BCG vaccine, and and awareness and prompt and aggressive treatment of infections and related sequelae may be beneficial
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MRTFA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020831.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 263 | 2 | 266 | ||
| missense | 485 | 37 | 3 | 525 | ||
| nonsense | 1 | 5 | 6 | |||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 1 | 0 | 502 | 300 | 5 | 808 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065882.2 | 13 | MANE Select | |
| Ensembl | ENSP00000347847.5 | 13 | MANE Select | |
| RefSeq | NP_001269589.1 | 12 | Standard | |
| RefSeq | NP_001269590.2 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- positive regulation of transcription via serum response element binding
- actin cytoskeleton organization
- positive regulation of transcription by RNA polymerase II
- smooth muscle cell differentiation
Molecular Function
- transcription coactivator activity
- actin binding
- actin monomer binding
- protein binding
- leucine zipper domain binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000355630
- Coding exons
- 12
- Length
- 226422
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125748
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0178 | 528 | 529 | 0.998 | 0.0000313 | 5922 |
| Missense (PolyPhen) | 244 | 266.63 | 0.91512 | 3002 | ||
| Synonymous | -2.82 | 305 | 248 | 1.23 | 0.0000165 | 2014 |
| Loss of Function | 4.89 | 4 | 35.4 | 0.113 | 0.00000191 | 393 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000034 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 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. 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. {ECO:0000250|UniProtKB:Q8K4J6}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving MRTFA may be a cause of acute megakaryoblastic leukemia. Translocation t(1;22)(p13;q13) with RBM15 (PubMed:11431691, PubMed:11344311). Although both reciprocal fusion transcripts are detected in acute megakaryoblastic leukemia (AMKL, FAB-M7), the RBM15-MRTFA chimeric protein has all the putative functional domains encoded by each gene and is the candidate oncogene (PubMed:11431691, PubMed:11344311). {ECO:0000269|PubMed:11344311, ECO:0000269|PubMed:11431691}.;
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- RVIS EVS
- -0.53
- RVIS percentile EVS
- 20.91
Essentials
- Essential (gene trap)
- N