MRTFA

myocardin related transcription factor A, the group of Myocardin family

Basic information

Region (hg38): 22:40410281-40636719

Previous symbols: [ "MKL1" ]

Links

ENSG00000196588 ∙ NCBI:57591 ∙ OMIM:606078 ∙ HGNC:14334 ∙ Uniprot:Q969V6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 66 (Limited), mode of inheritance: Unknown
• immunodeficiency 66 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 66	AR	Allergy/Immunology/Infectious	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	Allergy/Immunology/Infectious	26224645

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MRTFA gene.

• not_provided (734 variants)
• not_specified (187 variants)
• MRTFA-related_disorder (28 variants)
• Immunodeficiency_66 (11 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MRTFA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020831.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	224	6	233
missense			416	28	5	449
nonsense	1		3			4
start loss						0
frameshift			4			4
splice donor/acceptor (+/-2bp)						0
Total	1	0	426	252	11

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MRTFA	protein_coding	protein_coding	ENST00000355630	12	226422

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00232	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0178	528	529	0.998	0.0000313	5922
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000339	0.0000339
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000445	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000338	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.204
• hipred: Y
• hipred_score: 0.722
• ghis: 0.529

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Mrtfa
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• 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
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol
• Molecular function: transcription coactivator activity;actin binding;actin monomer binding;protein binding;leucine zipper domain binding