Bleeding and platelet disorders

Gene: MKL1

Green List (high evidence)

Comment on list classification: There are at least 3 unrelated individuals reported in literature with biallelic MKL1 variants associated with immunodeficiency as well thrombocytopenia, neutropenia, and lymphopenia. Hence, this gene should be promoted to Green at the next update.

Created: 12 May 2026, 2:26 p.m. | Last Modified: 12 May 2026, 2:26 p.m.

Panel Version: 4.9

PMID: 40808667 Li et al., 2025
Report of a 3yo girl from China, non-consanguineous parents. Patient presented with early-onset bacterial infections, rashes, and bloody stools, accompanied by neutropenia and thrombocytopenia. WES detected comp het variants p.Q377X & p.C684X in MKL1 (MRTFA). Multiple neutrophil defects demonstrated in patient cells, including increased apoptosis and decreased migration ability.

PMID: 32128589 Sprenkeler et al. 2020
2 sibs with severe early-onset immunodeficiency, lymphopenia and thrombocytopenia. WES revealed homozygous MKL1 variant NM_020831.4:c.1356dup (p.(Val453Argfs*16). 1st sib died from infection in the first weeks of life; younger sister had milder phenotype as she underwent hematopoietic stem cell transplantation at 9 weeks.

PMID: 27479822 Johnson et al., 2016
Patient F37.I reported to harbour variant c.1723G>A, p.Val575Met in MKL1 (classed as VUS). The patient has a mild reduction in platelet count (130×109/L). Not sure on zygosity of this patient.

PMID: 26224645 Record et al., 2015
Female patient with immunodeficiency with recurring severe bacterial infections and mild thrombocytopenia. Parents are second cousins. She was homozygous for p.K723X variant in MKL1. MKL1-deficient neutrophils displayed reduced phagocytosis and almost complete abrogation of migration in vitro

MRTFA is putatively associated with AR ?Immunodeficiency 66, OMIM:618847 in OMIM (accessed 12th May 2026).

Created: 12 May 2026, 1:38 p.m. | Last Modified: 12 May 2026, 2:31 p.m.

Panel Version: 4.9

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Immunodeficiency 66 , OMIM:618847; immunodeficiency 66, MONDO:0030013; neutropenia, MONDO:0001475

Publications

• 26224645
• 27479822
• 32128589
• 40808667

I don't know

I don't know

Comment on list classification: Demoted from Green to Amber. Initial Green gene submitted by one GLH (Carl Fratter Wessex and the West Midlands GLH), subsequently after the GMS Haematology Specialist Test Group webex call 8th March 2019 Patricia Bignell (Wessex and the West Midlands GLH) reviewed gene again and suggested downgrading to Amber (webex 8.03.19 WWMGLH comments v1.doc).

Created: 28 May 2019, 3:36 p.m.

Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber

Created: 28 May 2019, 2:08 p.m.

New HGNC approved gene symbol for MKL1 is MRTFA

Created: 5 Feb 2019, 1:30 p.m.

Initial gene list (Consensus Genes for Panels 17.12.18_Haem_WWMGLH_v3.xlxs) collated by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group. Gene Symbol submitted: MRTFA; Suggested intial gene rating: Green List (high evidence); Are variants in this gene as part of your current diagnostic practice? No; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Phenotypes: N/A; PMID(s): 27479822

Created: 5 Feb 2019, 1:26 p.m.

Green List (high evidence)

Gene rating submitted by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group.

Created: 5 Feb 2019, 11:19 a.m.