Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: MKL1

Green List (high evidence)

Comment on list classification: There are now 3 unrelated individuals with biallelic MKL1 variants and immunodeficiency due to neutrophil defects. Hence, this gene should be promoted to Green at the next update.

Created: 12 May 2026, 1:32 p.m. | Last Modified: 12 May 2026, 1:34 p.m.

Panel Version: 9.4

3rd case:
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.

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

Created: 12 May 2026, 1:26 p.m. | Last Modified: 12 May 2026, 1:36 p.m.

Panel Version: 9.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Immunodeficiency 66 , OMIM:618847

Publications

• 40808667

Comment on list classification: Promoted from Red to Amber based on expert review and additional of second case.

Created: 17 Apr 2020, 11:34 a.m. | Last Modified: 17 Apr 2020, 11:34 a.m.

Panel Version: 2.101

I don't know

Second family reported.

Created: 11 Apr 2020, 4:01 a.m. | Last Modified: 11 Apr 2020, 4:01 a.m.

Panel Version: 2.51

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neutropaenia with combined immune deficiency

Publications

• 32128589
• 26224645

Red List (low evidence)

single case

Created: 29 Jun 2018, 9:45 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
susceptibility to severe bacterial infection

Publications

• 26224645

Red List (low evidence)

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): MKL1 .PanelApp HGNC gene symbol check: MKL1 . IUIS Disease: Neutropenia with combined immune deficiency due to MKL1 deficiency . IUIS Inheritance: AR .T cells: Very low, .B cells: N/A, .IUIS Other affected cells: N + M +L + NK. IUIS Associated features: Mild thrombocytopenia. IUIS Major category: Congenital defects of phagocyte number or function. IUIS Subcategory: Defects of Motility

Created: 2 Jul 2018, 10:35 a.m.

added new gene name tag - HGNC approved gene name is MRTFA

Created: 27 Jun 2018, 8:56 a.m.