Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: MYB

Green List (high evidence)

Comment on list classification: There are two unrelated patients with heterozygous SNVs in Myb gene and functional evidence including mouse models available from peer-reviewed published scientific literature in support of the association of Myb with combined immunodeficiency. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 30 Jul 2026, 3:59 p.m. | Last Modified: 30 Jul 2026, 3:59 p.m.

Panel Version: 9.41

PMID:27577878 (2016) reported a cohort of patients with primary immunodeficiency diseases from 278 families from 22 countries investigated using whole-exome sequencing, of which one patient (8 year-old female) with immunodeficiency, progressive bone marrow failure, short stature and dysmorphic facial features were identified with a heterozygous 3.4Mb deletion on chromosome 6 including Myb gene.

PMID:36168523 (2022) reported two patients presenting with a combined deficiency phenotype ((B-cell lymphocytopenia, hypogammaglobulinemia) that progressed into severe bone marrow dysfunction. Patient 1 (a 22-year old male of Dutch descent) additionally showed telomere shortening and Case 2 ( of French-Canadian descent) developed autoimmune-like features (polyarthritis, granulomatous dermatitis). They both were identified with de novo heterozygous variants in DNA-binding domain of MYB gene using trio exome sequnecing (patient 1: c.545A>G/ p.Lys182Arg; patient 2: c.383A>G/ p.Lys128Arg). Functional evidence is available for patient 1 (T-cell phenotyping, RT-PCR, flow cytometry) showing altered Zeb2/c-Myb/Tcf7 expression, particularly in CD8+ T cells.

There is also evidence available from mice models - Homozygous null variants of MYB in mice were shown to be lethal. But, heterozygous, temporal and local null models of the DNA-binding domain exon in mice and human cell lines have shown that its product, the c-Myb transcription factor, is crucial for pro- and pre-B cell differentiation by controlling the expression of interleukin-7 receptor-α, and recombinase activating gene (Rag) and the initiation of survival signals (PMIDs: 20130238 (2010) & 29654210 (2019)).

This gene has not yet been associated with immunodeficiency phenotype in OMIM (last accessed 30 July 2026).

Created: 30 Jul 2026, 3:56 p.m. | Last Modified: 30 Jul 2026, 3:56 p.m.

Panel Version: 9.37

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
combined immunodeficiency, MONDO:0015131

Publications

• 20130238
• 27577878
• 29654210
• 36168523

Green List (high evidence)

Aaron Boothby et al. presented ten heterozygous germline MYB variants in seven families and four unrelated singletons. The variants segregated with autoimmune cytopenias, including Evans syndrome, in three five-generation pedigrees. In our cohort of 41 carriers, 22 were affected by autoimmune cytopenias, while one had isolated B cell lymphopenia and neutropenia.

https://rupress.org/jhi/article/2/CIS2026/eCIS2026abstract.16/281957/MYB-Haploinsufficiency-Causes-Familial-Autoimmune
Sources: Literature

Created: 17 Jun 2026, 1:58 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Evans syndrome; Neutropenia; Autoimmune cytopenias; B cell lymphopenia