Alt. symbols: AIP1 | HELS52 | NORI1

Approved name: WD repeat domain 1
Alt. names: WD repeatcontaining protein 1 | actininteracting protein 1 | epididymis secretory protein Li 52

Location: 4p16.1: 10068089 - 10116972 (-)
Gene type: protein_coding, 31 transcripts.

Scores: LoFtool: | pLI: 0.99459346 | LOEUF: 0.220

HGNC: 12754

NCBI: 9948, RefSeq: NG_027876.1

Ensembl: ENSG00000071127.18

LRG_ | Status: none

OMIM: 604734

Expression | ProteinAtlas

WDR1 encodes actin-interacting protein-1 (AIP1), which regulates cofilin-mediated actin depolymerization and disassembly protein. It thus plays a role in many actin-dependent processes, such as cytokinesis, chemotactic cell migration, myocardium sarcomere organization, cell shape changes and the establishment of planar cell polarity (PCP) during follicular epithelium development (PMID: 18494608, 15629458, 25792565). It is required for cardiomyocyte growth and maintenance as well as megakaryocyte maturation and platelet shedding.

Predominantly missense mutations are associated with PFITS (periodic fever, immunodeficiency, and thrombocytopenia syndrome) [OMIM: 150550], an autosomal recessive disorder featuring both innate and adaptive immune defects. Common features include early-onset recurrent respiratory and cutaneous infections (involving bacteria and viruses), stomatitis, as well as autoimmune manifestations such as chronic thrombocytopenia, anemia, and periodic fevers, associated with inflammasome activation. Detail ed studies often show impaired neutrophil chemotaxis associated with increased or abnormal F-actin levels, and impaired, normal, or even increased oxidative burst, depending on the stimulus. Because WDR1 also plays crucial roles in lymphocyte development and activation, patients also had quantitative and qualitative B and T cell defects, which, when coupled to their neutrophil defects, result in severe recurrent bacterial and viral infections and impaired wound healing. Moreover, those with autoinflammatory features such as severe mucosal ulcerations and periodic fevers with elevated inflammatory markers appeared to overproduce IL-18 but not IL-1beta, though increased pyrin inflammasome activation and caspase-1 activity is implicated (PMID: 27994071). There is one report of a patient with severe, infantile-onset inflammatory bowel disease harboring compound heterozygous WDR1 variants (maternally inherited p.S549F and paternally inherited p.V424G) who was successfully treated by hematopoietic stem cell transplantation (PMID: 32960541). This boy presented with colitis and severe neutrophilic and eosinophilic duodenitis by 2 months of age, along with oral ulcers, xerosis cutis, and labs notable for CD8+ T cell lymphopenia, peripheral eosinophilia, and elevated IL-18 levels. [Load More]