Features include always present findings: Low muscle tone (hypotonia) and Ectodermal dysplasia; and very common findings: Recurrent infections. 24 total HPO annotations.

ORAI1 encodes ORAI calcium release-activated calcium modulator 1 (685 aa). Acts as a Ca(2+) sensor that gates two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC) channels. Highest expression in Skin Sun Exposed Lower leg (78.2 TPM) and Skin Not Sun Exposed Suprapubic (72.9 TPM).

Combined immunodeficiency due to ORAI1 deficiency is associated with mutations in the ORAI1 gene on chromosome 12.

The ORAI1 protein participates in STIM1 activation of CRAC, STIM1 oligomerizes, and TRPC1 translocates calcium from the extracellular region to the cytosol pathways.

ORAI1 is classified as a druggable target (Ion Channel, Transcription Factor, and Transporter categories) with score 0.0.

Genetic testing for ORAI1 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for combined immunodeficiency due to ORAI1 deficiency has been reported in the published literature.

Phenotype severity distribution: 2 always present features, 1 very common feature, 5 common features.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

No clinical trials have been registered for combined immunodeficiency due to ORAI1 deficiency.

105 publications have been identified in PubMed for combined immunodeficiency due to ORAI1 deficiency. Research spans Epidemiology / Natural History (34%), Basic Science / Preclinical (21%), and Review / Meta-Analysis (20%).