ORAI3

Chr 16

ORAI calcium release-activated calcium modulator 3

Also known as: TMEM142C

NCBI Gene: 93129ENSG00000175938UniProt: Q9BRQ5

Enables store-operated calcium channel activity. Involved in store-operated calcium entry. Located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

67
ClinVar variants
14
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— ORAI3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 51 VUS of 67 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.23LOEUF
pLI 0.034
Z-score 1.20
OE 0.48 (0.22–1.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.07Z-score
OE missense 0.98 (0.86–1.12)
160 obs / 162.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.48 (0.22–1.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.86–1.12)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 3 / 6.3Missense obs/exp: 160 / 162.7Syn Z: -0.37

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic3
VUS51
Likely Benign2
11
Pathogenic
3
Likely Pathogenic
51
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
3
0
3
VUS
0
43
8
0
51
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total04522067

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ORAI3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The neuro-immune oncology axis.
Vanden Abeele F et al.·Cancer Lett
2025Review
Orai3 Calcium Channel Contributes to Oral/Oropharyngeal Cancer Stemness through the Elevation of ID1 Expression.
Nguyen A et al.·Cells
2023
ALOX5 drives the pyroptosis of CD4(+) T cells and tissue inflammation in rheumatoid arthritis.
Cai H et al.·Sci Signal
2024
Targeting Stim and Orai Proteins as an Alternative Approach in Anticancer Therapy.
Moccia F et al.·Curr Med Chem
2016Review
ORAI3 Modulates Oral Squamous Cell Carcinoma Metastasis Through the Ca(2+)/Calmodulin/Calcineurin/ETV4 Signaling Pathway.
Chen S et al.·FASEB J
2025
Reduced store operated calcium entry contributes to autophagy mediated escape of prostate cancer to oxaliplatin treatment.
Kannancheri Puthooru D et al.·Biochim Biophys Acta Mol Cell Res
2025
Modulation of intracellular calcium signaling by microRNA-34a-5p.
Diener C et al.·Cell Death Dis
2018
Regulation of lymphocyte function by ORAI and STIM proteins in infection and autoimmunity.
Shaw PJ et al.·J Physiol
2012Review
Enhanced Contribution of Orai Channels to Contractility of Human Penile Smooth Muscle in Erectile Dysfunction.
Sevilleja-Ortiz A et al.·J Sex Med
2020
Blocking Store-Operated Ca(2+) Entry to Protect HL-1 Cardiomyocytes from Epirubicin-Induced Cardiotoxicity.
Liu X et al.·Cells
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools