ORAI3

protein-coding

ORAI calcium release-activated calcium modulator 3, the group of ORAI calcium release-activated calcium modulators

Gene summary

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

Previous symbols:

TMEM142C

MANE transcript

NM_152288.3

Inheritance

—

ClinVar variants

U:45B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr16:30,949,068-30,956,461

External References & Databases

Ensembl (ENSG00000175938)

Transcript & Mutation Effects

hg38 • Region Span ~7.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ORAI3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 45

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152288.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			43 clinvar	2 clinvar		45
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	45	2	0	47

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152288.3	RefSeq	NP_689501.1	2	MANE Select
ENST00000318663.5	Ensembl	ENSP00000322249.4	2	MANE Select
ENST00000562699.1	Ensembl	ENSP00000457025.1	2	Standard
ENST00000562699.2	Ensembl	ENSP00000457025.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Calcium signaling pathway - Homo sapiens (human)

Biological Process

store-operated calcium entry
calcium ion transmembrane transport

Molecular Function

protein binding
store-operated calcium channel activity

Cellular Component

membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000318663
Coding exons: 2
Length: 7396
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125748
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0744	160	163	0.984	0.00000875	1856
Missense (PolyPhen)		74	81.944	0.90306		983
Synonymous	-0.370	77	73.0	1.06	0.00000404	673
Loss of Function	1.20	3	6.25	0.480	2.69e-7	72

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0017	0.0017	notable
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00010	0.000097	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Key regulator or component of store-operated Ca(2+) channel and transcription factor NFAT nuclear import. {ECO:0000250}.;

Recessive Scores

pRec: 0.0977

Intolerance Scores

RVIS EVS: -0.34
RVIS percentile EVS: 30.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.495

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium