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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
STIM1
stromal interaction molecule 1
Chromosome 11 Β· 11p15.4
NCBI Gene: 6786Ensembl: ENSG00000167323.13HGNC: HGNC:11386UniProt: A0A8V8TMF0
552PubMed Papers
23Diseases
0Drugs
37Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Highly Studied
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protease bindingcalcium channel regulator activitycalcium ion bindingprotein bindingmyopathy, tubular aggregate, 1combined immunodeficiency due to STIM1 deficiencyStormorken syndrometubular aggregate myopathy
✦AI Summary

STIM1 is a calcium sensor protein anchored in the endoplasmic reticulum (ER) membrane that regulates store-operated calcium entry (SOCE), a critical calcium influx pathway in cells 1. Upon depletion of intracellular calcium stores, STIM1 translocates to the plasma membrane where it directly binds to and activates calcium release-activated calcium (CRAC) channels, particularly the pore-forming subunit ORAI1, to mediate sustained calcium influx 12. This STIM1-ORAI1 interaction occurs within specialized membrane microdomains where the ER and plasma membrane come into close apposition 3. STIM1 also regulates transient receptor potential canonical (TRPC) channels, though TRPC activation can occur independently of STIM1 4. Loss-of-function mutations in STIM1 cause CRAC channelopathies characterized by abolished calcium entry and clinical manifestations including immunodeficiency, congenital myopathy, and anhydrotic ectodermal dysplasia 1. Beyond immune function, dysregulated STIM1-mediated calcium signaling contributes to stroke pathogenesis and cancer progression, where elevated STIM1 expression promotes tumor metastasis through effects on invadopodia formation, angiogenesis, and inflammatory responses 56. STIM1 protein stability is regulated by ubiquitination, providing potential therapeutic targets for conditions involving aberrant STIM1 signaling 7.

Sources cited
1
STIM1 is an ER calcium sensor that activates CRAC channels upon store depletion; mutations cause immunodeficiency, congenital myopathy, and ectodermal dysplasia
PMID: 20111871
2
STIM1 activation of ORAI1 triggers calcium-dependent gene transcription and T-cell activation
PMID: 30530091
3
STIM1-ORAI1 interaction occurs in specialized microdomains where ER and plasma membranes are in close apposition
PMID: 26215475
4
STIM1 activates both ORAI and TRPC channels; TRPC channels can function independently of STIM1
PMID: 24961979
5
STIM1 dysregulation contributes to stroke pathogenesis through altered calcium homeostasis
PMID: 34757454
6
STIM1 promotes tumorigenesis and metastasis through invadopodia formation, angiogenesis, and inflammatory responses
PMID: 37194587
7
STIM1 protein stability is regulated by TRIM32-mediated ubiquitination, relevant to cancer metastasis
PMID: 37542345
Disease Associationsβ“˜23
myopathy, tubular aggregate, 1Open Targets
0.78Strong
combined immunodeficiency due to STIM1 deficiencyOpen Targets
0.78Strong
Stormorken syndromeOpen Targets
0.76Strong
tubular aggregate myopathyOpen Targets
0.72Strong
Stormorken-Sjaastad-Langslet syndromeOpen Targets
0.63Moderate
combined immunodeficiencyOpen Targets
0.46Moderate
atrial fibrillationOpen Targets
0.46Moderate
T-B- severe combined immunodeficiencyOpen Targets
0.46Moderate
T-B+ severe combined immunodeficiencyOpen Targets
0.46Moderate
T+ B+ severe combined immunodeficiencyOpen Targets
0.46Moderate
inherited hemoglobinopathyOpen Targets
0.40Weak
familial hemolytic anemiaOpen Targets
0.39Weak
atrial flutterOpen Targets
0.34Weak
sickle cell disease and related diseasesOpen Targets
0.29Weak
mental or behavioural disorderOpen Targets
0.29Weak
hemolytic anemiaOpen Targets
0.28Weak
attention deficit hyperactivity disorderOpen Targets
0.28Weak
myopathy, autophagic vacuolar, infantile-onsetOpen Targets
0.27Weak
neurodegenerative diseaseOpen Targets
0.27Weak
urolithiasisOpen Targets
0.26Weak
Immunodeficiency 10UniProt
Myopathy, tubular aggregate, 1UniProt
Stormorken syndromeUniProt
Pathogenic Variants37
NM_001382567.1(STIM1):c.148C>T (p.Arg50Ter)Pathogenic
Combined immunodeficiency due to STIM1 deficiency|Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates
β˜…β˜…β˜†β˜†2025β†’ Residue 50
NM_001382567.1(STIM1):c.326A>G (p.His109Arg)Pathogenic
Myopathy, tubular aggregate, 1|Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 109
NM_001382567.1(STIM1):c.163_164del (p.Leu55fs)Pathogenic
Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 55
NM_001382567.1(STIM1):c.262A>G (p.Ser88Gly)Pathogenic
Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates;Stormorken syndrome|Stormorken syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 88
NM_001382567.1(STIM1):c.910C>T (p.Arg304Trp)Pathogenic
Stormorken syndrome|Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency|Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 304
NM_001382567.1(STIM1):c.343A>T (p.Ile115Phe)Pathogenic
not provided|Myopathy, tubular aggregate, 1|Stormorken syndrome|Combined immunodeficiency due to STIM1 deficiency;Stormorken syndrome;Myopathy with tubular aggregates
β˜…β˜†β˜†β˜†2025β†’ Residue 115
NM_001382567.1(STIM1):c.1568-1G>TLikely pathogenic
Stormorken syndrome;Myopathy with tubular aggregates;Combined immunodeficiency due to STIM1 deficiency
β˜…β˜†β˜†β˜†2025
NM_001382567.1(STIM1):c.270+1G>CLikely pathogenic
Combined immunodeficiency due to STIM1 deficiency;Stormorken syndrome;Myopathy with tubular aggregates
β˜…β˜†β˜†β˜†2025
NM_001382567.1(STIM1):c.757C>T (p.Arg253Ter)Pathogenic
Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates
β˜…β˜†β˜†β˜†2025β†’ Residue 253
NM_001382567.1(STIM1):c.386-1G>ALikely pathogenic
Stormorken syndrome;Myopathy with tubular aggregates;Combined immunodeficiency due to STIM1 deficiency
β˜…β˜†β˜†β˜†2024
NM_001382567.1(STIM1):c.270+1_270+2insCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGAAAGTGATGAGGLikely pathogenic
Combined immunodeficiency due to STIM1 deficiency;Stormorken syndrome;Myopathy with tubular aggregates
β˜…β˜†β˜†β˜†2024
NM_001382567.1(STIM1):c.1437_1444dup (p.Glu482fs)Pathogenic
Myopathy with tubular aggregates;Combined immunodeficiency due to STIM1 deficiency;Stormorken syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 482
NM_001382567.1(STIM1):c.252T>A (p.Asp84Glu)Likely pathogenic
Myopathy, tubular aggregate, 1
β˜…β˜†β˜†β˜†2024β†’ Residue 84
NM_001382567.1(STIM1):c.869_887del (p.Ile290fs)Pathogenic
Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates;Stormorken syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 290
NM_001382567.1(STIM1):c.1285C>T (p.Arg429Cys)Pathogenic
Combined immunodeficiency due to STIM1 deficiency|Stormorken syndrome;Myopathy with tubular aggregates;Combined immunodeficiency due to STIM1 deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 429
NM_001382567.1(STIM1):c.30G>A (p.Trp10Ter)Pathogenic
Stormorken syndrome;Myopathy with tubular aggregates;Combined immunodeficiency due to STIM1 deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 10
NM_001382567.1(STIM1):c.325C>T (p.His109Tyr)Pathogenic
Myopathy with tubular aggregates;Combined immunodeficiency due to STIM1 deficiency;Stormorken syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 109
NM_001382567.1(STIM1):c.1452del (p.Ile484fs)Pathogenic
Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates;Stormorken syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 484
NM_001382567.1(STIM1):c.216C>A (p.His72Gln)Likely pathogenic
Myopathy, autophagic vacuolar, infantile-onset
β˜…β˜†β˜†β˜†2024β†’ Residue 72
NM_001382567.1(STIM1):c.251A>G (p.Asp84Gly)Pathogenic
Myopathy, tubular aggregate, 1|Myopathy with tubular aggregates
β˜…β˜†β˜†β˜†2024β†’ Residue 84
View on ClinVar β†—
Related Genes
TRPC4Protein interaction100%MAPRE1Protein interaction99%TRPC5Protein interaction97%TRPC3Protein interaction96%HOMER1Protein interaction95%CACNA1CProtein interaction95%
Tissue Expression6 tissues
Ovary
100%
Liver
88%
Lung
85%
Bone Marrow
79%
Brain
54%
Heart
42%
Gene Interaction Network
Click a node to explore
STIM1TRPC4MAPRE1TRPC5TRPC3HOMER1CACNA1C
PROTEIN STRUCTURE
Preparing viewer…
PDB3TEQ Β· 1.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.47Moderately Constrained
pLIβ“˜
0.99Intolerant
Observed/Expected LoF0.34 [0.25–0.47]
RankingsWhere STIM1 stands among ~20K protein-coding genes
  • #445of 20,598
    Most Researched552 Β· top 5%
  • #1,606of 5,498
    Most Pathogenic Variants37
  • #2,745of 17,882
    Most Constrained (LOEUF)0.47 Β· top quartile
Genes detectedSTIM1
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
CRAC channelopathies.
PMID: 20111871
Pflugers Arch Β· 2010
1.00
2
TSPAN18 facilitates bone metastasis of prostate cancer by protecting STIM1 from TRIM32-mediated ubiquitination.
PMID: 37542345
J Exp Clin Cancer Res Β· 2023
0.90
3
CD4⁺ and CD8⁺ T cell-dependent antiviral immunity requires STIM1 and STIM2.
PMID: 25157823
J Clin Invest Β· 2014
0.86
4
Degradation of STIM1 through FAM134B-mediated ER-phagy is potentially involved in cell proliferation.
PMID: 39128711
J Biol Chem Β· 2024
0.84
5
The STIM1-ORAI1 microdomain.
PMID: 26215475
Cell Calcium Β· 2015
0.80