STIM1

stromal interaction molecule 1, the group of MicroRNA protein coding host genes|Sterile alpha motif domain containing

Basic information

Region (hg38): 11:3854527-4093210

Links

ENSG00000167323 ∙ NCBI:6786 ∙ OMIM:605921 ∙ HGNC:11386 ∙ Uniprot:Q13586 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myopathy, tubular aggregate, 1 (Limited), mode of inheritance: AD
• Stormorken syndrome (Supportive), mode of inheritance: AD
• tubular aggregate myopathy (Supportive), mode of inheritance: AD
• combined immunodeficiency due to STIM1 deficiency (Supportive), mode of inheritance: AR
• combined immunodeficiency due to STIM1 deficiency (Strong), mode of inheritance: AR
• myopathy, tubular aggregate, 1 (Strong), mode of inheritance: AD
• combined immunodeficiency due to STIM1 deficiency (Moderate), mode of inheritance: AR
• myopathy, tubular aggregate, 1 (Definitive), mode of inheritance: AD
• tubular aggregate myopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Stormorken syndrome; Immunodeficiency 10	AD/AR	Allergy/Immunology/Infectious; Cardiovascular; Hematologic	In Stormorken syndrome, individuals may demonstrate hematologic anomalies including anemia, thrombocytopenia, and bleeding diathesis, and awareness may allow preventive measures and prompt treatment; Individuals have been described with cardiovascular anomalies (eg, intracranial aneurysms), and awareness may allow surveillance and early management; In Immunodeficiency 10, individuals may suffer early and severe (including fatal) infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals may have hematologic abnormalities, including autoimmune hemolytic anemia and thrombocytopenia, which have been reported as steroid-responsive; HSCT has been reported	Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Dental; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal	19420366; 20876309; 22190180; 23332920; 24570283; 24591628; 24619930; 25577287

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STIM1 gene.

• Myopathy, tubular aggregate, 1 (3 variants)
• Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates;Stormorken syndrome (3 variants)
• Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates (3 variants)
• Combined immunodeficiency due to STIM1 deficiency;Stormorken syndrome;Myopathy with tubular aggregates (3 variants)
• Stormorken syndrome (2 variants)
• not provided (2 variants)
• Combined immunodeficiency due to STIM1 deficiency;Myopathy, tubular aggregate, 1;Stormorken syndrome (1 variants)
• Combined immunodeficiency due to STIM1 deficiency (1 variants)
• Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency (1 variants)
• Stormorken syndrome;Myopathy with tubular aggregates;Combined immunodeficiency due to STIM1 deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STIM1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	154	4	161
missense	4	5	335	7	7	358
nonsense	1		2	1		4
start loss						0
frameshift	6	1				7
inframe indel			10			10
splice donor/acceptor (+/-2bp)		4		1		5
splice region			15	22		37
non coding			8	73	35	116
Total	11	10	358	236	46

Variants in STIM1

This is a list of pathogenic ClinVar variants found in the STIM1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-3855605-G-GCC			Benign (Jul 07, 2018)
11-3855608-C-CG			Benign (Jul 07, 2018)
11-3855613-AC-A			Benign (Jun 23, 2018)
11-3855664-A-G			Benign (Jul 02, 2018)
11-3855844-C-T			Benign (Jul 02, 2018)
11-3855883-CTCTCT-C			Benign (Jun 23, 2018)
11-3856264-T-G			Uncertain significance (Feb 20, 2018)
11-3856274-G-A		Stormorken syndrome;Myopathy with tubular aggregates;Combined immunodeficiency due to STIM1 deficiency	Uncertain significance (Nov 22, 2022)
11-3856277-G-A		not specified • Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates	Uncertain significance (Apr 01, 2024)
11-3856279-A-G		Myopathy with tubular aggregates;Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency	Likely benign (Dec 02, 2022)
11-3856283-G-A		Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates	Uncertain significance (May 09, 2022)
11-3856285-C-T		Myopathy with tubular aggregates;Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency	Likely benign (Jun 25, 2022)
11-3856290-T-C		Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates;Stormorken syndrome	Uncertain significance (Aug 31, 2022)
11-3856292-G-A		Combined immunodeficiency due to STIM1 deficiency;Stormorken syndrome;Myopathy with tubular aggregates • Immunodeficiency, common variable, 10	Uncertain significance (Aug 16, 2022)
11-3856299-G-T		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
11-3856312-ACTC-A		Combined immunodeficiency due to STIM1 deficiency;Stormorken syndrome;Myopathy with tubular aggregates	Uncertain significance (Nov 21, 2023)
11-3856316-C-T		Combined immunodeficiency due to STIM1 deficiency;Stormorken syndrome;Myopathy with tubular aggregates	Uncertain significance (Dec 31, 2022)
11-3856320-T-G		Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates	Uncertain significance (May 14, 2021)
11-3856324-C-T		Myopathy with tubular aggregates;Combined immunodeficiency due to STIM1 deficiency;Stormorken syndrome	Likely benign (Mar 23, 2023)
11-3856327-G-C		Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates	Uncertain significance (Oct 16, 2016)
11-3856328-G-A		Combined immunodeficiency due to STIM1 deficiency;Stormorken syndrome;Myopathy with tubular aggregates • not specified	Uncertain significance (Nov 17, 2023)
11-3856332-A-G		Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates;Stormorken syndrome • Inborn genetic diseases	Uncertain significance (Apr 15, 2024)
11-3856334-A-G		Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates	Uncertain significance (Oct 17, 2023)
11-3856337-C-T		Myopathy with tubular aggregates;Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency	Uncertain significance (Dec 01, 2023)
11-3856338-T-A		Stormorken syndrome;Combined immunodeficiency due to STIM1 deficiency;Myopathy with tubular aggregates	Uncertain significance (Feb 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STIM1	protein_coding	protein_coding	ENST00000300737	12	238683

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.775	0.225	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.12	279	398	0.701	0.0000235	4532
Missense in Polyphen		69	119.06	0.57954		1386
Synonymous	-0.363	158	152	1.04	0.00000831	1319
Loss of Function	4.19	6	31.3	0.192	0.00000173	351

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000355	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000689	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores (PubMed:15866891, PubMed:16005298, PubMed:16208375, PubMed:16537481, PubMed:16733527, PubMed:16766533, PubMed:16807233, PubMed:18854159, PubMed:19249086, PubMed:22464749, PubMed:24069340, PubMed:24351972, PubMed:24591628, PubMed:26322679, PubMed:25326555, PubMed:28219928). Acts as Ca(2+) sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca(2+) release-activated Ca(2+) (CRAC) channel subunit ORAI1 (PubMed:16208375, PubMed:16537481). Involved in enamel formation (PubMed:24621671). Activated following interaction with STIMATE, leading to promote STIM1 conformational switch (PubMed:26322679). {ECO:0000269|PubMed:15866891, ECO:0000269|PubMed:16005298, ECO:0000269|PubMed:16208375, ECO:0000269|PubMed:16537481, ECO:0000269|PubMed:16733527, ECO:0000269|PubMed:16766533, ECO:0000269|PubMed:16807233, ECO:0000269|PubMed:18854159, ECO:0000269|PubMed:19249086, ECO:0000269|PubMed:22464749, ECO:0000269|PubMed:24069340, ECO:0000269|PubMed:24351972, ECO:0000269|PubMed:24591628, ECO:0000269|PubMed:24621671, ECO:0000269|PubMed:25326555, ECO:0000269|PubMed:26322679, ECO:0000269|PubMed:28219928}.
• Disease: DISEASE: Immunodeficiency 10 (IMD10) [MIM:612783]: An immune disorder characterized by recurrent infections, impaired activation and proliferative response of T-cells, decreased T-cell production of cytokines, lymphadenopathy, and normal lymphocytes counts and serum immunoglobulin levels. Additional features include thrombocytopenia, autoimmune hemolytic anemia, myopathy, partial iris hypoplasia, hepatosplenomegaly and defective enamel dentition. {ECO:0000269|PubMed:19420366, ECO:0000269|PubMed:22190180}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myopathy, tubular aggregate, 1 (TAM1) [MIM:160565]: A rare congenital myopathy characterized by regular arrays of membrane tubules on muscle biopsies without additional histopathological hallmarks. Tubular aggregates in muscle are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. They may occur in a variety of circumstances, including inherited myopathies, alcohol- and drug-induced myopathies, exercise-induced cramps or muscle weakness. {ECO:0000269|PubMed:23332920, ECO:0000269|PubMed:24570283, ECO:0000269|PubMed:25326555, ECO:0000269|PubMed:25953320}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Stormorken syndrome (STRMK) [MIM:185070]: A rare autosomal dominant disease characterized by mild bleeding tendency, thrombocytopathy, thrombocytopenia, mild anemia, asplenia, tubular aggregate myopathy, miosis, headache, and ichthyosis. {ECO:0000269|PubMed:24591628, ECO:0000269|PubMed:24619930, ECO:0000269|PubMed:25577287}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Platelet activation - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Signaling by the B Cell Receptor (BCR);Immune System;Adaptive Immune System;Ion homeostasis;Cardiac conduction;Muscle contraction;Hemostasis;Elevation of cytosolic Ca2+ levels;Platelet calcium homeostasis;Platelet homeostasis;TCR signaling in naïve CD8+ T cells;TCR signaling in naïve CD4+ T cells (Consensus)

Recessive Scores

• pRec: 0.167

Intolerance Scores

• loftool: 0.269
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.54

Haploinsufficiency Scores

• pHI: 0.245
• hipred: Y
• hipred_score: 0.662
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.810

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Stim1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; respiratory system phenotype

Gene ontology

• Biological process: store-operated calcium entry;detection of calcium ion;cellular calcium ion homeostasis;activation of store-operated calcium channel activity;positive regulation of adenylate cyclase activity;positive regulation of angiogenesis;regulation of calcium ion transport;enamel mineralization;regulation of cardiac conduction;regulation of store-operated calcium entry
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;microtubule;plasma membrane;integral component of plasma membrane;integral component of endoplasmic reticulum membrane;cortical endoplasmic reticulum;sarcoplasmic reticulum membrane;plasma membrane raft
• Molecular function: protease binding;calcium channel regulator activity;calcium ion binding;protein binding;identical protein binding;microtubule plus-end binding