STIMATE

Summary

STIMATE (STIM activating enhancer, HGNC:30526) is a protein-coding gene on chromosome 3p21.1, encoding Store-operated calcium entry regulator STIMATE (Q86TL2). Acts as a regulator of store-operated Ca(2+) entry (SOCE) at junctional sites that connect the endoplasmic reticulum (ER) and plasma membrane (PM), called ER-plasma membrane (ER-PM) junction or cortical ER.

Enables calcium channel regulator activity. Involved in activation of store-operated calcium channel activity and store-operated calcium entry. Located in cortical endoplasmic reticulum; endoplasmic reticulum membrane; and endoplasmic reticulum-plasma membrane contact site.

Source: NCBI Gene 375346 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_198563

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30526
Approved symbol	STIMATE
Name	STIM activating enhancer
Location	3p21.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC52022
Ensembl gene	ENSG00000213533
Ensembl biotype	protein_coding
OMIM	617189
Entrez	375346

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000355083, ENST00000464769, ENST00000467979, ENST00000477591, ENST00000482155, ENST00000485356, ENST00000902083, ENST00000924009, ENST00000963054

RefSeq mRNA: 1 — MANE Select: NM_198563 NM_198563

CCDS: CCDS2866

Canonical transcript exons

ENST00000355083 — 8 exons

Exon	Start	End
ENSE00001498283	52897291	52897548
ENSE00001879972	52836733	52840610
ENSE00003496987	52849792	52849913
ENSE00003524455	52843721	52843798
ENSE00003572442	52855396	52855444
ENSE00003587573	52852603	52852698
ENSE00003617039	52842811	52842960
ENSE00003620815	52844829	52844941

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 92.23.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9484 / max 28.5508, expressed in 431 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42489	14.1058	1796
42488	0.8959	401
42486	0.0292	16
42485	0.0232	7

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	92.23	gold quality
liver	UBERON:0002107	90.39	gold quality
skeletal muscle tissue	UBERON:0001134	89.37	gold quality
right uterine tube	UBERON:0001302	88.98	gold quality
popliteal artery	UBERON:0002250	88.55	gold quality
tibial artery	UBERON:0007610	88.54	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.80	gold quality
muscle tissue	UBERON:0002385	87.51	gold quality
right coronary artery	UBERON:0001625	87.33	gold quality
thoracic aorta	UBERON:0001515	87.07	gold quality
fallopian tube	UBERON:0003889	87.07	gold quality
ascending aorta	UBERON:0001496	87.04	gold quality
bone marrow	UBERON:0002371	86.81	gold quality
bone marrow cell	CL:0002092	86.72	gold quality
descending thoracic aorta	UBERON:0002345	86.64	gold quality
left coronary artery	UBERON:0001626	86.57	gold quality
blood	UBERON:0000178	86.22	gold quality
muscle of leg	UBERON:0001383	85.63	gold quality
stromal cell of endometrium	CL:0002255	85.35	gold quality
monocyte	CL:0000576	85.11	gold quality
leukocyte	CL:0000738	84.95	gold quality
mucosa of stomach	UBERON:0001199	84.91	gold quality
sural nerve	UBERON:0015488	84.61	gold quality
gastrocnemius	UBERON:0001388	84.48	gold quality
urinary bladder	UBERON:0001255	84.39	gold quality
granulocyte	CL:0000094	84.10	gold quality
tonsil	UBERON:0002372	83.50	gold quality
body of pancreas	UBERON:0001150	83.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.74	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	2258.68
E-ANND-3	no	1.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

134 targeting STIMATE, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 2)

• Data show that transmembrane protein 110 STIMATE is an endoplasmic reticulum (ER)-resident protein that co-localizes with membrane protein STIM1. (PMID:26322679)
• Research on calcium signaling has centered on STIM1, ORAI1, and proteins that modulate their function. TMEM110 regulates the maintenance of ER-plasma membrane junctions and the short-term remodeling of junctions during store-dependent calcium signaling. (PMID:26644574)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	stimate	ENSDARG00000013694
mus_musculus	Stimate	ENSMUSG00000006526
rattus_norvegicus	Stimate	ENSRNOG00000017051

Paralogs (1): MUSTN1 (ENSG00000272573)

Protein

Protein identifiers

Store-operated calcium entry regulator STIMATE — Q86TL2 (reviewed: Q86TL2)

Alternative names: STIM-activating enhancer encoded by TMEM110, Transmembrane protein 110

All UniProt accessions (4): F8WDI5, H7C503, H7C551, Q86TL2

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a regulator of store-operated Ca(2+) entry (SOCE) at junctional sites that connect the endoplasmic reticulum (ER) and plasma membrane (PM), called ER-plasma membrane (ER-PM) junction or cortical ER. SOCE is a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Acts by interacting with STIM1, promoting STIM1 conformational switch. Involved in STIM1 relocalization to ER-PM junctions. Contributes to the maintenance and reorganization of store-dependent ER-PM junctions.

Subunit / interactions. Homooligomer. Interacts with STIM1.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed.

Domain organisation. The GXXXG motif may mediate oligomerization. The C-terminus is necessary for its localization at ER-plasma membrane (ER-PM) junctions as well as for the store-dependent rearrangement of ER-PM junctions.

Similarity. Belongs to the STIMATE family.

RefSeq proteins (1): NP_940965* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022127	STIMATE/YPL162C	Family

Pfam: PF12400

UniProt features (13 total): transmembrane region 5, region of interest 3, topological domain 2, chain 1, short sequence motif 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86TL2-F1	69.62	0.21

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (1):

Position	Phenotype
241–246	induces relocalization to cell membrane.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 146 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_POSITIVE_REGULATION_OF_CATION_CHANNEL_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_POSITIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, AP4_01, GOBP_REGULATION_OF_TRANSMEMBRANE_TRANSPORT

GO Biological Process (2): store-operated calcium entry (GO:0002115), activation of store-operated calcium channel activity (GO:0032237)

GO Molecular Function (2): calcium channel regulator activity (GO:0005246), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), cortical endoplasmic reticulum (GO:0032541), endoplasmic reticulum-plasma membrane contact site (GO:0140268), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
calcium ion transport	1
positive regulation of store-operated calcium channel activity	1
calcium channel activity	1
ion channel regulator activity	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
cell cortex	1
endoplasmic reticulum tubular network	1
organelle membrane contact site	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

924 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STIMATE	SARAF	Q96BY9	781
STIMATE	ORAI1	Q96D31	702
STIMATE	CRACR2A	Q9BSW2	698
STIMATE	STIM1	Q13586	669
STIMATE	ESYT1	Q9BSJ8	594
STIMATE	ESYT3	A0FGR9	581
STIMATE	SLC35G1	Q2M3R5	568
STIMATE	NT5DC2	Q9H857	510
STIMATE	JPH4	Q96JJ6	506
STIMATE	ASPH	Q12797	480
STIMATE	STIM2	Q9P246	464
STIMATE	NAPA	P54920	452
STIMATE	NEK4	P51957	421
STIMATE	MUSTN1	Q8IVN3	420
STIMATE	OSBPL5	Q9H0X9	403

IntAct

4 interactions, top by confidence:

A	B	Type	Score
STIMATE	CCR4	psi-mi:“MI:0915”(physical association)	0.370
CFTR	STIMATE	psi-mi:“MI:0915”(physical association)	0.370
GPR151	TSPAN15	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): TMEM110 (Two-hybrid), TMEM110 (Affinity Capture-RNA), TMEM110 (Affinity Capture-MS), TMEM110 (PCA), TMEM110 (Cross-Linking-MS (XL-MS)), TMEM110 (Proximity Label-MS)

ESM2 similar proteins: A2VDL9, A9UY97, F4JY11, G4YM00, G4Z2L3, O17204, O42579, P15920, P16393, P20715, P30628, P36142, P54960, P70549, P93766, Q09906, Q18071, Q1RMW2, Q29BL9, Q2U0S9, Q3UF25, Q3UFJ6, Q4QQS1, Q54PI4, Q54WM0, Q5BPZ5, Q5FWM8, Q5RBL0, Q5XIT3, Q5Z413, Q61086, Q651J5, Q657S5, Q6P6G5, Q6VVA6, Q6ZMB5, Q7TSW6, Q86TL2, Q8BG09, Q8MRQ4

Diamond homologs: Q3UF25, Q7TSW6, Q86TL2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

4 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1911 predictions. Top by Δscore:

Variant	Effect	Δscore
3:52840520:T:TA	donor_gain	1.0000
3:52840610:TC:T	acceptor_loss	1.0000
3:52840611:C:CA	acceptor_loss	1.0000
3:52840611:C:CC	acceptor_gain	1.0000
3:52842805:CCCTA:C	donor_loss	1.0000
3:52842806:CCTAC:C	donor_loss	1.0000
3:52842807:CTA:C	donor_loss	1.0000
3:52842807:CTACC:C	donor_loss	1.0000
3:52842808:TACCT:T	donor_loss	1.0000
3:52842809:A:T	donor_loss	1.0000
3:52842810:C:A	donor_loss	1.0000
3:52842820:AGACT:A	donor_gain	1.0000
3:52842956:AAAGC:A	acceptor_gain	1.0000
3:52842957:AAGC:A	acceptor_gain	1.0000
3:52842958:AGC:A	acceptor_gain	1.0000
3:52842959:GC:G	acceptor_gain	1.0000
3:52842960:CC:C	acceptor_gain	1.0000
3:52842960:CCTGT:C	acceptor_loss	1.0000
3:52842961:C:A	acceptor_loss	1.0000
3:52842961:C:CC	acceptor_gain	1.0000
3:52842962:T:A	acceptor_loss	1.0000
3:52843715:A:AC	donor_gain	1.0000
3:52843716:C:CC	donor_gain	1.0000
3:52843719:A:AC	donor_gain	1.0000
3:52843720:C:CC	donor_gain	1.0000
3:52843720:CG:C	donor_gain	1.0000
3:52843796:CACCT:C	acceptor_loss	1.0000
3:52843797:ACCT:A	acceptor_loss	1.0000
3:52843798:CCTGT:C	acceptor_loss	1.0000
3:52843799:C:CA	acceptor_loss	1.0000

AlphaMissense

1926 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:52842938:T:A	D214V	1.000
3:52842938:T:G	D214A	1.000
3:52843734:G:T	P202H	1.000
3:52852680:T:A	K76N	1.000
3:52852680:T:G	K76N	1.000
3:52855440:T:A	K55N	1.000
3:52855440:T:G	K55N	1.000
3:52842937:G:C	D214E	0.999
3:52842937:G:T	D214E	0.999
3:52842938:T:C	D214G	0.999
3:52842939:C:A	D214Y	0.999
3:52842939:C:G	D214H	0.999
3:52842948:A:G	W211R	0.999
3:52842948:A:T	W211R	0.999
3:52843721:G:C	N206K	0.999
3:52843721:G:T	N206K	0.999
3:52843734:G:C	P202R	0.999
3:52843735:G:A	P202S	0.999
3:52843735:G:T	P202T	0.999
3:52843737:A:T	V201D	0.999
3:52843743:A:G	L199P	0.999
3:52844918:A:G	W151R	0.999
3:52844918:A:T	W151R	0.999
3:52849795:A:G	Y142H	0.999
3:52849800:C:A	G140V	0.999
3:52849800:C:T	G140D	0.999
3:52849878:C:T	G114D	0.999
3:52849879:C:G	G114R	0.999
3:52849890:T:A	D110V	0.999
3:52849890:T:G	D110A	0.999

dbSNP variants (sampled 300 via entrez): RS1000004747 (3:52842960 C>A,G), RS1000017797 (3:52851605 C>A), RS1000030087 (3:52840397 G>A), RS1000117991 (3:52846084 C>T), RS1000142464 (3:52891788 T>A,C), RS1000146688 (3:52881875 G>A), RS1000185018 (3:52875971 T>A,C,G), RS1000219037 (3:52880739 C>T), RS1000252568 (3:52846315 G>A), RS1000257897 (3:52885768 T>C,G), RS1000268134 (3:52897720 T>C,G), RS1000291132 (3:52846700 A>G), RS1000351332 (3:52873442 C>G), RS1000363530 (3:52891472 A>T), RS1000372248 (3:52869780 T>C)

Disease associations

OMIM: gene MIM:617189 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST001241_15	Bipolar disorder	2.000000e-06
GCST001535_11	Immune reponse to smallpox (secreted IL-2)	5.000000e-07
GCST002149_14	Schizophrenia	1.000000e-08
GCST002539_48	Schizophrenia	4.000000e-11
GCST004125_5	Type 2 diabetes (age of onset)	8.000000e-06
GCST004521_123	Autism spectrum disorder or schizophrenia	3.000000e-12
GCST004521_203	Autism spectrum disorder or schizophrenia	4.000000e-08
GCST004521_259	Autism spectrum disorder or schizophrenia	6.000000e-09
GCST006269_1034	General cognitive ability	2.000000e-08
GCST006269_1115	General cognitive ability	4.000000e-10
GCST006803_55	Schizophrenia	1.000000e-11
GCST008103_3	Bipolar disorder	7.000000e-11
GCST008810_57	Smoking initiation (ever regular vs never regular)	8.000000e-11
GCST010169_2	Midgestational total 25-hydroxyvitamin D levels (fetal genetic effect)	2.000000e-06
GCST010988_144	Adult body size	3.000000e-13
GCST011122_44	Walking pace	3.000000e-10
GCST012228_64	Waist-hip index	4.000000e-08
GCST90002391_14	Mean corpuscular hemoglobin concentration	2.000000e-09
GCST90020024_1212	A body shape index	2.000000e-15
GCST90020024_1214	A body shape index	1.000000e-14
GCST90020025_1347	Waist-to-hip ratio adjusted for BMI	1.000000e-13
GCST90020027_145	Waist-hip index	1.000000e-13
GCST90020029_1201	Waist circumference adjusted for body mass index	5.000000e-15

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004337	intelligence
EFO:0005670	smoking initiation
EFO:0007959	fetal genotype effect measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
Aflatoxin B1	increases methylation	2
bisphenol A	decreases methylation	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	increases expression	1
Fulvestrant	increases methylation	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Carbamazepine	affects expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Niclosamide	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	increases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0Q9	Ubigene HeLa STIMATE KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.