STOML2

Summary

STOML2 (stomatin like 2, HGNC:14559) is a protein-coding gene on chromosome 9p13.3, encoding Stomatin-like protein 2, mitochondrial (Q9UJZ1). Mitochondrial protein that probably regulates the biogenesis and the activity of mitochondria.

Enables GTPase binding activity; T cell receptor binding activity; and cardiolipin binding activity. Involved in intracellular calcium ion homeostasis; mitochondrion organization; and protein complex oligomerization. Acts upstream of or within T cell receptor signaling pathway. Located in several cellular components, including immunological synapse; membrane raft; and mitochondrial envelope.

Source: NCBI Gene 30968 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• Druggable target: yes
• MANE Select transcript: NM_013442

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14559
Approved symbol	STOML2
Name	stomatin like 2
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	SLP-2, HSPC108
Ensembl gene	ENSG00000165283
Ensembl biotype	protein_coding
OMIM	608292
Entrez	30968

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000356493, ENST00000452248, ENST00000487490, ENST00000488050, ENST00000619795, ENST00000873208, ENST00000873209, ENST00000940080, ENST00000940081, ENST00000940082, ENST00000940083, ENST00000940084, ENST00000940085, ENST00000940086, ENST00000940087, ENST00000940088, ENST00000940089

RefSeq mRNA: 4 — MANE Select: NM_013442 NM_001287031, NM_001287032, NM_001287033, NM_013442

CCDS: CCDS6577, CCDS69588, CCDS75830

Canonical transcript exons

ENST00000356493 — 10 exons

Exon	Start	End
ENSE00001091877	35101135	35101279
ENSE00001091879	35100932	35101011
ENSE00001091881	35102686	35102823
ENSE00001091885	35100598	35100726
ENSE00001150810	35101426	35101560
ENSE00001411425	35103050	35103131
ENSE00003239244	35099778	35100172
ENSE00003288725	35102095	35102194
ENSE00003371234	35101710	35101811
ENSE00003628309	35101904	35101962

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 84.6674 / max 332.9206, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100566	79.3470	1823
100567	3.6749	1594
100568	1.6455	1184

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.01	gold quality
mucosa of transverse colon	UBERON:0004991	97.61	gold quality
right adrenal gland	UBERON:0001233	97.57	gold quality
right adrenal gland cortex	UBERON:0035827	97.48	gold quality
gastrocnemius	UBERON:0001388	97.39	gold quality
left adrenal gland	UBERON:0001234	97.29	gold quality
left adrenal gland cortex	UBERON:0035825	97.18	gold quality
muscle of leg	UBERON:0001383	96.92	gold quality
heart left ventricle	UBERON:0002084	96.91	gold quality
body of stomach	UBERON:0001161	96.84	gold quality
transverse colon	UBERON:0001157	96.82	gold quality
rectum	UBERON:0001052	96.78	gold quality
cardiac ventricle	UBERON:0002082	96.69	gold quality
right atrium auricular region	UBERON:0006631	96.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.60	gold quality
lower esophagus	UBERON:0013473	96.57	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.57	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.46	gold quality
metanephros cortex	UBERON:0010533	96.43	gold quality
right ovary	UBERON:0002118	96.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.41	gold quality
adrenal cortex	UBERON:0001235	96.37	gold quality
right uterine tube	UBERON:0001302	96.35	gold quality
esophagus	UBERON:0001043	96.32	gold quality
esophagus mucosa	UBERON:0002469	96.31	gold quality
body of pancreas	UBERON:0001150	96.26	gold quality
left uterine tube	UBERON:0001303	96.25	gold quality
skin of leg	UBERON:0001511	96.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.25	gold quality
adrenal gland	UBERON:0002369	96.19	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	24.70
E-MTAB-9067	yes	21.57
E-MTAB-9801	yes	6.00
E-MTAB-10042	yes	5.55
E-CURD-11	no	337.36
E-MTAB-7037	no	259.80
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
MFN2	Activation
OPA1	Activation
PPARGC1A	Activation

miRNA regulators (miRDB)

23 targeting STOML2, 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-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-4515	95.70	65.73	716

Literature-anchored findings (GeneRIF, showing 40)

• overexpression of stomatin-like protein 2 is associated with neoplasms (PMID:16533792)
• SLP-2 is a high abundance protein in several tissues and cells and may play an important biological role; this study uses mass spectrometry to analyze its primary structure (PMID:16671055)
• SLP-2 was overexpressed in endometrial adenocarcinoma compared with their normal counterparts. (PMID:17342323)
• High-level SLP-2 expression was associated with decreased overall survival (P = .011) and was more often found in patients with tumors larger than 20 mm, lymph node metastasis, advanced clinical stage, distant metastasis (PMID:17709317)
• Endosymbiotic origin of paraslipin from an alphaprotoebacterial ancestor (SLP-2) (PMID:18267007)
• SLP-2 is an important player in T cell activation by ensuring sustained TCR signaling (PMID:18641330)
• Familial MGUS and multiple myeloma were associated with a dominant inheritance of hyperphosphorylated paratarg-7 (PMID:19767238)
• SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in pulmonary squamous cell carcinoma. (PMID:19839737)
• negatively modulates mitochondrial sodium-calcium exchange (PMID:19944461)
• plasma concentrations of stomatin (EPB72)-like 2 in early-stage colorectal cancer patients were elevated as compared with those of healthy individuals (PMID:21209152)
• The dominant inheritance of hyperphosphorylated paratarg-7 explains cases of familial IgM monoclonal gammopathy of undetermined significance and Waldenstrom macroglobulinemia (PMID:21220746)
• [review] Stomatin family member STOML2 is oligomeric; it localizes mostly to membrane domains and has been shown to modulate ion channel activity. (PMID:21501885)
• We propose that the function of SLP-2 is to recruit prohibitins to cardiolipin to form cardiolipin-enriched microdomains in which electron transport complexes are optimally assembled. (PMID:21746876)
• SLP-2 and HER2/neu can play a role in lymph node/distant metastases of breast cancers (PMID:22081131)
• investigation of biomarkers for early diagnosis of endometriosis: Data suggest that SLP2, tropomyosin 3, and tropomodulin 3 are autoantigens present in blood of women with endometriosis; immunodominant epitopes were identified. (PMID:22158085)
• SLP-2 facilitates the compartmentalization not only of mitochondrial membranes but also of the plasma membrane into functional microdomains. (PMID:22623988)
• SLP-2 deficiency in T-lymphocytes is associated with abnormal cardiolipin compartmentalization in mitochondrial membranes, defects associated with altered mitochondrial respiration that is increasingly uncoupled from ATP production. (PMID:23028053)
• Increased levels of SLP-2 correlate with lymph node metastasis in gastric cancer. (PMID:23371255)
• Expression of SLP-2 is associated with invasion of esophageal squamous cell carcinoma. (PMID:23667687)
• SLP-2 may play an important role in human GBC tumorigenesis, and SLP-2 might serve as a novel prognostic marker in human GBC. (PMID:23918306)
• SLP-2 was upregulated by TGF-beta1, indicating a possible role of SLP-2 in Papillary thyroid cancer tumorigenesis. (PMID:24190591)
• STOML2 may have a role in progression of gastric adenocarcinoma (PMID:24258357)
• STOML2 was correlated to progression in cervical cancer, and implicated it as a potential predictive factor for the prognosis of cervical cancer. (PMID:25973071)
• Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival (PMID:26487491)
• The significant association of SLP-2 overexpression with unfavorable clinicopathological characteristics and BRAFV600E mutation indicates that SLP-2 may have a role in aggressiveness of BRAF-mutated papillary thyroid carcinoma. (PMID:26750533)
• The expression of STOML2, a gene that plays a key role in mitochondrial function and T-cell activation, is associated with both IL-6 signaling and asthma risk. (PMID:26932604)
• results reveal an important role of SLP2 membrane scaffolds for the spatial organization of inner membrane proteases regulating mitochondrial dynamics, quality control, and cell survival. (PMID:27737933)
• Slp2 is involved in endometrial stromal cell proliferation and differentiation during decidualization in mice and humans (PMID:27986413)
• The downregulation of SLP-2 by siRNA inhibited cell proliferation, elevated caspase3 activity, and decreased CCBE1 expression (PMID:29364474)
• Data show that SLP-2 is upregulated by high cisplatin concentrations, leading to increased protein turnover. Overexpression of SLP-2 activates the MEK/ERK signaling pathway, and suppresses the mitochondrial apoptosis pathway, indicating that SLP-2 inhibits apoptosis by activating the MEK/ERK pathway and inhibiting the mitochondrial apoptosis pathway in cervical cancer cells. (PMID:29516570)
• SLP-2 promotes non-small cell lung cancer cell proliferation by enhancing survivin expression mediated through the TCF4/beta-catenin pathway. (PMID:29556045)
• TROP-2, SLP-2 and CD56 were effective diagnostic markers for PTC, especially when they were combined to use. (PMID:29951933)
• The knockdown of STOML2 significantly repressed the viability, migration, and invasion of LM3 cells. Authors observed that silencing STOML2 markedly downregulated the expression levels of MMP-2, MMP-9,MTA1, and nuclear factor kappa B (NF-kappaB), and upregulated levels of E-cadherin, tissue inhibitor of metalloproteinases 2 (TIMP2), and the inhibitor of kappa B (IkappaB). (PMID:30359340)
• that SLP-2 may predict a poor prognosis in colorectal cancer patients as a novel marker (PMID:30389319)
• These findings demonstrated a positive feedback loop of SLP2 which leads to acceleration of tumor progression and poor survival of gastric cancer patients. This finding also provided evidence for the reason of SLP2 elevation. (PMID:30555578)
• Hyperphosphorylated paratarg-7 carrier state is a strong molecularly defined risk factor for the development of Waldenstrom’s macroglobulinaemia. (PMID:30888245)
• Clinical significance of SLP-2 in epithelial ovarian cancer and its regulatory effect on the Notch signaling pathway. (PMID:32141532)
• Stomatin-like protein 2 (SLP2) regulates the proliferation and invasion of trophoblast cells by modulating mitochondrial functions. (PMID:32814233)
• Characterization of the interactome of c-Src within the mitochondrial matrix by proximity-dependent biotin identification. (PMID:33412331)
• STOML2 potentiates metastasis of hepatocellular carcinoma by promoting PINK1-mediated mitophagy and regulates sensitivity to lenvatinib. (PMID:33446239)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stoml2	ENSDARG00000103135
mus_musculus	Stoml2	ENSMUSG00000028455
rattus_norvegicus	Stoml2	ENSRNOG00000009535
drosophila_melanogaster	Stoml2	FBGN0034936
caenorhabditis_elegans	stl-1	WBGENE00006061

Paralogs (4): STOML1 (ENSG00000067221), NPHS2 (ENSG00000116218), STOML3 (ENSG00000133115), STOM (ENSG00000148175)

Protein

Protein identifiers

Stomatin-like protein 2, mitochondrial — Q9UJZ1 (reviewed: Q9UJZ1)

Alternative names: EPB72-like protein 2, Paraprotein target 7

All UniProt accessions (3): A0A087WYB4, Q9UJZ1, F2Z2I8

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial protein that probably regulates the biogenesis and the activity of mitochondria. Stimulates cardiolipin biosynthesis, binds cardiolipin-enriched membranes where it recruits and stabilizes some proteins including prohibitin and may therefore act in the organization of functional microdomains in mitochondrial membranes. Through regulation of the mitochondrial function may play a role into several biological processes including cell migration, cell proliferation, T-cell activation, calcium homeostasis and cellular response to stress. May play a role in calcium homeostasis through negative regulation of calcium efflux from mitochondria. Required for mitochondrial hyperfusion a pro-survival cellular response to stress which results in increased ATP production by mitochondria. May also regulate the organization of functional domains at the plasma membrane and play a role in T-cell activation through association with the T-cell receptor signaling complex and its regulation.

Subunit / interactions. Forms homooligomers. Interacts with MFN2; may form heterooligomers. Interacts with CACNA2D2. Interacts with PHB1 and PHB2; recruits them to cardiolipin-enriched mitochondrial membranes and stabilizes them.

Subcellular location. Cell membrane. Mitochondrion. Mitochondrion inner membrane. Mitochondrion intermembrane space. Membrane raft. Cytoplasm. Cytoskeleton.

Tissue specificity. Ubiquitously expressed at low levels. Expressed in lymphoid tissues (at protein level).

Post-translational modifications. Hyperphosphorylated at Ser-17 in some patients with monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and Waldenstrom macroglobulinemia due to impaired dephosphorylation by PP2A.

Induction. Up-regulated in activated B- and T-cells and upon mitochondrial stress by chloramphenicol.

Miscellaneous. Paratarg-7/STOML2 is a frequent autoantigenic target in monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and Waldenstrom macroglobulinemia, 3 B-cell neoplasms associated with excessive secretion of a single monoclonal gammaglobulin (also named paraprotein) in the blood.

Similarity. Belongs to the band 7/mec-2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UJZ1-1	1	yes
Q9UJZ1-2	2

RefSeq proteins (4): NP_001273960, NP_001273961, NP_001273962, NP_038470* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001107	Band_7	Domain
IPR001972	Stomatin_HflK_fam	Family
IPR032435	STML2-like_C	Domain
IPR036013	Band_7/SPFH_dom_sf	Homologous_superfamily
IPR050710	Band7/mec-2_domain	Family

Pfam: PF01145, PF16200

UniProt features (17 total): modified residue 7, sequence conflict 3, transit peptide 1, chain 1, splice variant 1, sequence variant 1, region of interest 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJZ1-F1	81.00	0.61

Functional residue map

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

Post-translational modifications (7): 327, 330, 17, 124, 145, 145, 233

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-8949664	Processing of SMDT1
R-HSA-9840373	Cellular response to mitochondrial stress
R-HSA-2262752	Cellular responses to stress
R-HSA-382551	Transport of small molecules
R-HSA-8949215	Mitochondrial calcium ion transport
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 296 (showing top): FREAC2_01, HNF3ALPHA_Q6, LFA1_Q6, ENK_UV_RESPONSE_KERATINOCYTE_UP, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MORF_RAD21, AP4_Q6, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOMF_GTPASE_BINDING, CAGCTG_AP4_Q5

GO Biological Process (10): intracellular calcium ion homeostasis (GO:0006874), mitochondrion organization (GO:0007005), lipid localization (GO:0010876), positive regulation of interleukin-2 production (GO:0032743), mitochondrial protein processing (GO:0034982), CD4-positive, alpha-beta T cell activation (GO:0035710), proton motive force-driven mitochondrial ATP synthesis (GO:0042776), T cell receptor signaling pathway (GO:0050852), protein complex oligomerization (GO:0051259), stress-induced mitochondrial fusion (GO:1990046)

GO Molecular Function (5): T cell receptor binding (GO:0042608), GTPase binding (GO:0051020), cardiolipin binding (GO:1901612), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (10): immunological synapse (GO:0001772), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), membrane raft (GO:0045121), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Mitochondrial calcium ion transport	1
Cellular responses to stress	1
Cellular responses to stimuli	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
mitochondrion	2
binding	2
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
organelle organization	1
macromolecule localization	1
positive regulation of cytokine production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
protein processing	1
alpha-beta T cell activation	1
oxidative phosphorylation	1
proton motive force-driven ATP synthesis	1
antigen receptor-mediated signaling pathway	1
protein-containing complex assembly	1
mitochondrial fusion	1
cellular response to stress	1
signaling receptor binding	1
protein-containing complex binding	1
enzyme binding	1
phosphatidylglycerol binding	1
plasma membrane	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
membrane	1
cell periphery	1
cytoskeleton	1
membrane microdomain	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2858 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STOML2	PHB1	P35232	750
STOML2	PHB2	Q99623	628
STOML2	YME1L1	Q96TA2	536
STOML2	VDAC2	P45880	528
STOML2	PPEF1	O14829	527
STOML2	GDI2	P50395	515
STOML2	CLCC1	Q96S66	482
STOML2	RILP	Q96NA2	464
STOML2	VPS39	Q96JC1	451
STOML2	HSBP1L1	C9JCN9	449
STOML2	HSBP1	O75506	447
STOML2	ERC1	Q8IUD2	438
STOML2	YIPF6	Q96EC8	436
STOML2	PYM1	Q9BRP8	419
STOML2	FAM228B	P0C875	409

IntAct

194 interactions, top by confidence:

A	B	Type	Score
STK4	RASSF2	psi-mi:“MI:0914”(association)	0.930
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
rep	PHB1	psi-mi:“MI:0914”(association)	0.640
rep	EIF4E2	psi-mi:“MI:0914”(association)	0.640
	STOML2	psi-mi:“MI:0915”(physical association)	0.590
STOML2		psi-mi:“MI:0915”(physical association)	0.590
RABAC1	STOML2	psi-mi:“MI:0915”(physical association)	0.560
STOML2	PEX1	psi-mi:“MI:0915”(physical association)	0.560
STOML2	ATXN2	psi-mi:“MI:0915”(physical association)	0.560
STOML2	WFS1	psi-mi:“MI:0915”(physical association)	0.560
DLD	PDHB	psi-mi:“MI:0914”(association)	0.530
PRKAR1A	AKAP3	psi-mi:“MI:0914”(association)	0.530
APOOL	MTX2	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
GLP1R	STOML2	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (371): STOML2 (Affinity Capture-MS), STOML2 (Affinity Capture-MS), STOML2 (Affinity Capture-MS), STOML2 (Affinity Capture-MS), STOML2 (Affinity Capture-MS), MRPL40 (Co-fractionation), PHB (Co-fractionation), PHB2 (Co-fractionation), STOML2 (Co-fractionation), STOML2 (Co-fractionation), STOML2 (Co-fractionation), STOML2 (Co-fractionation), STOML2 (Co-fractionation), STOML2 (Co-fractionation), STOML2 (Co-fractionation)

ESM2 similar proteins: A3QMC6, A9UMS3, H1VAN0, H1VPS8, H2FLJ1, O04331, O08917, O13127, O35129, O49460, O60121, O61491, O75477, O75955, O94550, P16148, P24156, P26659, P27105, P40961, P50085, P50093, P54116, P72655, P77306, Q28DX1, Q2HJ97, Q32LL2, Q4FZT0, Q54GI9, Q54Q31, Q5RB19, Q5RBL4, Q5RCJ9, Q5XIH7, Q5ZMN3, Q7YR41, Q8TAV4, Q91X78, Q99623

Diamond homologs: H2FLJ1, O26788, O28852, O59180, O60121, P0AA53, P0AA54, P0AA55, P0AA56, P0DKS0, P27105, P54116, P63694, P72655, P9WPR8, P9WPR9, Q16TM5, Q19200, Q19958, Q27433, Q32LL2, Q4FZT0, Q58237, Q6PE84, Q7PPU9, Q8TAV4, Q99JB2, Q9UJZ1, Q9V0Y1, Q9VZA4, P0ABC7, P0ABC8, P40605, Q20657, Q21190, Q22165, Q5UP73, Q9KV09, Q9UBI4, Q8CI66

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
STOML2	“up-regulates activity”	CD3E	binding
STOML2	“up-regulates activity”	LCK	binding
STOML2	“up-regulates activity”	ZAP70	binding
STOML2	“up-regulates activity”	PLCG1	binding
STOML2	“up-regulates quantity by expression”	PPARGC1A	“transcriptional regulation”
STOML2	“up-regulates quantity by expression”	MFN2	“transcriptional regulation”
STOML2	“up-regulates quantity by expression”	OPA1	“transcriptional regulation”
STOML2	“up-regulates activity”	NDUFV1
STOML2	“up-regulates activity”	SDHD
STOML2	“up-regulates quantity”	ATP

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 200 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial protein import	7	9.2×	1e-03
RHOQ GTPase cycle	6	8.5×	4e-03
Mitochondrial protein degradation	9	8.0×	4e-04
Mitochondrial biogenesis	6	7.9×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1049 predictions. Top by Δscore:

Variant	Effect	Δscore
9:35100592:TCTAA:T	donor_loss	1.0000
9:35100593:CTAA:C	donor_loss	1.0000
9:35100594:TAA:T	donor_loss	1.0000
9:35100595:AACCT:A	donor_loss	1.0000
9:35100596:A:C	donor_loss	1.0000
9:35100597:CC:C	donor_loss	1.0000
9:35100722:CCATT:C	acceptor_gain	1.0000
9:35100723:CATT:C	acceptor_gain	1.0000
9:35100723:CATTC:C	acceptor_gain	1.0000
9:35100724:ATT:A	acceptor_gain	1.0000
9:35100724:ATTC:A	acceptor_loss	1.0000
9:35100725:TT:T	acceptor_gain	1.0000
9:35100725:TTCTG:T	acceptor_loss	1.0000
9:35100726:TCTG:T	acceptor_loss	1.0000
9:35100727:C:A	acceptor_loss	1.0000
9:35100727:C:CC	acceptor_gain	1.0000
9:35100728:T:G	acceptor_loss	1.0000
9:35100734:C:CT	acceptor_gain	1.0000
9:35100736:C:CT	acceptor_gain	1.0000
9:35100737:A:T	acceptor_gain	1.0000
9:35100928:TCA:T	donor_loss	1.0000
9:35100930:A:AC	donor_gain	1.0000
9:35100930:A:T	donor_loss	1.0000
9:35100931:C:CC	donor_gain	1.0000
9:35100931:CATG:C	donor_gain	1.0000
9:35100931:CATGT:C	donor_gain	1.0000
9:35101007:CTCTC:C	acceptor_gain	1.0000
9:35101009:CTC:C	acceptor_gain	1.0000
9:35101010:TC:T	acceptor_gain	1.0000
9:35101011:CC:C	acceptor_gain	1.0000

AlphaMissense

2274 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:35101255:C:G	A202P	1.000
9:35101273:C:G	A196P	1.000
9:35100678:C:G	A285P	0.999
9:35100695:G:T	A279D	0.999
9:35100985:C:G	A251P	0.999
9:35101006:C:G	A244P	0.999
9:35101141:C:G	A240P	0.999
9:35101168:C:G	A231P	0.999
9:35101189:C:G	A224P	0.999
9:35101207:C:G	A218P	0.999
9:35101227:C:G	R211P	0.999
9:35101240:A:G	S207P	0.999
9:35101266:C:G	R198P	0.999
9:35101500:C:G	G169R	0.999
9:35101765:G:T	A130D	0.999
9:35100662:G:T	A290D	0.998
9:35100683:A:T	V283D	0.998
9:35100696:C:G	A279P	0.998
9:35100704:A:G	L276P	0.998
9:35100973:C:G	A255P	0.998
9:35101000:C:G	A246P	0.998
9:35101174:A:G	S229P	0.998
9:35101219:C:G	A214P	0.998
9:35101222:A:G	S213P	0.998
9:35101245:A:G	L205P	0.998
9:35101257:C:G	R201P	0.998
9:35101489:G:C	C172W	0.998
9:35101491:A:G	C172R	0.998
9:35101503:A:G	W168R	0.998
9:35101503:A:T	W168R	0.998

dbSNP variants (sampled 300 via entrez): RS1000472513 (9:35101773 G>A,C), RS1000712162 (9:35102070 A>G), RS1001434604 (9:35102982 G>A,C), RS1001445158 (9:35103767 T>C), RS1002036528 (9:35101095 C>A,T), RS1002475225 (9:35104756 T>A), RS1002617889 (9:35104534 G>A,T), RS1003011427 (9:35101046 G>A), RS1003108042 (9:35101416 T>C), RS1003345347 (9:35099529 C>G,T), RS1003442289 (9:35099921 A>G), RS1004611641 (9:35102491 G>A,C), RS1005042027 (9:35102194 C>T), RS1005286887 (9:35103241 A>G), RS1005605161 (9:35103102 C>A,T)

Disease associations

OMIM: gene MIM:608292 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067176 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	Kd	19.88	nM	CHEMBL3752910
7.70	ED50	19.88	nM	CHEMBL3752910
7.41	Kd	38.58	nM	CHEMBL5653589
7.41	ED50	38.58	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149516: Binding affinity to human STOML2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0199	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149516: Binding affinity to human STOML2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0386	uM

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
bisphenol A	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
chloropicrin	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects reaction, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	affects cotreatment, affects localization, increases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects expression, affects response to substance	1
Paraquat	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	increases expression	1
Selenium	increases expression	1
Sodium Chloride	affects cotreatment, affects localization, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652558	Binding	Binding affinity to human STOML2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2L4	HAP1 STOML2 (-) 1	Cancer cell line	Male
CVCL_E2L5	HAP1 STOML2 (-) 2	Cancer cell line	Male
CVCL_E2L6	HAP1 STOML2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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