SELENOS

Summary

SELENOS (selenoprotein S, HGNC:30396) is a protein-coding gene on chromosome 15q26.3, encoding Selenoprotein S (Q9BQE4). Involved in the degradation process of misfolded endoplasmic reticulum (ER) luminal proteins.

This gene encodes a transmembrane protein that is localized in the endoplasmic reticulum (ER). It is involved in the degradation process of misfolded proteins in the ER, and may also have a role in inflammation control. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3’ UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Two additional phylogenetically conserved stem-loop structures (Stem-loop 1 and Stem-loop 2) in the 3’ UTR of this mRNA have been shown to function as modulators of Sec insertion. An alternatively spliced transcript variant, lacking the SECIS element and encoding a non-Sec containing shorter isoform, has been described for this gene (PMID:23614019).

Source: NCBI Gene 55829 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_018445

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30396
Approved symbol	SELENOS
Name	selenoprotein S
Location	15q26.3
Locus type	gene with protein product
Status	Approved
Aliases	SELS, MGC2553, SBBI8, AD-015, SEPS1
Ensembl gene	ENSG00000131871
Ensembl biotype	protein_coding
OMIM	607918
Entrez	55829

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 4 retained_intron

ENST00000398226, ENST00000526043, ENST00000526049, ENST00000527833, ENST00000528346, ENST00000529968, ENST00000531964, ENST00000534014

RefSeq mRNA: 2 — MANE Select: NM_018445 NM_018445, NM_203472

CCDS: CCDS53979

Canonical transcript exons

ENST00000526049 — 6 exons

Exon	Start	End
ENSE00000703045	101274592	101274681
ENSE00002152201	101277342	101277485
ENSE00002170760	101272191	101272856
ENSE00003490400	101274420	101274495
ENSE00003499614	101275255	101275361
ENSE00003601084	101276541	101276675

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.9831 / max 399.5566, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151816	46.9027	1822
151815	0.0804	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.47	gold quality
upper arm skin	UBERON:0004263	98.52	gold quality
left ventricle myocardium	UBERON:0006566	98.11	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.91	gold quality
jejunal mucosa	UBERON:0000399	97.90	gold quality
cartilage tissue	UBERON:0002418	97.86	gold quality
colonic mucosa	UBERON:0000317	97.72	gold quality
tibialis anterior	UBERON:0001385	97.70	gold quality
parotid gland	UBERON:0001831	97.68	gold quality
rectum	UBERON:0001052	97.58	gold quality
duodenum	UBERON:0002114	97.50	gold quality
body of pancreas	UBERON:0001150	97.48	gold quality
right testis	UBERON:0004534	97.38	gold quality
decidua	UBERON:0002450	97.35	gold quality
left testis	UBERON:0004533	97.34	gold quality
mucosa of transverse colon	UBERON:0004991	97.30	gold quality
placenta	UBERON:0001987	97.00	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.97	gold quality
adult organism	UBERON:0007023	96.82	gold quality
heart right ventricle	UBERON:0002080	96.76	gold quality
myocardium	UBERON:0002349	96.74	gold quality
upper leg skin	UBERON:0004262	96.74	gold quality
pericardium	UBERON:0002407	96.71	gold quality
nasal cavity mucosa	UBERON:0001826	96.62	gold quality
pancreas	UBERON:0001264	96.61	gold quality
seminal vesicle	UBERON:0000998	96.52	gold quality
stromal cell of endometrium	CL:0002255	96.51	gold quality
trachea	UBERON:0003126	96.50	gold quality
synovial joint	UBERON:0002217	96.43	gold quality
calcaneal tendon	UBERON:0003701	96.42	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	106.07
E-CURD-46	yes	67.16
E-HCAD-4	yes	64.85
E-MTAB-9467	yes	57.41
E-HCAD-1	yes	53.27
E-CURD-122	yes	49.32
E-MTAB-8410	yes	43.35
E-HCAD-9	yes	14.79
E-MTAB-10553	yes	12.44
E-HCAD-10	yes	4.45
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, NFKB

miRNA regulators (miRDB)

32 targeting SELENOS, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-3161	98.71	67.14	816
HSA-MIR-12127	97.93	66.67	793
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-10397-5P	97.31	69.06	710
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-8086	97.21	64.13	331
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-6866-5P	96.64	68.06	624
HSA-MIR-6760-3P	96.35	68.31	1001

Literature-anchored findings (GeneRIF, showing 40)

• SELS is regulated by glucose deprivation and endoplasmic reticulum stress. It is a glucose-regulated protein. (PMID:15063746)
• Positive relationship between Tanis mRNA and the acute-phase protein serum amyloid A suggests an interaction between innate immune system responses and Tanis expression in muscle and adipose tissue. (PMID:15161744)
• Derlin-1 interacts with US11, a virally encoded ER protein that specifically targets MHC class I heavy chains for export from the ER, as well as with VIMP, a novel membrane protein that recruits the p97 ATPase and its cofactor (PMID:15215856)
• Regulatory variant in SELS influences inflammatory response to ER stress (PMID:16227999)
• SEPS1 may regulate cytokine production in macrophage cells and there may be a regulatory loop between TNF-alpha, IL-1beta and SEPS1 that plays a key role in control of the inflammatory response (PMID:16574427)
• SEPS1 protein is secreted from hepatoma cells. Fractionation of human serum indicated that SEPS1 was associated with LDL and possibly with VLDL. (PMID:17374524)
• significant association with increased CHD risk in females carrying the minor allele of rs8025174. Another variant, rs7178239, increased the risk for ischemic stroke significantly in females. (PMID:17641917)
• -105G>A polymorphism is not associated with IBD susceptibility and does not contribute to a certain disease phenotype or increased TNF-alpha levels in IBD patients. (PMID:17661913)
• Selenoprotein S -105(adenosine) allele is a non-significant risk factor in young stroke patients from Italy and Germany. (PMID:17880573)
• Six polymorphisms were studied in this gene, and none are associated with type 1 diabetes, rheumatoid arthritis or inflammatory bowel diseases. (PMID:18625033)
• SelS has a role in lipopolysaccharide-induced inflammatory response in hepatoma HepG2 cells (PMID:18675776)
• SelS protein may be involved in insulin resistance in Chinese with type 2 diabetes mellitus (T2DM) by acting as the SAA receptor, thus playing an important role in the development of T2DM and atherosclerosis (PMID:18710632)
• The -105G>A promoter polymorphism of SEPS1 was associated with the intestinal type of gastric cancer. (PMID:19144102)
• Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency. (PMID:19398551)
• beta-ME, also an ER stress agent, could induce cell apoptosis, and SelS may play an important role in protecting cells from apoptosis induced by ER stress in HepG2 cells. (PMID:20114070)
• a role for SELS in the development of metabolic disease, especially in the context of insulin resistance. (PMID:20619427)
• Upregulation of SelS expression in reactive astrocytes reveals a new protective role for SelS against inflammation and endoplasmic reticulum stress that can be relevant to astrocyte function. (PMID:21456042)
• the redox properties observed for recombinant VIMP are compatible with a function as a reductase (PMID:22700979)
• These results suggest a potential role for the SELS region in the development subclinical cardiovascular disease in this sample enriched for type 2 diabetes mellitus. (PMID:23161441)
• Findings suggest that the SEPS1 G-105A polymorphism contributes to the risk of developing SPTB in a Chinese population. (PMID:23776519)
• Our results indicated that the rs12910524 in the Tanis gene was associated with triglyceride concentrations in subjects without diabetes in China. (PMID:23829426)
• Data suggest that selenocysteine allows selenoprotein S (SelS, VIMP) to sustain activity under oxidative stress. (PMID:23914919)
• Selenoprotein S is a marker but not a regulator of endoplasmic reticulum stress in intestinal epithelial cells in inflammatory bowel diseases. (PMID:24275540)
• Existence of a link between SEPS1 promoter genetic variation and Hashimoto thyroiditis risk. (PMID:24471570)
• that SEPS1 may protect mice against LPS-induced sepsis and organ damage. Therefore, SEPS1 may be a new target to resolve LPS-induced sepsis. (PMID:24573439)
• Pro(178) and Pro(183) of SelS play important roles in the translocation of p97(VCP) to the ER membrane and protect cells from ER stress (PMID:24700463)
• Although VIMP can interact with CLIMP-63 and Syn5L, it does not interact with MT-binding ER proteins (such as Reep1) that shape the tubular smooth ER (PMID:25008318)
• SNP rs4965814 of SELS may affect the susceptibility to ischemic stroke. (PMID:25390504)
• The SEPS1 -105G>A is associated with an increased risk of Kashin-Beck disease and influences the expression of PI3K/Akt signaling pathway in Kashin-Beck disease patients (PMID:25433273)
• Potential roles of the SEPS1 gene in the pathogenesis and etiology of Hashimoto’s thyroiditis. (PMID:26016409)
• SEPS1 may be a potential gene marker for disease diagnosis and prognosis. (PMID:26382012)
• interaction between SelK and p97(VCP) is SelS-dependent, and the resulting ERAD complex (SelS-p97(VCP)-SelK) plays an important role in ERAD and ER stress (PMID:26504085)
• regulating liver and serum Selenoprotein S levels might become a new strategy for the prevention and treatment of DM and its macrovascular complications (PMID:27121097)
• In these studies found that SelS increases in negative correlation with tau phosphorylation in brain. (PMID:27802219)
• The results suggest that SelS is required for C99 degradation through endoplasmic reticulum-associated degradation, resulting in inhibition of amyloid beta production. (PMID:28315680)
• the Role of VIMP in Endoplasmic Reticulum-Associated Degradation of CFTRDeltaF508 (PMID:29555962)
• The levels of SelS and SelK were decreased during adipocyte differentiation and were inversely related to the levels of peroxisome proliferator-activated receptor gamma (PPARgamma), a central regulator of adipogenesis. (PMID:30082770)
• The present study suggested that genetic polymorphisms of SelS were associated with Type 2 diabetes in a Chinese population (PMID:30413610)
• SEPS1 gene polymorphism is associated with diabetic nephropathy. (PMID:31265177)
• Interaction of Genetic Variations in NFE2L2 and SELENOS Modulates the Risk of Hashimoto’s Thyroiditis. (PMID:31426718)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Selenos	ENSMUSG00000075701
rattus_norvegicus	Selenos	ENSRNOG00000012576

Protein

Protein identifiers

Selenoprotein S — Q9BQE4 (reviewed: Q9BQE4)

Alternative names: VCP-interacting membrane protein

All UniProt accessions (3): A0A182DWI4, E9PN30, Q9BQE4

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the degradation process of misfolded endoplasmic reticulum (ER) luminal proteins. Participates in the transfer of misfolded proteins from the ER to the cytosol, where they are destroyed by the proteasome in a ubiquitin-dependent manner. Probably acts by serving as a linker between DERL1, which mediates the retrotranslocation of misfolded proteins into the cytosol, and the ATPase complex VCP, which mediates the translocation and ubiquitination.

Subunit / interactions. Interacts with DERL1 and (via VIM motif) with VCP, suggesting that it forms a membrane complex with DERL1 that serves as a receptor for VCP. Also interacts with DERL2, DERL3 and SELENOK. The SELENOK-SELENOS complex interacts with VCP. Interacts with CCDC47.

Subcellular location. Endoplasmic reticulum membrane. Cytoplasm.

Post-translational modifications. Truncated SELENOS proteins produced by failed UGA/Sec decoding are ubiquitinated by the CRL2(KLHDC2) and CRL2(KLHDC3) complexes, which recognizes the glycine (Gly) at the C-terminus of truncated SELENOS proteins. Truncated SELENOS proteins produced by failed UGA/Sec decoding are also ubiquitinated by the CRL5(KLHDC1) complex.

Similarity. Belongs to the selenoprotein S family.

RefSeq proteins (2): NP_060915, NP_982298 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009703	Selenoprotein_S	Family

Pfam: PF06936

UniProt features (10 total): region of interest 2, helix 2, chain 1, transmembrane region 1, compositionally biased region 1, non-standard amino acid 1, modified residue 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2Q2F	X-RAY DIFFRACTION	1.5
5KIU	X-RAY DIFFRACTION	2.2
6DO4	X-RAY DIFFRACTION	2.2
5KIY	X-RAY DIFFRACTION	2.79
5KIW	X-RAY DIFFRACTION	3.41

Predicted structure (AlphaFold)

No AlphaFold model available for Q9BQE4 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (1): 140

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-8852135	Protein ubiquitination

MSigDB gene sets: 321 (showing top): GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_ENDOPLASMIC_RETICULUM_TO_CYTOSOL_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP

GO Biological Process (23): negative regulation of acute inflammatory response to antigenic stimulus (GO:0002865), regulation of gluconeogenesis (GO:0006111), ER overload response (GO:0006983), response to glucose (GO:0009749), endoplasmic reticulum unfolded protein response (GO:0030968), retrograde protein transport, ER to cytosol (GO:0030970), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), cellular response to insulin stimulus (GO:0032869), cellular response to oxidative stress (GO:0034599), ERAD pathway (GO:0036503), establishment of protein localization (GO:0045184), cell redox homeostasis (GO:0045454), negative regulation of glycogen biosynthetic process (GO:0045719), negative regulation of D-glucose import across plasma membrane (GO:0046325), negative regulation of inflammatory response (GO:0050728), response to redox state (GO:0051775), cellular response to lipopolysaccharide (GO:0071222), regulation of nitric oxide metabolic process (GO:0080164), negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway (GO:1902236), negative regulation of macrophage apoptotic process (GO:2000110), intracellular protein transport (GO:0006886), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (6): antioxidant activity (GO:0016209), enzyme binding (GO:0019899), signaling receptor activity (GO:0038023), ATPase binding (GO:0051117), ubiquitin-specific protease binding (GO:1990381), protein binding (GO:0005515)

GO Cellular Component (10): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytoplasmic microtubule (GO:0005881), plasma membrane (GO:0005886), very-low-density lipoprotein particle (GO:0034361), low-density lipoprotein particle (GO:0034362), Derlin-1-VIMP complex (GO:0036502), Derlin-1 retrotranslocation complex (GO:0036513), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Protein ubiquitination	1
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to endoplasmic reticulum stress	3
cytoplasm	2
endoplasmic reticulum membrane	2
membrane protein complex	2
endoplasmic reticulum protein-containing complex	2
cellular anatomical structure	2
acute inflammatory response to antigenic stimulus	1
negative regulation of acute inflammatory response	1
negative regulation of inflammatory response to antigenic stimulus	1
regulation of acute inflammatory response to antigenic stimulus	1
gluconeogenesis	1
regulation of glucose metabolic process	1
regulation of carbohydrate biosynthetic process	1
ER-nucleus signaling pathway	1
cellular response to biotic stimulus	1
response to hexose	1
cellular response to unfolded protein	1
intracellular signal transduction	1
protein exit from endoplasmic reticulum	1
ERAD pathway	1
endoplasmic reticulum to cytosol transport	1
negative regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
response to insulin	1
cellular response to peptide hormone stimulus	1
response to oxidative stress	1
cellular response to chemical stress	1
proteasomal protein catabolic process	1
response to chemical	1
establishment of localization	1
cellular homeostasis	1
glycogen biosynthetic process	1
regulation of glycogen biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of glycogen metabolic process	1
negative regulation of D-glucose transmembrane transport	1

Protein interactions and networks

STRING

974 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SELENOS	SELENOK	Q9Y6D0	961
SELENOS	VCP	P55072	920
SELENOS	SELENOF	O60613	912
SELENOS	SELENOT	P62341	912
SELENOS	DERL2	Q9GZP9	874
SELENOS	SEL1L	Q9UBV2	873
SELENOS	SELENOM	Q8WWX9	873
SELENOS	SELENON	Q9NZV5	872
SELENOS	SELENOO	Q9BVL4	872
SELENOS	SELENOI	Q9C0D9	826
SELENOS	SELENOH	Q8IZQ5	822
SELENOS	SEPHS2	Q99611	815
SELENOS	SELENOV	P59797	804
SELENOS	MSRB1	Q9NZV6	802
SELENOS	SELENOW	P63302	802

IntAct

57 interactions, top by confidence:

A	B	Type	Score
KLHDC2	CUL2	psi-mi:“MI:0914”(association)	0.730
VCP	UBXN8	psi-mi:“MI:0914”(association)	0.690
SELENOS	rep	psi-mi:“MI:0915”(physical association)	0.660
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
SELENOS	Vcp	psi-mi:“MI:0914”(association)	0.610
SELENOS	Vcp	psi-mi:“MI:0915”(physical association)	0.610
Vcp	SELENOS	psi-mi:“MI:0915”(physical association)	0.610
Vcp	SELENOS	psi-mi:“MI:0403”(colocalization)	0.610
APOA5	SELENOS	psi-mi:“MI:0915”(physical association)	0.560
SELENOS		psi-mi:“MI:0915”(physical association)	0.550
KLHDC2	PFDN1	psi-mi:“MI:0914”(association)	0.530
rep	AGPS	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
SELENOS	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
SELENOS	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
APOB	APOA1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
DERL2	ARL6IP5	psi-mi:“MI:0914”(association)	0.350
FAF2	ERLIN1	psi-mi:“MI:0914”(association)	0.350
SELENOS	UBXN8	psi-mi:“MI:0914”(association)	0.350
rep	CEBPZOS	psi-mi:“MI:0914”(association)	0.350
SELENOS	Vcp	psi-mi:“MI:0914”(association)	0.350
DERL1	Vcp	psi-mi:“MI:0403”(colocalization)	0.350
VCL	UBXN8	psi-mi:“MI:0914”(association)	0.350
RUSF1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
SCN4A	C2CD4B	psi-mi:“MI:0914”(association)	0.350

BioGRID (137): VIMP (Affinity Capture-MS), SELK (Affinity Capture-MS), KLHDC2 (Affinity Capture-MS), UBXN8 (Affinity Capture-MS), DERL1 (Affinity Capture-MS), DERL2 (Affinity Capture-MS), VCP (Affinity Capture-MS), UBE4A (Affinity Capture-MS), FAF2 (Affinity Capture-MS), VIMP (Affinity Capture-MS), VIMP (Affinity Capture-Western), VCP (Reconstituted Complex), CKAP4 (Affinity Capture-Western), VIMP (Reconstituted Complex), VCP (Affinity Capture-Western)

ESM2 similar proteins: A2A8U2, A6H773, A6QPI4, D4A6L0, E1BBQ2, O60232, P54098, Q05B67, Q08BI9, Q148E1, Q2KI76, Q2KJ58, Q2NL34, Q32Q90, Q4R4I0, Q5C9Z4, Q5RE99, Q5SNT2, Q5T6X4, Q5T848, Q5VUE5, Q5XIJ4, Q5ZLJ4, Q6DVA0, Q6P3B9, Q7T076, Q80YR4, Q86UK7, Q8C419, Q8CEG5, Q8IYL2, Q8N0V3, Q8NC56, Q8TBN0, Q8VDV3, Q8VE22, Q8VHV8, Q921N7, Q96IL0, Q96ND0

Diamond homologs: F1SR90, Q0VFV6, Q2KI76, Q5I030, Q68EU0, Q6AZH0, Q8VHV8, Q9BCZ4, Q9BQE4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SELENOS	“up-regulates activity”	DERL1	binding
SELENOS	“up-regulates activity”	VCP	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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
Defective CFTR causes cystic fibrosis	5	28.2×	2e-04
ABC-family protein mediated transport	6	18.7×	2e-04
Cellular responses to stress	6	5.7×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	6	22.2×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

883 predictions. Top by Δscore:

Variant	Effect	Δscore
15:101272773:AG:A	donor_gain	1.0000
15:101272774:G:C	donor_gain	1.0000
15:101274414:GCTTA:G	donor_loss	1.0000
15:101274415:CTTAC:C	donor_loss	1.0000
15:101274416:TTA:T	donor_loss	1.0000
15:101274417:TA:T	donor_loss	1.0000
15:101274418:A:AC	donor_gain	1.0000
15:101274418:ACCT:A	donor_gain	1.0000
15:101274419:C:CC	donor_gain	1.0000
15:101274419:C:CT	donor_loss	1.0000
15:101274419:CCTC:C	donor_gain	1.0000
15:101274421:T:TA	donor_gain	1.0000
15:101274682:C:CC	acceptor_gain	1.0000
15:101275249:TCATA:T	donor_loss	1.0000
15:101275251:ATAC:A	donor_loss	1.0000
15:101275252:TA:T	donor_loss	1.0000
15:101275253:A:AC	donor_gain	1.0000
15:101275253:AC:A	donor_loss	1.0000
15:101275254:C:CA	donor_gain	1.0000
15:101275254:CTT:C	donor_gain	1.0000
15:101275254:CTTG:C	donor_gain	1.0000
15:101275254:CTTGT:C	donor_gain	1.0000
15:101275268:T:A	donor_gain	1.0000
15:101275273:ATG:A	donor_gain	1.0000
15:101275278:TTTCA:T	donor_gain	1.0000
15:101275357:AGGTT:A	acceptor_gain	1.0000
15:101275358:GGTT:G	acceptor_gain	1.0000
15:101275359:GTT:G	acceptor_gain	1.0000
15:101275360:TT:T	acceptor_gain	1.0000
15:101275362:C:CC	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000440146 (15:101275485 T>C), RS1000649519 (15:101279378 G>T), RS1000774589 (15:101274094 G>C,T), RS1001102539 (15:101278059 C>T), RS1001329522 (15:101275043 T>C), RS1001353521 (15:101273998 T>G), RS1001656104 (15:101274791 C>A,G), RS1002015166 (15:101270999 C>T), RS1002107470 (15:101278915 G>A,T), RS1002904357 (15:101276355 T>A,C), RS1002925211 (15:101273473 C>T), RS1003241425 (15:101277152 G>A), RS1003408038 (15:101273681 G>A), RS1003685393 (15:101277692 G>A,C,T), RS1003780293 (15:101277603 C>A,G)

Disease associations

OMIM: gene MIM:607918 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002183_3	Relative hand skill in reading disability	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009902	handedness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	5
bisphenol A	affects expression, decreases expression, decreases methylation	3
Tobacco Smoke Pollution	affects expression, increases expression	3
Tunicamycin	increases expression	3
Cyclosporine	increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cisplatin	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
lasiocarpine	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
W 7	affects cotreatment, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	increases phosphorylation	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
pinostrobin	increases expression	1
fenpyroximate	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
picoxystrobin	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Diuron	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Ozone	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2EZ	Abcam HeLa SELENOS KO	Cancer cell line	Female
CVCL_E2NP	HAP1 VIMP (-) 2	Cancer cell line	Male
CVCL_XV01	HAP1 VIMP (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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