SELENOM

Summary

SELENOM (selenoprotein M, HGNC:30397) is a protein-coding gene on chromosome 22q12.2, encoding Selenoprotein M (Q8WWX9). May function as a thiol-disulfide oxidoreductase that participates in disulfide bond formation.

The protein encoded by this gene belongs to the selenoprotein M/SEP15 family. The exact function of this protein is not known. It is localized in the perinuclear region, is highly expressed in the brain, and may be involved in neurodegenerative disorders. Transgenic mice with targeted deletion of this gene exhibit increased weight gain, suggesting a role for this gene in the regulation of body weight and energy metabolism. 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.

Source: NCBI Gene 140606 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_080430

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30397
Approved symbol	SELENOM
Name	selenoprotein M
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	SELM, SEPM
Ensembl gene	ENSG00000198832
Ensembl biotype	protein_coding
OMIM	610918
Entrez	140606

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000400299, ENST00000402395, ENST00000460642, ENST00000465447, ENST00000465536, ENST00000469262, ENST00000490967, ENST00000491958, ENST00000495533

RefSeq mRNA: 1 — MANE Select: NM_080430 NM_080430

CCDS: CCDS43003

Canonical transcript exons

ENST00000400299 — 5 exons

Exon	Start	End
ENSE00001550211	31107377	31107568
ENSE00003467983	31104777	31105128
ENSE00003485451	31105658	31105692
ENSE00003494089	31105208	31105286
ENSE00003618990	31105930	31105965

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 99.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 97.2488 / max 984.9370, expressed in 1738 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193671	91.4113	1737
193670	5.2787	1096
193668	0.2860	133
193669	0.2728	143

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	99.66	gold quality
right coronary artery	UBERON:0001625	99.57	gold quality
popliteal artery	UBERON:0002250	99.55	gold quality
tibial artery	UBERON:0007610	99.55	gold quality
left coronary artery	UBERON:0001626	99.53	gold quality
body of uterus	UBERON:0009853	99.53	gold quality
aorta	UBERON:0000947	99.52	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.51	gold quality
ascending aorta	UBERON:0001496	99.50	gold quality
thoracic aorta	UBERON:0001515	99.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.50	gold quality
lower esophagus	UBERON:0013473	99.49	gold quality
left uterine tube	UBERON:0001303	99.47	gold quality
coronary artery	UBERON:0001621	99.47	gold quality
descending thoracic aorta	UBERON:0002345	99.47	gold quality
endocervix	UBERON:0000458	99.44	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.25	gold quality
decidua	UBERON:0002450	99.14	gold quality
saphenous vein	UBERON:0007318	99.13	gold quality
adenohypophysis	UBERON:0002196	99.11	gold quality
myometrium	UBERON:0001296	99.01	gold quality
right ovary	UBERON:0002118	98.97	gold quality
pituitary gland	UBERON:0000007	98.95	gold quality
urethra	UBERON:0000057	98.92	gold quality
left lobe of thyroid gland	UBERON:0001120	98.84	gold quality
left ovary	UBERON:0002119	98.83	gold quality
right lobe of thyroid gland	UBERON:0001119	98.73	gold quality
tibial nerve	UBERON:0001323	98.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.65	gold quality
right atrium auricular region	UBERON:0006631	98.39	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-HCAD-36	yes	1879.85
E-MTAB-8142	yes	1273.97
E-CURD-88	yes	946.66
E-MTAB-6701	yes	137.36
E-GEOD-75688	yes	103.10
E-HCAD-1	yes	96.19
E-MTAB-10287	yes	94.02
E-MTAB-8410	yes	61.36
E-HCAD-4	yes	56.06
E-CURD-46	yes	45.74
E-CURD-114	yes	34.96
E-HCAD-5	yes	34.14
E-GEOD-135922	yes	33.52
E-MTAB-6678	yes	27.26
E-GEOD-125970	yes	19.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting SELENOM, 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-4692	100.00	67.32	2066
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-1298-5P	95.96	64.81	573
HSA-MIR-12115	94.19	66.37	738
HSA-MIR-1247-3P	83.69	63.18	99

Literature-anchored findings (GeneRIF, showing 5)

• As Gal-1 plays important roles in preventing neurodegeneration and promoting neuroprotection in the brain, the interaction between SelM’ and Gal-1 displays a new direction for studying the biological function of SelM in the human brain. (PMID:24284396)
• The aim of this study has been to analyze the structure-function relationships of SelM. (PMID:24332979)
• results evidence for the first time an increase of SELM expression in HCC liver tissues, and its gradual expression raise associated with an increased malignancy grade. (PMID:25578973)
• Selenoprotein M stimulates the proliferative and metastatic capacities of renal cell carcinoma through activating the PI3K/AKT/mTOR pathway. (PMID:31274247)
• Methylseleninic acid in both cancer cell lines increased the SELM gene expression; the most pronounced effect was observed when fibrosarcoma cells were treated with 10 microM MSA (the expression of the hSelm gene increased almost 4 times). (PMID:31768845)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	selenom	ENSDARG00000051957
mus_musculus	Selenom	ENSMUSG00000075702
rattus_norvegicus	Selenom	ENSRNOG00000061231
drosophila_melanogaster	CG7484	FBGN0036745
caenorhabditis_elegans		WBGENE00022297

Paralogs (1): SELENOF (ENSG00000183291)

Protein

Protein identifiers

Selenoprotein M — Q8WWX9 (reviewed: Q8WWX9)

All UniProt accessions (1): Q8WWX9

UniProt curated annotations — full annotation on UniProt →

Function. May function as a thiol-disulfide oxidoreductase that participates in disulfide bond formation.

Subcellular location. Cytoplasm. Perinuclear region. Endoplasmic reticulum. Golgi apparatus.

Tissue specificity. Widely expressed.

Similarity. Belongs to the selenoprotein M/F family.

RefSeq proteins (1): NP_536355* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR014912	Sep15_SelM_dom	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR038219	Sep15/SelM_sf	Homologous_superfamily
IPR039992	Sep15_SelM	Family

Pfam: PF08806

UniProt features (6 total): active site 2, signal peptide 1, chain 1, non-standard amino acid 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q8WWX9 — 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.

Catalytic / active sites (2): 45 (nucleophile); 48 (nucleophile)

Post-translational modifications (1): 45–48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 169 (showing top): GOBP_GROWTH, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, TAL1ALPHAE47_01, CHANDRAN_METASTASIS_DN, GOBP_CELL_CELL_SIGNALING, COUP_01, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, YY1_02, HNF4_DR1_Q3, GOBP_MULTICELLULAR_ORGANISM_GROWTH, GOBP_SECRETION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, HNF4_01, LIAO_METASTASIS

GO Biological Process (5): response to selenium ion (GO:0010269), multicellular organism growth (GO:0035264), corticosterone secretion (GO:0035934), hormone metabolic process (GO:0042445), adipose tissue development (GO:0060612)

GO Molecular Function (2): oxidoreductase activity (GO:0016491), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
response to chemical	1
multicellular organismal process	1
developmental growth	1
organic hydroxy compound transport	1
glucocorticoid secretion	1
metabolic process	1
regulation of hormone levels	1
animal organ development	1
connective tissue development	1
catalytic activity	1
binding	1
endoplasmic reticulum	1
intracellular organelle lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

258 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SELENOM	SELENOT	P62341	893
SELENOM	SELENOF	O60613	892
SELENOM	SELENOK	Q9Y6D0	874
SELENOM	SELENOS	Q9BQE4	873
SELENOM	SELENON	Q9NZV5	857
SELENOM	SELENOO	Q9BVL4	856
SELENOM	SELENOH	Q8IZQ5	801
SELENOM	SEPHS2	Q99611	793
SELENOM	SELENOI	Q9C0D9	778
SELENOM	SELENOV	P59797	775
SELENOM	MSRB1	Q9NZV6	740
SELENOM	SELENOW	P63302	740
SELENOM	TXNRD3	Q86VQ6	740
SELENOM	TXNRD2	Q9NNW7	737
SELENOM	SELENOP	P49908	736

IntAct

48 interactions, top by confidence:

A	B	Type	Score
MTUS2	SELENOM	psi-mi:“MI:0915”(physical association)	0.560
SELENOM	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
SELENOM		psi-mi:“MI:0915”(physical association)	0.560
SELENOM	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	SELENOM	psi-mi:“MI:0915”(physical association)	0.560
	SELENOM	psi-mi:“MI:0915”(physical association)	0.560
SELENOM	MDFI	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	SELENOM	psi-mi:“MI:0915”(physical association)	0.560
SELENOM	SGTB	psi-mi:“MI:0915”(physical association)	0.560
HSPE1	SELENOM	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	SELENOM	psi-mi:“MI:0915”(physical association)	0.560
SELENOM	REEP4	psi-mi:“MI:0915”(physical association)	0.560
SELENOM	SEC11C	psi-mi:“MI:0915”(physical association)	0.560
NIPA1	SELENOM	psi-mi:“MI:0915”(physical association)	0.560
NENF	BLVRB	psi-mi:“MI:0914”(association)	0.530
CYB5D2	ABLIM1	psi-mi:“MI:0914”(association)	0.530
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
NAT10	HERC2	psi-mi:“MI:0914”(association)	0.350
ASPN	ITIH2	psi-mi:“MI:0914”(association)	0.350
UFL1	UFM1	psi-mi:“MI:0914”(association)	0.350
NME3	VWA8	psi-mi:“MI:0914”(association)	0.350
TTR	PALM	psi-mi:“MI:0914”(association)	0.350
SELENOM	MDFI	psi-mi:“MI:0915”(physical association)	0.000
SELENOM	KRTAP1-3	psi-mi:“MI:0915”(physical association)	0.000
SELENOM	SGTB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): SELM (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), SELM (Affinity Capture-MS), SELM (Affinity Capture-MS), SELM (Co-fractionation), RAB11FIP5 (Co-fractionation), SELM (Two-hybrid), SELM (Two-hybrid), SELM (Two-hybrid), SELM (Two-hybrid), SELM (Two-hybrid), SELM (Two-hybrid), SELM (Two-hybrid), KRTAP12-3 (Two-hybrid)

ESM2 similar proteins: A1Z623, A2SXS5, A8YXY3, F1LQY6, O02718, O19011, O60613, P01137, P04202, P07200, P09533, P11456, P18341, P50747, P54831, Q08BI9, Q0P5I0, Q1LZ96, Q2KIJ6, Q2TBX5, Q38HS2, Q3UHE1, Q3UX43, Q58CS8, Q5C9Z4, Q5R812, Q5RB75, Q6IEE6, Q6PCX7, Q6X4M2, Q802F3, Q802G7, Q8BJQ9, Q8IVD9, Q8NC56, Q8R1N4, Q8R1T1, Q8TDX6, Q8VHC3, Q8WUX9

Diamond homologs: G4WAW9, Q6GP98, Q802G7, Q8VHC3, Q8WWX9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1450 predictions. Top by Δscore:

Variant	Effect	Δscore
22:31105124:ATGCG:A	acceptor_gain	1.0000
22:31105125:TGCG:T	acceptor_gain	1.0000
22:31105126:GCG:G	acceptor_gain	1.0000
22:31105127:CG:C	acceptor_gain	1.0000
22:31105127:CGC:C	acceptor_gain	1.0000
22:31105129:C:CC	acceptor_gain	1.0000
22:31105130:T:C	acceptor_loss	1.0000
22:31105925:CTCA:C	donor_loss	1.0000
22:31105928:A:AC	donor_gain	1.0000
22:31105928:ACCT:A	donor_gain	1.0000
22:31105929:C:A	donor_loss	1.0000
22:31105929:C:CC	donor_gain	1.0000
22:31105929:CCT:C	donor_gain	1.0000
22:31105929:CCTC:C	donor_gain	1.0000
22:31105931:T:TA	donor_gain	1.0000
22:31105961:CAGGT:C	acceptor_gain	1.0000
22:31105966:C:CC	acceptor_gain	1.0000
22:31107685:T:TA	donor_gain	1.0000
22:31107717:C:A	donor_gain	1.0000
22:31107740:T:A	donor_gain	1.0000
22:31105135:C:CT	acceptor_gain	0.9900
22:31105136:G:T	acceptor_gain	0.9900
22:31105202:CCTCA:C	donor_loss	0.9900
22:31105203:CTCAC:C	donor_loss	0.9900
22:31105204:TCACC:T	donor_loss	0.9900
22:31105205:CACC:C	donor_loss	0.9900
22:31105206:ACC:A	donor_loss	0.9900
22:31105207:CC:C	donor_loss	0.9900
22:31105287:C:CC	acceptor_gain	0.9900
22:31105296:G:C	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000329869 (22:31106739 T>C,G), RS1000942217 (22:31104743 A>C,G), RS1001835513 (22:31107023 A>C,G,T), RS1002377514 (22:31106815 G>A), RS1002653855 (22:31106783 T>C), RS1002769939 (22:31107146 G>A), RS1002925659 (22:31108243 C>A,T), RS1003246024 (22:31108502 G>A), RS1003660803 (22:31108250 A>C,G), RS1003766932 (22:31108511 G>T), RS1005699904 (22:31107038 G>T), RS1005769921 (22:31108210 G>A), RS1006236605 (22:31107842 G>A), RS1006731565 (22:31108701 T>C), RS1006822775 (22:31107791 C>A,G,T)

Disease associations

OMIM: gene MIM:610918 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST009391_609	Metabolite levels	1.000000e-07
GCST009391_666	Metabolite levels	2.000000e-06
GCST010135_20	Oily fish consumption	3.000000e-10
GCST010135_5	Oily fish consumption	1.000000e-15
GCST010140_12	Pork consumption	3.000000e-10
GCST010140_49	Pork consumption	1.000000e-15
GCST010142_11	Fish- and plant-related diet	1.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009793	isoleucine measurement
EFO:0009770	leucine measurement
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Estradiol	affects cotreatment, increases expression, decreases expression	3
trichostatin A	affects cotreatment, decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
ginger extract	affects cotreatment, affects expression, increases abundance	1
bufotalin	decreases expression	1
bisphenol A	affects expression, increases abundance, affects cotreatment	1
trimellitic anhydride	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	increases expression	1
entinostat	increases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Acetaminophen	affects response to substance	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases methylation	1
Aspirin	increases expression	1
Cytarabine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1

Clinical trials (associated diseases)

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