SMCO2

Summary

SMCO2 (single-pass membrane protein with coiled-coil domains 2, HGNC:34448) is a protein-coding gene on chromosome 12p11.23, encoding Single-pass membrane and coiled-coil domain-containing protein 2 (A6NFE2).

Predicted to be located in membrane.

Source: NCBI Gene 341346 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 56 total
• MANE Select transcript: NM_001395208

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34448
Approved symbol	SMCO2
Name	single-pass membrane protein with coiled-coil domains 2
Location	12p11.23
Locus type	gene with protein product
Status	Approved
Aliases	LOC341346
Ensembl gene	ENSG00000165935
Ensembl biotype	protein_coding
Entrez	341346

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000298876, ENST00000535986, ENST00000538647, ENST00000541168, ENST00000543991, ENST00000698358

RefSeq mRNA: 3 — MANE Select: NM_001395208 NM_001145010, NM_001387218, NM_001395208

CCDS: CCDS44852, CCDS91667

Canonical transcript exons

ENST00000535986 — 9 exons

Exon	Start	End
ENSE00001098242	27474786	27474913
ENSE00001188905	27488460	27488547
ENSE00001188921	27501923	27502185
ENSE00001239019	27494300	27494356
ENSE00001322195	27472776	27472875
ENSE00002273419	27470622	27470765
ENSE00003544813	27475582	27475731
ENSE00003610983	27495680	27495855
ENSE00003973403	27446736	27446825

Expression profiles

Bgee: expression breadth ubiquitous, 120 present calls, max score 91.46.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.46	gold quality
lower esophagus mucosa	UBERON:0035834	84.25	gold quality
esophagus mucosa	UBERON:0002469	67.84	gold quality
superior frontal gyrus	UBERON:0002661	63.18	gold quality
primary visual cortex	UBERON:0002436	61.26	gold quality
skin of leg	UBERON:0001511	58.74	gold quality
zone of skin	UBERON:0000014	58.55	gold quality
esophagus	UBERON:0001043	58.39	gold quality
skin of abdomen	UBERON:0001416	58.39	gold quality
Brodmann (1909) area 9	UBERON:0013540	58.18	gold quality
vermiform appendix	UBERON:0001154	58.16	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	57.97	gold quality
anterior cingulate cortex	UBERON:0009835	57.75	gold quality
islet of Langerhans	UBERON:0000006	57.55	gold quality
vagina	UBERON:0000996	57.37	gold quality
right frontal lobe	UBERON:0002810	57.00	gold quality
body of stomach	UBERON:0001161	56.84	gold quality
descending thoracic aorta	UBERON:0002345	55.08	gold quality
stomach	UBERON:0000945	55.03	gold quality
mucosa of transverse colon	UBERON:0004991	54.92	gold quality
corpus callosum	UBERON:0002336	54.29	gold quality
minor salivary gland	UBERON:0001830	54.18	gold quality
cerebral cortex	UBERON:0000956	53.95	gold quality
ascending aorta	UBERON:0001496	53.34	gold quality
right lobe of liver	UBERON:0001114	53.25	gold quality
thoracic aorta	UBERON:0001515	53.20	gold quality
hypothalamus	UBERON:0001898	52.65	gold quality
cerebellar cortex	UBERON:0002129	52.47	gold quality
cerebellum	UBERON:0002037	52.41	gold quality
cerebellar hemisphere	UBERON:0002245	52.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.24

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Smco2	ENSMUSG00000030292
rattus_norvegicus	Smco2	ENSRNOG00000026883

Paralogs (2): TMCO5A (ENSG00000166069), CCDC188 (ENSG00000234409)

Protein

Protein identifiers

Single-pass membrane and coiled-coil domain-containing protein 2 — A6NFE2 (reviewed: A6NFE2)

All UniProt accessions (3): A0A8V8TM60, A6NFE2, J3KNC3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (3): NP_001138482, NP_001374147, NP_001382137* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026617	SMCO2/5	Family

UniProt features (12 total): sequence conflict 7, chain 1, transmembrane region 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-A6NFE2-F1	59.65	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

162 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMCO2	PPFIBP1	Q86W92	692
SMCO2	BMAL2	Q8WYA1	641
SMCO2	CDRT15	Q96T59	600
SMCO2	STK38L	Q9Y2H1	579
SMCO2	CXorf65	A6NEN9	513
SMCO2	CDRT4	Q8N9R6	507
SMCO2	TMEM167A	Q8TBQ9	475
SMCO2	CCDC90B	Q9GZT6	471
SMCO2	TVP23B	Q9NYZ1	448
SMCO2	TVP23C	Q96ET8	447
SMCO2	SMCO1	Q147U7	447
SMCO2	A0A0A6YYB9	A0A0A6YYB9	446
SMCO2	ARRDC5	A6NEK1	435
SMCO2	C14orf132	Q9NPU4	417
SMCO2	OSBPL8	Q9BZF1	410

IntAct

0 interactions, top by confidence:

BioGRID (3): SMCO2 (Positive Genetic), EEF1G (Cross-Linking-MS (XL-MS)), SMCO2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVN3, A0A482APM8, A1KXM5, A4H257, A4H258, A4H259, A4H260, A6H7F9, A6NFE2, A6NHS7, A7KBS4, E9Q7F5, O74981, O75969, P09258, P09558, P19442, P22575, P80195, P88825, Q00997, Q04547, Q05100, Q2LCV6, Q2M2T8, Q30KK0, Q5NRP9, Q5QR91, Q5RAW4, Q5RBQ2, Q5RII3, Q6AXV6, Q6AXY9, Q6UW49, Q77NN4, Q7Z9I5, Q80YD3, Q810S2, Q8N4C9, Q95LJ2

Diamond homologs: A6NFE2, Q95JR4, Q9DA21

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1522 predictions. Top by Δscore:

Variant	Effect	Δscore
12:27470763:GGA:G	donor_gain	1.0000
12:27470764:GAG:G	donor_gain	1.0000
12:27474769:A:AG	acceptor_gain	1.0000
12:27474770:T:G	acceptor_gain	1.0000
12:27474772:A:AG	acceptor_gain	1.0000
12:27474773:T:G	acceptor_gain	1.0000
12:27474775:A:AG	acceptor_gain	1.0000
12:27474776:T:G	acceptor_gain	1.0000
12:27474781:ACCAG:A	acceptor_gain	1.0000
12:27474785:GGGT:G	acceptor_gain	1.0000
12:27474909:GAACT:G	donor_gain	1.0000
12:27474910:AACT:A	donor_gain	1.0000
12:27474911:ACT:A	donor_gain	1.0000
12:27474911:ACTGT:A	donor_loss	1.0000
12:27474912:CT:C	donor_gain	1.0000
12:27474912:CTGT:C	donor_loss	1.0000
12:27474913:TG:T	donor_loss	1.0000
12:27474914:G:C	donor_loss	1.0000
12:27474914:G:GG	donor_gain	1.0000
12:27474915:TAAG:T	donor_loss	1.0000
12:27495676:TCAG:T	acceptor_loss	1.0000
12:27495677:CA:C	acceptor_loss	1.0000
12:27495678:A:AG	acceptor_gain	1.0000
12:27495678:AG:A	acceptor_gain	1.0000
12:27495678:AGGA:A	acceptor_loss	1.0000
12:27495679:G:GT	acceptor_gain	1.0000
12:27495679:GG:G	acceptor_gain	1.0000
12:27495679:GGA:G	acceptor_gain	1.0000
12:27495679:GGAC:G	acceptor_gain	1.0000
12:27495679:GGACC:G	acceptor_gain	1.0000

AlphaMissense

2301 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:27502083:T:C	F332L	0.860
12:27502085:C:A	F332L	0.860
12:27502085:C:G	F332L	0.860
12:27502008:T:C	F307L	0.839
12:27502010:T:A	F307L	0.839
12:27502010:T:G	F307L	0.839
12:27502014:T:C	F309L	0.774
12:27502016:T:A	F309L	0.774
12:27502016:T:G	F309L	0.774
12:27501981:T:C	C298R	0.722
12:27501951:T:C	F288L	0.685
12:27501953:T:A	F288L	0.685
12:27501953:T:G	F288L	0.685
12:27488483:T:C	L179P	0.683
12:27470725:T:C	F32L	0.680
12:27470727:T:A	F32L	0.680
12:27470727:T:G	F32L	0.680
12:27475618:G:C	W133C	0.680
12:27475618:G:T	W133C	0.680
12:27501972:G:A	G295R	0.678
12:27501972:G:C	G295R	0.678
12:27501926:A:C	K279N	0.659
12:27501926:A:T	K279N	0.659
12:27501942:T:C	F285L	0.646
12:27501944:C:A	F285L	0.646
12:27501944:C:G	F285L	0.646
12:27475616:T:A	W133R	0.641
12:27475616:T:C	W133R	0.641
12:27472864:T:C	F75L	0.640
12:27472866:C:A	F75L	0.640

dbSNP variants (sampled 300 via entrez): RS1000041098 (12:27488704 A>G,T), RS1000107868 (12:27490014 A>G), RS1000111667 (12:27438855 G>A), RS1000113439 (12:27482507 G>A), RS1000119445 (12:27421679 T>G), RS1000142942 (12:27487722 A>G,T), RS1000184224 (12:27465457 G>C), RS1000186291 (12:27441252 C>G), RS1000210500 (12:27481489 A>C), RS1000221506 (12:27475571 T>C), RS1000251782 (12:27493154 G>A), RS1000255963 (12:27422022 A>G), RS1000288947 (12:27432683 C>T), RS1000352848 (12:27500396 A>C), RS1000356973 (12:27475841 C>A,G,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003674_5	Obstructive sleep apnea trait (apnea hypopnea index)	5.000000e-07
GCST004749_34	Lung cancer in ever smokers	5.000000e-06
GCST010002_212	Refractive error	2.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007817	sleep apnea measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	decreases expression	1
Estradiol	decreases expression	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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