SMCO3

Summary

SMCO3 (single-pass membrane protein with coiled-coil domains 3, HGNC:34401) is a protein-coding gene on chromosome 12p12.3, encoding Single-pass membrane and coiled-coil domain-containing protein 3 (A2RU48).

Predicted to be located in membrane.

Source: NCBI Gene 440087 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001013698

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34401
Approved symbol	SMCO3
Name	single-pass membrane protein with coiled-coil domains 3
Location	12p12.3
Locus type	gene with protein product
Status	Approved
Aliases	LOC440087
Ensembl gene	ENSG00000179256
Ensembl biotype	protein_coding
Entrez	440087

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000316048, ENST00000858169

RefSeq mRNA: 1 — MANE Select: NM_001013698 NM_001013698

CCDS: CCDS41759

Canonical transcript exons

ENST00000316048 — 2 exons

Exon	Start	End
ENSE00001216253	14804650	14806696
ENSE00001535582	14814126	14814182

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 83.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3042 / max 31.3534, expressed in 98 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129855	0.3042	98

Top tissues by expression

230 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	83.49	gold quality
tibial nerve	UBERON:0001323	72.30	gold quality
kidney epithelium	UBERON:0004819	70.67	gold quality
decidua	UBERON:0002450	68.54	gold quality
amniotic fluid	UBERON:0000173	66.21	silver quality
gall bladder	UBERON:0002110	65.54	gold quality
right coronary artery	UBERON:0001625	65.50	gold quality
right lung	UBERON:0002167	64.05	gold quality
left coronary artery	UBERON:0001626	63.82	gold quality
tibial artery	UBERON:0007610	63.66	gold quality
popliteal artery	UBERON:0002250	63.63	gold quality
coronary artery	UBERON:0001621	63.00	gold quality
tibialis anterior	UBERON:0001385	62.64	silver quality
adult mammalian kidney	UBERON:0000082	62.01	gold quality
calcaneal tendon	UBERON:0003701	61.98	gold quality
pancreatic ductal cell	CL:0002079	61.27	silver quality
aorta	UBERON:0000947	61.04	gold quality
ileal mucosa	UBERON:0000331	59.95	silver quality
metanephros cortex	UBERON:0010533	59.13	gold quality
right atrium auricular region	UBERON:0006631	58.18	gold quality
deltoid	UBERON:0001476	58.13	silver quality
ascending aorta	UBERON:0001496	58.13	gold quality
thoracic aorta	UBERON:0001515	57.88	gold quality
endocervix	UBERON:0000458	57.79	gold quality
cardiac atrium	UBERON:0002081	57.71	gold quality
kidney	UBERON:0002113	57.50	gold quality
epithelial cell of pancreas	CL:0000083	57.29	gold quality
cortex of kidney	UBERON:0001225	57.13	gold quality
sperm	CL:0000019	55.78	gold quality
trigeminal ganglion	UBERON:0001675	55.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

76 targeting SMCO3, 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-3646	100.00	73.56	5283
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-105-5P	99.54	69.24	2060

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Smco3	ENSMUSG00000043298
rattus_norvegicus	Smco3l1	ENSRNOG00000066655
rattus_norvegicus	Smco3	ENSRNOG00000066886

Protein

Protein identifiers

Single-pass membrane and coiled-coil domain-containing protein 3 — A2RU48 (reviewed: A2RU48)

All UniProt accessions (1): A2RU48

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001013720* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027895	DUF4533	Family
IPR040004	SMCO3	Family

Pfam: PF15047

UniProt features (6 total): coiled-coil region 2, sequence variant 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A2RU48-F1	81.62	0.32

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, chr12p12, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, MIR3646, MIR3658, MIR450B_5P, MIR4311, MIR1208, MIR2681_5P, MIR19A_5P, MIR19B_1_5P_MIR19B_2_5P, MIR6740_3P, MIR190B_3P, MIR6079, MIR6748_3P

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

134 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMCO3	OR1J4	Q8NGS1	644
SMCO3	C12orf60	Q5U649	609
SMCO3	SATL1	Q86VE3	608
SMCO3	CBLL2	Q8N7E2	571
SMCO3	MROH6	A6NGR9	562
SMCO3	VN1R1	Q9GZP7	542
SMCO3	SPRYD4	Q8WW59	539
SMCO3	JAKMIP3	Q5VZ66	489
SMCO3	NPIPA3	F8WFD2	469
SMCO3	OOEP	A6NGQ2	450
SMCO3	ERP27	Q96DN0	417
SMCO3	SPPL2B	Q8TCT7	404
SMCO3	ANKRD46	Q86W74	378
SMCO3	CLASRP	Q8N2M8	375
SMCO3	SH3TC2	Q8TF17	354

IntAct

19 interactions, top by confidence:

A	B	Type	Score
SMCO3	MAPK9	psi-mi:“MI:0915”(physical association)	0.720
MAPK9	SMCO3	psi-mi:“MI:0915”(physical association)	0.720
TRIM39	SMCO3	psi-mi:“MI:0915”(physical association)	0.560
SMCO3	PSMA6	psi-mi:“MI:0915”(physical association)	0.560
STN1	SMCO3	psi-mi:“MI:0914”(association)	0.530
PPP2CA	SMCO3	psi-mi:“MI:0914”(association)	0.420
PPP2CA	SMCO3	psi-mi:“MI:2364”(proximity)	0.420
SMCO3	FUS	psi-mi:“MI:0915”(physical association)	0.400
P		psi-mi:“MI:0914”(association)	0.350
PSMA6	SMCO3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): SMCO3 (Two-hybrid), SMCO3 (Two-hybrid), SMCO3 (Affinity Capture-MS), SMCO3 (Affinity Capture-MS), FUS (Affinity Capture-MS), SMCO3 (Affinity Capture-MS), SMCO3 (Proximity Label-MS), SMCO3 (Two-hybrid), SMCO3 (Two-hybrid), SMCO3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0H2XDF9, A0A0H2XIE9, A2RU48, B3STP6, B7XHM5, C7GUN6, G2TRQ4, O05453, O06966, O31557, O31558, O32000, O33084, O84673, P0C047, P0DOB0, P39609, P42295, P64668, P65088, P77335, P80172, P96721, P9WI00, P9WI01, P9WJD0, P9WJD1, P9WJD6, P9WJD7, P9WM98, P9WM99, P9WNI2, P9WNI3, P9WNJ8, P9WNJ9, Q2G182, Q47502, Q49723, Q49945, Q5HJ84

Diamond homologs: A2RU48, Q8BQM7

SIGNOR signaling

0 interactions.

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	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

486 predictions. Top by Δscore:

Variant	Effect	Δscore
12:14806694:TCG:T	acceptor_gain	0.9900
12:14806695:CG:C	acceptor_gain	0.9900
12:14806695:CGC:C	acceptor_gain	0.9900
12:14806697:C:CC	acceptor_gain	0.9900
12:14814121:CTTA:C	donor_loss	0.9900
12:14814122:TTAC:T	donor_loss	0.9900
12:14814123:TACCT:T	donor_loss	0.9900
12:14814125:CCTTG:C	donor_gain	0.9900
12:14806692:GATCG:G	acceptor_gain	0.9800
12:14813553:A:AC	donor_gain	0.9800
12:14813554:C:CC	donor_gain	0.9800
12:14814124:A:AC	donor_gain	0.9800
12:14814125:C:CC	donor_gain	0.9800
12:14806693:ATCGC:A	acceptor_loss	0.9700
12:14806695:CGCTG:C	acceptor_loss	0.9700
12:14806696:GCTG:G	acceptor_loss	0.9700
12:14806697:CTG:C	acceptor_loss	0.9700
12:14806698:T:A	acceptor_loss	0.9700
12:14806693:ATCG:A	acceptor_gain	0.9600
12:14809238:T:TA	donor_gain	0.9600
12:14806699:GAAAA:G	acceptor_loss	0.9500
12:14806700:AAAAA:A	acceptor_loss	0.9500
12:14806064:G:GC	acceptor_gain	0.9400
12:14813503:G:T	donor_gain	0.9400
12:14814124:AC:A	donor_gain	0.9400
12:14814125:CC:C	donor_gain	0.9400
12:14813201:TG:T	donor_gain	0.9300
12:14814125:CCTT:C	donor_gain	0.9300
12:14806062:CTG:C	acceptor_gain	0.9200
12:14813549:G:A	donor_gain	0.9100

AlphaMissense

1482 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:14806607:A:G	L25P	0.979
12:14806565:A:G	L39P	0.968
12:14806076:A:G	F202S	0.967
12:14806582:G:C	F33L	0.964
12:14806582:G:T	F33L	0.964
12:14806584:A:G	F33L	0.964
12:14806085:A:G	L199P	0.962
12:14806421:A:G	L87P	0.962
12:14806385:A:G	L99P	0.960
12:14806118:A:G	L188P	0.959
12:14806553:A:G	L43P	0.959
12:14806075:G:C	F202L	0.958
12:14806075:G:T	F202L	0.958
12:14806077:A:G	F202L	0.958
12:14806110:C:G	A191P	0.958
12:14806294:A:C	S129R	0.954
12:14806294:A:T	S129R	0.954
12:14806296:T:G	S129R	0.954
12:14806619:A:G	L21P	0.954
12:14806409:A:G	L91P	0.950
12:14806486:G:C	N65K	0.949
12:14806486:G:T	N65K	0.949
12:14806286:G:T	A132D	0.947
12:14806056:A:C	Y209D	0.946
12:14806585:G:C	S32R	0.944
12:14806585:G:T	S32R	0.944
12:14806587:T:G	S32R	0.944
12:14806047:C:G	A212P	0.941
12:14806289:A:T	V131D	0.928
12:14806055:T:G	Y209S	0.927

dbSNP variants (sampled 300 via entrez): RS1000222940 (12:14809439 G>T), RS1000254290 (12:14809151 A>G), RS1000402866 (12:14810367 G>A), RS1000732948 (12:14808884 T>C), RS1001106808 (12:14814303 C>T), RS1001180256 (12:14808209 T>A,C), RS1002218353 (12:14806328 G>A), RS1002297918 (12:14807074 C>T), RS1002490022 (12:14812109 A>G), RS1002510138 (12:14812669 G>A,C), RS1002521265 (12:14812300 C>T), RS1002613263 (12:14813230 C>T), RS1003046641 (12:14805599 C>G), RS1003486033 (12:14811795 C>T), RS1004166247 (12:14810443 C>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

1 associations (top):

Study	Trait	p-value
GCST90000025_1024	Appendicular lean mass	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, decreases methylation	2
abrine	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
incobotulinumtoxinA	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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