SMCO4

Summary

SMCO4 (single-pass membrane protein with coiled-coil domains 4, HGNC:24810) is a protein-coding gene on chromosome 11q21, encoding Single-pass membrane and coiled-coil domain-containing protein 4 (Q9NRQ5).

Predicted to be located in membrane.

Source: NCBI Gene 56935 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 14 total
• MANE Select transcript: NM_020179

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24810
Approved symbol	SMCO4
Name	single-pass membrane protein with coiled-coil domains 4
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	FN5
Ensembl gene	ENSG00000166002
Ensembl biotype	protein_coding
OMIM	609477
Entrez	56935

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 46 protein_coding

ENST00000298966, ENST00000525141, ENST00000526869, ENST00000527149, ENST00000529714, ENST00000888171, ENST00000888172, ENST00000888173, ENST00000888174, ENST00000888175, ENST00000888176, ENST00000888177, ENST00000888178, ENST00000888179, ENST00000888180, ENST00000888181, ENST00000888182, ENST00000888183, ENST00000888184, ENST00000888185, ENST00000888186, ENST00000888187, ENST00000888188, ENST00000888189, ENST00000888190, ENST00000888191, ENST00000888192, ENST00000888193, ENST00000888194, ENST00000888195, ENST00000888196, ENST00000888197, ENST00000888198, ENST00000888199, ENST00000934129, ENST00000934130, ENST00000934131, ENST00000947544, ENST00000947545, ENST00000947546, ENST00000947547, ENST00000947548, ENST00000947549, ENST00000947550, ENST00000947551, ENST00000947552

RefSeq mRNA: 1 — MANE Select: NM_020179 NM_020179

CCDS: CCDS8292

Canonical transcript exons

ENST00000298966 — 3 exons

Exon	Start	End
ENSE00001098869	93499276	93499348
ENSE00002194411	93478472	93479269
ENSE00002196994	93543276	93543391

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8418 / max 202.2657, expressed in 1542 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121825	2.8652	1147
121827	1.8615	943
121826	1.0574	682
121828	0.5985	291
121823	0.4125	122
121821	0.0466	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.59	gold quality
secondary oocyte	CL:0000655	97.35	gold quality
monocyte	CL:0000576	97.10	gold quality
mononuclear cell	CL:0000842	97.03	gold quality
leukocyte	CL:0000738	96.78	gold quality
right lobe of liver	UBERON:0001114	96.17	gold quality
jejunal mucosa	UBERON:0000399	95.23	gold quality
oocyte	CL:0000023	94.94	gold quality
left lobe of thyroid gland	UBERON:0001120	94.93	gold quality
granulocyte	CL:0000094	94.53	gold quality
right lobe of thyroid gland	UBERON:0001119	94.50	gold quality
right adrenal gland	UBERON:0001233	94.28	gold quality
right adrenal gland cortex	UBERON:0035827	94.04	gold quality
thyroid gland	UBERON:0002046	93.98	gold quality
left adrenal gland	UBERON:0001234	93.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.84	gold quality
liver	UBERON:0002107	93.78	gold quality
left adrenal gland cortex	UBERON:0035825	93.77	gold quality
mucosa of transverse colon	UBERON:0004991	93.76	gold quality
duodenum	UBERON:0002114	93.67	gold quality
colonic mucosa	UBERON:0000317	93.46	gold quality
ileal mucosa	UBERON:0000331	93.33	gold quality
saliva-secreting gland	UBERON:0001044	93.13	gold quality
body of pancreas	UBERON:0001150	93.13	gold quality
adrenal cortex	UBERON:0001235	93.10	gold quality
right uterine tube	UBERON:0001302	92.89	gold quality
right testis	UBERON:0004534	92.76	gold quality
adrenal gland	UBERON:0002369	92.71	gold quality
left testis	UBERON:0004533	92.70	gold quality
right atrium auricular region	UBERON:0006631	92.42	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	23.34
E-MTAB-6701	yes	17.79
E-ANND-3	yes	13.00
E-CURD-88	yes	8.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting SMCO4, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-146A-3P	99.13	68.99	1881

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Smco4	ENSMUSG00000058173
rattus_norvegicus	Smco4	ENSRNOG00000011162

Protein

Protein identifiers

Single-pass membrane and coiled-coil domain-containing protein 4 — Q9NRQ5 (reviewed: Q9NRQ5)

Alternative names: Protein FN5

All UniProt accessions (3): E9PQ76, E9PSB8, Q9NRQ5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the SMCO4 family.

RefSeq proteins (1): NP_064564* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027960	DUF4519	Family

Pfam: PF15012

UniProt features (5 total): 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-Q9NRQ5-F1	73.79	0.22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 219 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, YANG_BREAST_CANCER_ESR1_LASER_DN, BOHN_PRIMARY_IMMUNODEFICIENCY_SYNDROM_DN, GTGCCTT_MIR506, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, VANTVEER_BREAST_CANCER_ESR1_DN, NUYTTEN_EZH2_TARGETS_DN, SCHUETZ_BREAST_CANCER_DUCTAL_INVASIVE_UP, SMID_BREAST_CANCER_LUMINAL_B_DN, MULLIGHAN_MLL_SIGNATURE_1_UP, chr11q21, MYB_Q6, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN, LI_INDUCED_T_TO_NATURAL_KILLER_UP, PANGAS_TUMOR_SUPPRESSION_BY_SMAD1_AND_SMAD5_UP

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

266 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMCO4	VSTM5	A8MXK1	564
SMCO4	NEO1	Q92859	519
SMCO4	ZNF195	O14628	491
SMCO4	BKGD	Q9H0W9	490
SMCO4	PDZD11	Q5EBL8	436
SMCO4	FN1	P02751	435
SMCO4	DRAXIN	Q8NBI3	427
SMCO4	NTN1	O95631	413
SMCO4	NUDT6	P53370	403
SMCO4	HEPHL1	Q6MZM0	400
SMCO4	NFASC	O94856	391
SMCO4	NTN5	Q8WTR8	380
SMCO4	DCC	P43146	364
SMCO4	ZBBX	A8MT70	359
SMCO4	GALNT5	Q7Z7M9	344

IntAct

184 interactions, top by confidence:

A	B	Type	Score
SMCO4	BNIP3L	psi-mi:“MI:0915”(physical association)	0.780
BNIP3L	SMCO4	psi-mi:“MI:0915”(physical association)	0.780
	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
KRT40	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
SYNE4	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
KASH5	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	SYNE4	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	KASH5	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	KRT40	psi-mi:“MI:0915”(physical association)	0.560
SMCO4		psi-mi:“MI:0915”(physical association)	0.560
SMCO4	PTGES	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	TMX2	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	CD79A	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	TEX29	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	FFAR2	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	FAM210B	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	SLC7A14	psi-mi:“MI:0915”(physical association)	0.560
SMCO4	M6PR	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (65): SMCO4 (Two-hybrid), KRT40 (Two-hybrid), CCDC155 (Two-hybrid), SYNE4 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-3 (Two-hybrid), BNIP3L (Two-hybrid), SMCO4 (Two-hybrid), SMCO4 (Two-hybrid), SMCO4 (Two-hybrid), SMCO4 (Two-hybrid), SMCO4 (Two-hybrid), SMCO4 (Two-hybrid), SMCO4 (Two-hybrid), SMCO4 (Two-hybrid)

ESM2 similar proteins: A0M8S0, A0M8T1, A0M8U1, A2VDK9, A3KN28, A4D7R9, A9JRA0, B5FXC9, P42553, P42554, Q00PJ0, Q07DV5, Q07DW9, Q07DX8, Q07DY8, Q07E08, Q07E45, Q09YH4, Q09YI5, Q09YJ7, Q09YK8, Q09YN2, Q0VCK9, Q108U3, Q1RLU8, Q2IBA8, Q2IBD0, Q2IBE0, Q2IBE8, Q2PG42, Q2QL86, Q2QLA6, Q2QLB7, Q2QLD7, Q2QLE8, Q2QLG2, Q32PD9, Q3ZAQ7, Q5RDV3, Q68FW3

Diamond homologs: A7RYM6, A7RYM7, B0WN94, B5FXC9, Q0IFA9, Q32PD9, Q6GP51, Q7PH91, Q8SY72, Q9I859, Q9JIS3, Q9NRQ5, Q09JL7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

401 predictions. Top by Δscore:

Variant	Effect	Δscore
11:93479267:CTC:C	acceptor_gain	0.9900
11:93479268:TCC:T	acceptor_loss	0.9900
11:93479270:C:CG	acceptor_loss	0.9900
11:93479271:T:G	acceptor_loss	0.9900
11:93499272:TTA:T	donor_loss	0.9900
11:93479270:C:CC	acceptor_gain	0.9800
11:93496323:T:TC	acceptor_gain	0.9800
11:93479268:TC:T	acceptor_gain	0.9700
11:93479269:CC:C	acceptor_gain	0.9700
11:93499274:A:AC	donor_gain	0.9700
11:93499275:C:CC	donor_gain	0.9700
11:93479265:ACCTC:A	acceptor_gain	0.9600
11:93479266:CCTCC:C	acceptor_gain	0.9600
11:93479280:AACAA:A	acceptor_gain	0.9600
11:93479282:CAA:C	acceptor_gain	0.9600
11:93496323:T:C	acceptor_gain	0.9600
11:93479272:G:C	acceptor_loss	0.9400
11:93479281:ACAA:A	acceptor_gain	0.9200
11:93479282:CAAC:C	acceptor_gain	0.9200
11:93479267:CTCCT:C	acceptor_gain	0.9100
11:93479272:G:GC	acceptor_gain	0.8700
11:93499289:T:TA	donor_gain	0.8500
11:93479266:CCTC:C	acceptor_gain	0.8400
11:93479267:CTCC:C	acceptor_gain	0.8400
11:93479268:TCCT:T	acceptor_gain	0.8400
11:93496811:T:A	donor_gain	0.8400
11:93497835:CTCT:C	acceptor_gain	0.8200
11:93479269:C:G	acceptor_gain	0.8100
11:93497834:ACTCT:A	acceptor_gain	0.7900
11:93479293:G:GC	acceptor_gain	0.7800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000036632 (11:93506786 T>C), RS1000103351 (11:93522291 A>G), RS1000145038 (11:93480173 T>C,G), RS1000192479 (11:93524377 C>T), RS1000195141 (11:93497343 G>A,C,T), RS1000210032 (11:93545226 A>G), RS1000281258 (11:93551298 T>C,G), RS1000324206 (11:93544875 T>C), RS1000361539 (11:93530364 G>C,T), RS1000382465 (11:93500005 A>G), RS1000419860 (11:93536539 T>A,C,G), RS1000448358 (11:93553488 A>G), RS1000541517 (11:93478896 C>A,T), RS1000602344 (11:93511426 AAG>A), RS1000606619 (11:93524059 A>C)

Disease associations

OMIM: gene MIM:609477 | 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
GCST005160_3	Insulin levels in response to oral glucose tolerance test (30 minutes)	9.000000e-06
GCST010988_425	Adult body size	1.000000e-08
GCST90013405_91	Liver enzyme levels (alanine transaminase)	2.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004307	glucose tolerance test
EFO:0004467	insulin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
potassium chromate(VI)	decreases expression, increases expression, affects cotreatment	2
Cisplatin	affects expression, increases expression	2
Tretinoin	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
sodium arsenate	decreases expression, increases abundance	1
periodate-oxidized adenosine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
gardiquimod	decreases reaction, increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	affects response to substance	1
Estradiol	decreases expression	1
Nickel	decreases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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