C5orf46

Summary

C5orf46 (chromosome 5 open reading frame 46, HGNC:33768) is a protein-coding gene on chromosome 5q32, encoding Uncharacterized protein C5orf46 (Q6UWT4).

Located in extracellular exosome.

Source: NCBI Gene 389336 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 9 total — 3 pathogenic
• MANE Select transcript: NM_206966

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33768
Approved symbol	C5orf46
Name	chromosome 5 open reading frame 46
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	MGC23985, SSSP1, AP-64
Ensembl gene	ENSG00000178776
Ensembl biotype	protein_coding
Entrez	389336

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000318315, ENST00000510432, ENST00000515291, ENST00000955897, ENST00000955898

RefSeq mRNA: 1 — MANE Select: NM_206966 NM_206966

CCDS: CCDS34267

Canonical transcript exons

ENST00000318315 — 4 exons

Exon	Start	End
ENSE00001238658	147906432	147906538
ENSE00001416461	147892722	147892939
ENSE00001417308	147896984	147897041
ENSE00003620716	147901629	147901773

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 98.74.

FANTOM5 (CAGE): breadth broad, TPM avg 6.5005 / max 570.7692, expressed in 446 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64084	6.5005	446

Top tissues by expression

238 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	98.74	gold quality
upper leg skin	UBERON:0004262	97.63	gold quality
penis	UBERON:0000989	96.99	gold quality
skin of leg	UBERON:0001511	96.05	gold quality
zone of skin	UBERON:0000014	95.77	gold quality
skin of abdomen	UBERON:0001416	95.66	gold quality
ascending aorta	UBERON:0001496	95.62	gold quality
thoracic aorta	UBERON:0001515	95.17	gold quality
skin of hip	UBERON:0001554	93.30	gold quality
mammalian vulva	UBERON:0000997	92.69	gold quality
parotid gland	UBERON:0001831	91.94	gold quality
nipple	UBERON:0002030	89.37	gold quality
descending thoracic aorta	UBERON:0002345	86.80	gold quality
right coronary artery	UBERON:0001625	86.02	gold quality
aorta	UBERON:0000947	85.06	gold quality
saliva-secreting gland	UBERON:0001044	84.22	gold quality
apex of heart	UBERON:0002098	83.95	gold quality
left testis	UBERON:0004533	82.73	gold quality
right testis	UBERON:0004534	82.35	gold quality
saphenous vein	UBERON:0007318	81.35	gold quality
minor salivary gland	UBERON:0001830	81.21	gold quality
left coronary artery	UBERON:0001626	79.73	gold quality
testis	UBERON:0000473	79.54	gold quality
coronary artery	UBERON:0001621	79.27	gold quality
heart left ventricle	UBERON:0002084	78.69	gold quality
cardiac ventricle	UBERON:0002082	78.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.98	gold quality
popliteal artery	UBERON:0002250	77.58	gold quality
mouth mucosa	UBERON:0003729	77.54	gold quality
tibial artery	UBERON:0007610	77.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting C5orf46, 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-4455	100.00	65.48	1587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-609	99.82	64.26	505
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-7843-3P	98.31	67.94	803
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-7154-3P	97.65	65.02	985
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-505-5P	97.01	65.54	778
HSA-MIR-1226-5P	96.50	65.28	643

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gm94	ENSMUSG00000071858
rattus_norvegicus	C18h5orf46	ENSRNOG00000039260

Protein

Protein identifiers

Uncharacterized protein C5orf46 — Q6UWT4 (reviewed: Q6UWT4)

All UniProt accessions (1): Q6UWT4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UWT4-1	1	yes
Q6UWT4-2	2

RefSeq proteins (1): NP_996849* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027950	DUF4576	Family

Pfam: PF15144

UniProt features (6 total): signal peptide 1, chain 1, region of interest 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWT4-F1	64.94	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 36 (showing top): SENESE_HDAC1_AND_HDAC2_TARGETS_DN, FREAC3_01, TGACATY_UNKNOWN, CREB_Q2_01, chr5q32, MYC_UP.V1_UP, GATA1_05, LHX9_TARGET_GENES, MIR548E_5P, MIR6124, GSE10240_IL22_VS_IL22_AND_IL17_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_DN, GSE10240_IL17_VS_IL17_AND_IL22_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_DN, MIR505_5P, GSE13485_CTRL_VS_DAY21_YF17D_VACCINE_PBMC_DN, GSE13485_DAY3_VS_DAY21_YF17D_VACCINE_PBMC_DN

GO Biological Process (0):

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

GO Cellular Component (2): extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

272 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C5orf46	WFDC5	Q8TCV5	479
C5orf46	MUCL1	Q96DR8	445
C5orf46	ADGRF4	Q8IZF3	433
C5orf46	GPR87	Q9BY21	420
C5orf46	SUMO4	Q6EEV6	420
C5orf46	CDHR1	Q96JP9	419
C5orf46	LYNX1	P0DP58	397
C5orf46	SUMO2	P55855	389
C5orf46	SERPINB7	O75635	380
C5orf46	TMEM45A	Q9NWC5	362
C5orf46	WFDC12	Q8WWY7	358
C5orf46	MYOCOS	A0A1B0GUC4	349
C5orf46	C9J5N1	C9J5N1	323
C5orf46	MAGEB6	Q8N7X4	323
C5orf46	AARSD1	Q9BTE6	320

IntAct

41 interactions, top by confidence:

A	B	Type	Score
C5orf46	TMBIM6	psi-mi:“MI:0914”(association)	0.560
C5orf46	TBXA2R	psi-mi:“MI:0915”(physical association)	0.560
C5orf46	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
SGTA	C5orf46	psi-mi:“MI:0915”(physical association)	0.560
C5orf46	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
C5orf46	SGTB	psi-mi:“MI:0915”(physical association)	0.560
AQP6	C5orf46	psi-mi:“MI:0915”(physical association)	0.560
TBXA2R	C5orf46	psi-mi:“MI:0915”(physical association)	0.560
PEX12	C5orf46	psi-mi:“MI:0915”(physical association)	0.560
C5orf46	TMEM80	psi-mi:“MI:0915”(physical association)	0.560
C5orf46	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
C5orf46	RUSF1	psi-mi:“MI:0915”(physical association)	0.560
C5orf46	FAM210B	psi-mi:“MI:0915”(physical association)	0.560
EBP	C5orf46	psi-mi:“MI:0915”(physical association)	0.560
C5orf46	TMBIM6	psi-mi:“MI:0915”(physical association)	0.560
C5orf46	SGTA	psi-mi:“MI:0915”(physical association)	0.000
C5orf46	SLC30A2	psi-mi:“MI:0915”(physical association)	0.000
C5orf46	SGTB	psi-mi:“MI:0915”(physical association)	0.000
C5orf46	PEX12	psi-mi:“MI:0915”(physical association)	0.000
C5orf46	TMEM80	psi-mi:“MI:0915”(physical association)	0.000
C5orf46	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.000
C5orf46	RUSF1	psi-mi:“MI:0915”(physical association)	0.000
C5orf46	FAM210B	psi-mi:“MI:0915”(physical association)	0.000
C5orf46	AQP6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): PPCS (Affinity Capture-MS), TMBIM6 (Affinity Capture-MS), C5orf46 (Two-hybrid), C5orf46 (Two-hybrid), C5orf46 (Two-hybrid), C5orf46 (Two-hybrid), C5orf46 (Two-hybrid), C5orf46 (Two-hybrid), C5orf46 (Two-hybrid), C5orf46 (Two-hybrid), C5orf46 (Two-hybrid), C5orf46 (Two-hybrid), LHFPL5 (Two-hybrid), SGTB (Two-hybrid), C5orf46 (Positive Genetic)

ESM2 similar proteins: A0A1S4FQ37, A0A6B9L4T1, A2XAM1, A3KQQ9, A3RGB1, A6QLI2, D1FQ14, F5HF90, F7E728, H2A0M1, H7C7P1, O01949, O94356, P04923, P04926, P08725, P13828, P16845, P32778, P36046, P47868, P53278, P86958, Q02448, Q04807, Q19970, Q3T146, Q3V2D2, Q45206, Q45214, Q45215, Q54IN6, Q5MIT9, Q6R7H2, Q6UWT4, Q7YT37, Q8SRT0, Q8SV33, Q8SWP0, Q8T117

Diamond homologs: Q3T146, Q3V2D2, Q6UWT4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	2
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
147500	GRCh38/hg38 5q32(chr5:145197355-148541511)x1	Pathogenic
2685176	GRCh37/hg19 5q32(chr5:147165102-147600692)x1	Pathogenic
3246298	NC_000005.9:g.(?147204224)(147516554_?)del	Pathogenic

SpliceAI

606 predictions. Top by Δscore:

Variant	Effect	Δscore
5:147881444:A:AG	acceptor_gain	1.0000
5:147881445:G:GA	acceptor_gain	1.0000
5:147881445:GCT:G	acceptor_gain	1.0000
5:147881445:GCTA:G	acceptor_gain	1.0000
5:147881594:G:GT	donor_gain	1.0000
5:147901623:GCTTA:G	donor_loss	1.0000
5:147901624:CTT:C	donor_loss	1.0000
5:147901625:TTAC:T	donor_loss	1.0000
5:147901626:TA:T	donor_loss	1.0000
5:147901627:A:AC	donor_gain	1.0000
5:147901627:ACG:A	donor_loss	1.0000
5:147901628:C:CC	donor_gain	1.0000
5:147901628:CGTG:C	donor_gain	1.0000
5:147901771:CGT:C	acceptor_gain	1.0000
5:147901773:TC:T	acceptor_loss	1.0000
5:147901774:C:CA	acceptor_loss	1.0000
5:147901775:T:G	acceptor_loss	1.0000
5:147881442:GCA:G	acceptor_loss	0.9900
5:147881443:CAG:C	acceptor_loss	0.9900
5:147881445:GC:G	acceptor_gain	0.9900
5:147881445:GCTAC:G	acceptor_gain	0.9900
5:147881586:GGGC:G	donor_gain	0.9900
5:147881683:G:T	donor_gain	0.9900
5:147892939:CCTT:C	acceptor_gain	0.9900
5:147892942:T:C	acceptor_gain	0.9900
5:147892942:T:TC	acceptor_gain	0.9900
5:147892955:C:CT	acceptor_gain	0.9900
5:147901627:ACGTG:A	donor_gain	0.9900
5:147901628:CGTGC:C	donor_gain	0.9900
5:147901631:G:A	donor_gain	0.9900

AlphaMissense

567 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:147901666:C:G	A60P	0.974
5:147906465:C:G	G13R	0.974
5:147906465:C:T	G13R	0.974
5:147901687:C:G	G53R	0.972
5:147901686:C:T	G53D	0.970
5:147901700:G:C	F48L	0.968
5:147901700:G:T	F48L	0.968
5:147901702:A:G	F48L	0.968
5:147901677:A:G	I56T	0.955
5:147901677:A:C	I56S	0.954
5:147901687:C:A	G53C	0.950
5:147906464:C:T	G13E	0.946
5:147901698:A:T	L49Q	0.944
5:147901665:G:T	A60E	0.943
5:147901674:A:T	I57N	0.941
5:147901686:C:A	G53V	0.941
5:147901701:A:C	F48C	0.931
5:147901662:A:T	V61D	0.930
5:147901698:A:G	L49P	0.929
5:147901698:A:C	L49R	0.925
5:147901701:A:G	F48S	0.917
5:147901677:A:T	I56N	0.904
5:147901707:G:A	P46L	0.900
5:147901650:A:G	L65P	0.891
5:147901655:G:C	F63L	0.890
5:147901655:G:T	F63L	0.890
5:147901657:A:G	F63L	0.890
5:147901656:A:G	F63S	0.888
5:147901653:A:T	I64N	0.887
5:147901707:G:T	P46H	0.877

dbSNP variants (sampled 300 via entrez): RS1000062454 (5:147905047 T>C), RS1000318734 (5:147893023 C>A,T), RS1000434750 (5:147905217 G>A), RS1000510319 (5:147903975 T>C), RS1000541279 (5:147908535 C>A,T), RS1000711172 (5:147885680 CCA>C), RS1001058324 (5:147893427 G>A,C), RS1001080979 (5:147887243 C>G), RS1001143439 (5:147886955 G>A), RS1001201244 (5:147887613 C>T), RS1001359205 (5:147899653 C>T), RS1001416565 (5:147889447 T>C), RS1001639119 (5:147905912 A>G), RS1001813936 (5:147907304 T>C), RS1001831346 (5:147893547 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): ichthyosis linearis circumflexa (MONDO:0043106)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004860_95	Alcoholic chronic pancreatitis	3.000000e-15

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	increases expression	1
clothianidin	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Oxygen	increases expression	1
Dronabinol	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Cyclosporine	decreases expression	1
Sodium Selenite	decreases expression	1
Lactic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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