SYS1

Summary

SYS1 (SYS1 golgi trafficking protein, HGNC:16162) is a protein-coding gene on chromosome 20q13.12, encoding Protein SYS1 homolog (Q8N2H4). Involved in protein trafficking. It is a common-essential gene (DepMap: required in 94.5% of cancer cell lines).

SYS1 forms a complex with ADP-ribosylation factor-related protein ARFRP1 (MIM 604699) and targets ARFRP1 to the Golgi apparatus (Behnia et al., 2004 [PubMed 15077113]).

Source: NCBI Gene 90196 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 61 total
• Cancer dependency (DepMap): dependent in 94.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_033542

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16162
Approved symbol	SYS1
Name	SYS1 golgi trafficking protein
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	dJ453C12.4
Ensembl gene	ENSG00000204070
Ensembl biotype	protein_coding
OMIM	612979
Entrez	90196

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000243918, ENST00000372727, ENST00000414310, ENST00000426004, ENST00000453003, ENST00000457307, ENST00000461890, ENST00000479779, ENST00000892152, ENST00000892153, ENST00000892154, ENST00000966582, ENST00000966583, ENST00000966584

RefSeq mRNA: 3 — MANE Select: NM_033542 NM_001099791, NM_001197129, NM_033542

CCDS: CCDS13351, CCDS56192

Canonical transcript exons

ENST00000243918 — 4 exons

Exon	Start	End
ENSE00001125580	45363156	45363315
ENSE00001458470	45366875	45369209
ENSE00003621956	45365619	45365686
ENSE00003635135	45363529	45363693

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 88.97.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5175 / max 15.4556, expressed in 231 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184885	35.0000	1824
184887	3.7236	1313
184884	0.2222	94
184886	0.1734	67
184888	0.1219	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	88.97	gold quality
granulocyte	CL:0000094	88.85	gold quality
tibialis anterior	UBERON:0001385	88.76	silver quality
ileal mucosa	UBERON:0000331	88.72	gold quality
lymph node	UBERON:0000029	88.46	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.97	gold quality
gall bladder	UBERON:0002110	87.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.70	gold quality
kidney epithelium	UBERON:0004819	87.59	silver quality
smooth muscle tissue	UBERON:0001135	87.58	gold quality
blood	UBERON:0000178	87.46	gold quality
gastrocnemius	UBERON:0001388	87.35	gold quality
muscle of leg	UBERON:0001383	87.23	gold quality
right adrenal gland	UBERON:0001233	87.14	gold quality
body of stomach	UBERON:0001161	86.97	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.97	gold quality
upper lobe of left lung	UBERON:0008952	86.89	gold quality
adult mammalian kidney	UBERON:0000082	86.80	gold quality
endocervix	UBERON:0000458	86.80	gold quality
body of uterus	UBERON:0009853	86.77	gold quality
left ovary	UBERON:0002119	86.75	gold quality
fallopian tube	UBERON:0003889	86.74	gold quality
right adrenal gland cortex	UBERON:0035827	86.74	gold quality
left adrenal gland	UBERON:0001234	86.72	gold quality
right ovary	UBERON:0002118	86.67	gold quality
left uterine tube	UBERON:0001303	86.52	gold quality
leukocyte	CL:0000738	86.46	gold quality
cortical plate	UBERON:0005343	86.46	gold quality
pancreas	UBERON:0001264	86.44	gold quality
upper lobe of lung	UBERON:0008948	86.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting SYS1, 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-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-609	99.82	64.26	505
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-12132	99.47	68.90	1341

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 94.5% of screened cell lines, common-essential.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sys1	ENSDARG00000017606
mus_musculus	Sys1	ENSMUSG00000045503
rattus_norvegicus	Sys1	ENSRNOG00000014480
drosophila_melanogaster	Sys1	FBGN0037603
caenorhabditis_elegans	T03F1.12	WBGENE00020193

Paralogs (1): TMEM244 (ENSG00000203756)

Protein

Protein identifiers

Protein SYS1 homolog — Q8N2H4 (reviewed: Q8N2H4)

All UniProt accessions (4): E7ETM6, F8WB21, Q5QPU8, Q8N2H4

UniProt curated annotations — full annotation on UniProt →

Function. Involved in protein trafficking. May serve as a receptor for ARFRP1.

Subunit / interactions. Interacts with ARFRP1.

Subcellular location. Golgi apparatus membrane.

Similarity. Belongs to the SYS1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N2H4-1	1	yes
Q8N2H4-2	2

RefSeq proteins (3): NP_001093261, NP_001184058, NP_291020* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016973	Integral_membrane_SYS1	Family
IPR019185	Integral_membrane_SYS1-rel	Family

Pfam: PF09801

UniProt features (6 total): transmembrane region 4, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N2H4-F1	91.69	0.81

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic

MSigDB gene sets: 156 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, CHANDRAN_METASTASIS_DN, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_GOLGI_TO_PLASMA_MEMBRANE_TRANSPORT, GOCC_TRANS_GOLGI_NETWORK, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_GOLGI_TO_ENDOSOME_TRANSPORT, GOBP_GOLGI_TO_PLASMA_MEMBRANE_PROTEIN_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_GOLGI_APPARATUS, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_PLASMA_MEMBRANE

GO Biological Process (4): Golgi to endosome transport (GO:0006895), protein localization to Golgi apparatus (GO:0034067), Golgi to plasma membrane protein transport (GO:0043001), protein transport (GO:0015031)

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

GO Cellular Component (6): Golgi membrane (GO:0000139), trans-Golgi network (GO:0005802), cytosol (GO:0005829), trans-Golgi network membrane (GO:0032588), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
post-Golgi vesicle-mediated transport	1
intercellular transport	1
cytosolic transport	1
protein localization to organelle	1
Golgi to plasma membrane transport	1
protein transport	1
establishment of protein localization to plasma membrane	1
protein localization to plasma membrane	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
Golgi apparatus subcompartment	1
trans-Golgi network	1
organelle membrane	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

752 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYS1	ARFRP1	Q13795	962
SYS1	ARL3	P36405	867
SYS1	NAA38	Q9BRA0	621
SYS1	DBNDD2	Q9BQY9	580
SYS1	TP53TG5	Q9Y2B4	511
SYS1	A0A1B0GW23	A0A1B0GW23	506
SYS1	COG3	Q96JB2	500
SYS1	SEC24B	O95487	492
SYS1	RIC1	Q4ADV7	481
SYS1	NAA30	Q147X3	480
SYS1	VPS11	Q9H270	480
SYS1	SMIM15	Q7Z3B0	475
SYS1	PMP2	P02689	465
SYS1	SPATA25	Q9BR10	461
SYS1	ARL5A	Q9Y689	453

IntAct

59 interactions, top by confidence:

A	B	Type	Score
TNFSF14	SYS1	psi-mi:“MI:0915”(physical association)	0.560
IL3RA	SYS1	psi-mi:“MI:0915”(physical association)	0.560
PVR	SYS1	psi-mi:“MI:0915”(physical association)	0.560
SYS1	SLC35C2	psi-mi:“MI:0915”(physical association)	0.560
SYS1	TMEM248	psi-mi:“MI:0915”(physical association)	0.560
SYS1	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
MGST3	SYS1	psi-mi:“MI:0915”(physical association)	0.560
SYS1	MCFD2	psi-mi:“MI:0915”(physical association)	0.560
EBP	SYS1	psi-mi:“MI:0915”(physical association)	0.560
SYS1	MRPS18B	psi-mi:“MI:0915”(physical association)	0.560
SYS1	TM4SF19	psi-mi:“MI:0915”(physical association)	0.560
SYS1	HSD17B11	psi-mi:“MI:0915”(physical association)	0.560
SYS1	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
BTNL9	SYS1	psi-mi:“MI:0915”(physical association)	0.560
SLC30A8	SYS1	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	SYS1	psi-mi:“MI:0915”(physical association)	0.560
	SYS1	psi-mi:“MI:0915”(physical association)	0.560
SYS1	KIR3DL3	psi-mi:“MI:0915”(physical association)	0.560
SYS1	COX6B1	psi-mi:“MI:0914”(association)	0.350
SYS1	TNFSF14	psi-mi:“MI:0915”(physical association)	0.000
SYS1	TMEM248	psi-mi:“MI:0915”(physical association)	0.000
SYS1	ELOVL5	psi-mi:“MI:0915”(physical association)	0.000
SYS1	MGST3	psi-mi:“MI:0915”(physical association)	0.000
SYS1	MCFD2	psi-mi:“MI:0915”(physical association)	0.000
SYS1	EBP	psi-mi:“MI:0915”(physical association)	0.000
SYS1	MRPS18B	psi-mi:“MI:0915”(physical association)	0.000
SYS1	TM4SF19	psi-mi:“MI:0915”(physical association)	0.000
SYS1	HSD17B11	psi-mi:“MI:0915”(physical association)	0.000
SYS1	ERGIC3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): SYS1 (PCA), SYS1 (Two-hybrid), SYS1 (Two-hybrid), SYS1 (Two-hybrid), SYS1 (Two-hybrid), SYS1 (Two-hybrid), SYS1 (Two-hybrid), SYS1 (Two-hybrid), SYS1 (Two-hybrid), SYS1 (Two-hybrid), SYS1 (Two-hybrid), SYS1 (Two-hybrid), SYS1 (Two-hybrid), SYS1 (Two-hybrid), SYS1 (Two-hybrid)

ESM2 similar proteins: A2AF53, A4FV75, A4K2N5, A4K2W1, A5A6S6, A6QL84, A6ZIQ8, A9JRA0, B1AZA5, D3ZEH5, D3ZXD8, E1BD52, O60337, P58749, Q08DE2, Q108U3, Q2TBU2, Q3SYY9, Q3TMP8, Q4R5E3, Q58DA4, Q5BJW3, Q5JZQ8, Q5R8H8, Q5R9W1, Q5RBJ7, Q5RFE0, Q5ZII3, Q62302, Q6UWH6, Q6ZQ89, Q78S06, Q7SYC7, Q7ZUA6, Q86W33, Q8CIF6, Q8K0B2, Q8N2H4, Q8NBJ9, Q8NFB2

Diamond homologs: A4K2N5, A4K2W1, A7S6Y0, Q1RMQ3, Q55E69, Q78S06, Q8N2H4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

926 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45362024:GAA:G	donor_gain	1.0000
20:45362026:A:AG	donor_gain	1.0000
20:45362030:G:GG	donor_gain	1.0000
20:45363524:TGCA:T	acceptor_loss	1.0000
20:45363525:GCAG:G	acceptor_loss	1.0000
20:45363526:CAGG:C	acceptor_loss	1.0000
20:45363527:AG:A	acceptor_gain	1.0000
20:45363528:G:A	acceptor_loss	1.0000
20:45363528:GG:G	acceptor_gain	1.0000
20:45363528:GGGC:G	acceptor_gain	1.0000
20:45363691:GAG:G	donor_gain	1.0000
20:45363692:AGGT:A	donor_loss	1.0000
20:45363694:G:GG	donor_gain	1.0000
20:45363694:GTA:G	donor_loss	1.0000
20:45363695:T:A	donor_loss	1.0000
20:45366873:A:AG	acceptor_gain	1.0000
20:45366874:G:GG	acceptor_gain	1.0000
20:45362025:AATAA:A	donor_gain	0.9900
20:45362026:A:G	donor_gain	0.9900
20:45362027:TAA:T	donor_gain	0.9900
20:45362028:AAG:A	donor_loss	0.9900
20:45362030:GT:G	donor_loss	0.9900
20:45362035:T:G	donor_gain	0.9900
20:45363313:CTG:C	donor_gain	0.9900
20:45363316:G:GA	donor_loss	0.9900
20:45363527:A:AG	acceptor_gain	0.9900
20:45363527:AGG:A	acceptor_gain	0.9900
20:45363528:G:GA	acceptor_gain	0.9900
20:45363528:GGG:G	acceptor_gain	0.9900
20:45363528:GGGCA:G	acceptor_gain	0.9900

AlphaMissense

996 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45366924:T:C	F94L	0.999
20:45366926:C:A	F94L	0.999
20:45366926:C:G	F94L	0.999
20:45367081:T:C	I146T	0.998
20:45363544:T:C	F5L	0.997
20:45363546:C:A	F5L	0.997
20:45363546:C:G	F5L	0.997
20:45366917:T:G	C91W	0.997
20:45366923:T:A	D93E	0.997
20:45366923:T:G	D93E	0.997
20:45367002:T:A	W120R	0.997
20:45367002:T:C	W120R	0.997
20:45367044:G:A	G134R	0.997
20:45367044:G:C	G134R	0.997
20:45367044:G:T	G134W	0.997
20:45367045:G:A	G134E	0.997
20:45366915:T:C	C91R	0.996
20:45366922:A:T	D93V	0.996
20:45366934:C:T	T97I	0.996
20:45365675:C:A	N73K	0.995
20:45365675:C:G	N73K	0.995
20:45366882:G:C	G80R	0.995
20:45366916:G:A	C91Y	0.995
20:45366921:G:A	D93N	0.995
20:45367058:C:G	C138W	0.995
20:45367072:T:C	L143P	0.995
20:45363628:T:A	W33R	0.994
20:45363628:T:C	W33R	0.994
20:45366921:G:C	D93H	0.994
20:45366922:A:C	D93A	0.994

dbSNP variants (sampled 300 via entrez): RS1000069498 (20:45364925 A>T), RS1000252888 (20:45372757 T>C), RS1000369573 (20:45372279 C>G), RS1000533386 (20:45370770 G>A), RS1000574315 (20:45360675 T>C), RS1000603368 (20:45372500 G>A), RS1001245774 (20:45365411 T>C), RS1001359015 (20:45360353 T>C), RS1001763464 (20:45373082 C>T), RS1001857817 (20:45364541 G>A,C), RS1001889949 (20:45360697 C>T), RS1001931075 (20:45365890 A>G), RS1002351153 (20:45372353 A>C), RS1002372418 (20:45372975 A>T), RS1002424761 (20:45372689 A>G)

Disease associations

OMIM: gene MIM:612979 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005455_6	Mean diameter of HDL particles	2.000000e-20
GCST005497_3	Large HDL particle concentration	2.000000e-07
GCST005499_6	Phospholipid levels in large HDL	6.000000e-09
GCST005502_5	Free cholesterol levels in large HDL	4.000000e-08
GCST010725_40	Malaria	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008591	free cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases methylation	3
Valproic Acid	affects expression, increases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
K 7174	increases expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1
Methotrexate	increases expression	1
Ozone	increases abundance, affects cotreatment, increases oxidation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Cadmium Chloride	decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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