SYTL1

Summary

SYTL1 (synaptotagmin like 1, HGNC:15584) is a protein-coding gene on chromosome 1p36.11, encoding Synaptotagmin-like protein 1 (Q8IYJ3). May play a role in vesicle trafficking.

Predicted to enable neurexin family protein binding activity. Involved in exocytosis. Located in plasma membrane.

Source: NCBI Gene 84958 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 97 total
• MANE Select transcript: NM_001193308

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15584
Approved symbol	SYTL1
Name	synaptotagmin like 1
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	SLP1, JFC1, FLJ14996, exophilin-7
Ensembl gene	ENSG00000142765
Ensembl biotype	protein_coding
OMIM	608042
Entrez	84958

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 16 protein_coding, 6 retained_intron

ENST00000318074, ENST00000473280, ENST00000475199, ENST00000483926, ENST00000485269, ENST00000490170, ENST00000496001, ENST00000543823, ENST00000615284, ENST00000616558, ENST00000618673, ENST00000887628, ENST00000887629, ENST00000887630, ENST00000887631, ENST00000887632, ENST00000887633, ENST00000970487, ENST00000970488, ENST00000970489, ENST00000970490, ENST00000970491

RefSeq mRNA: 2 — MANE Select: NM_001193308 NM_001193308, NM_032872

CCDS: CCDS298, CCDS53286

Canonical transcript exons

ENST00000616558 — 15 exons

Exon	Start	End
ENSE00000956278	27349652	27349765
ENSE00001218694	27349398	27349498
ENSE00001218786	27342022	27342150
ENSE00003471185	27351456	27351555
ENSE00003480251	27351258	27351336
ENSE00003510517	27347808	27347880
ENSE00003518835	27345297	27345525
ENSE00003530134	27350794	27350952
ENSE00003539518	27350389	27350485
ENSE00003555660	27347967	27348012
ENSE00003567581	27349972	27350132
ENSE00003587554	27353283	27353488
ENSE00003617072	27347421	27347569
ENSE00003652059	27349080	27349152
ENSE00003724726	27353713	27353932

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 99.20.

FANTOM5 (CAGE): breadth broad, TPM avg 16.4759 / max 306.0070, expressed in 902 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1704	16.3965	901
1705	0.0794	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.20	gold quality
lower esophagus mucosa	UBERON:0035834	98.80	gold quality
right uterine tube	UBERON:0001302	98.02	gold quality
body of pancreas	UBERON:0001150	98.01	gold quality
skin of abdomen	UBERON:0001416	97.68	gold quality
upper arm skin	UBERON:0004263	97.51	gold quality
esophagus mucosa	UBERON:0002469	97.46	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.10	gold quality
skin of leg	UBERON:0001511	96.86	gold quality
gingival epithelium	UBERON:0001949	96.71	gold quality
zone of skin	UBERON:0000014	96.28	gold quality
gingiva	UBERON:0001828	96.28	gold quality
spleen	UBERON:0002106	96.10	gold quality
cerebellar hemisphere	UBERON:0002245	95.58	gold quality
cerebellar cortex	UBERON:0002129	95.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.35	gold quality
blood	UBERON:0000178	95.32	gold quality
pharyngeal mucosa	UBERON:0000355	95.21	gold quality
mouth mucosa	UBERON:0003729	95.20	gold quality
mammalian vulva	UBERON:0000997	95.16	gold quality
minor salivary gland	UBERON:0001830	95.02	gold quality
saliva-secreting gland	UBERON:0001044	94.52	gold quality
cerebellum	UBERON:0002037	94.47	gold quality
trachea	UBERON:0003126	94.46	gold quality
superior surface of tongue	UBERON:0007371	94.31	gold quality
nasal cavity epithelium	UBERON:0005384	94.20	gold quality
oral cavity	UBERON:0000167	94.16	gold quality
upper leg skin	UBERON:0004262	93.95	gold quality
bone marrow cell	CL:0002092	93.64	gold quality
esophagus squamous epithelium	UBERON:0006920	93.53	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.45
E-MTAB-6678	yes	9.36
E-MTAB-7606	no	2164.38
E-CURD-112	no	2.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

Literature-anchored findings (GeneRIF, showing 10)

• Jfc1/synaptotagmin-like protein 1 (Slp1) contains an N-terminal Slp homology domain (SHD) (PMID: 11327731). The SHD of Slp1/Jfc1 specifically and directly binds the GTP-bound form of Rab27A (J. Biol. Chem. 277, (2002) 9212-9218; PMID: 11773082). (PMID:11773082)
• transcriptional activation of JFC1 by the TNFalpha/NF-kappaB pathway is significant in prostate carcinoma cell lines (PMID:12137562)
• evidence that JFC1 differentially regulates the secretion of PSAP and PSA, and that Rab27a and PI3K play a central role in the exocytosis of prostate-specific markers (PMID:16004602)
• These results suggest that both Slp1 and Slp2-a may form part of a docking complex, capturing secretory lysosomes at the immunological synapse. (PMID:18266782)
• Slp1 inhibits dense granule secretion in platelets and that Rap1GAP2 modulates secretion by binding to Slp1. (PMID:19528539)
• during exocytosis, actin depolymerization commences near the secretory organelle, not the plasma membrane, and secretory granules use a JFC1- and GMIP-dependent molecular mechanism to traverse cortical actin. (PMID:22438581)
• Cdk2 also binds the N-terminal domain of Fbw7-gamma as well as SLP-1. (PMID:23082202)
• results reveal that MEIS1, through induction of SYTL1, promotes leukemogenesis and supports leukemic cell homing and engraftment, facilitating interactions between leukemic cells and bone marrow stroma. (PMID:27018596)
• ELK1 suppresses SYTL1 expression by recruiting HDAC2 in bladder cancer progression. (PMID:36107384)
• WTAP enhances the instability of SYTL1 mRNA caused by YTHDF2 in bladder cancer. (PMID:37933909)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sytl1	ENSDARG00000070094
mus_musculus	Sytl1	ENSMUSG00000028860
rattus_norvegicus	Sytl1	ENSRNOG00000008600

Paralogs (31): SYT7 (ENSG00000011347), SYT13 (ENSG00000019505), SYT1 (ENSG00000067715), RPH3A (ENSG00000089169), SYTL4 (ENSG00000102362), SYT17 (ENSG00000103528), SYT10 (ENSG00000110975), SYT5 (ENSG00000129990), SYT11 (ENSG00000132718), SYT4 (ENSG00000132872), SYT6 (ENSG00000134207), SYTL2 (ENSG00000137501), SYT16 (ENSG00000139973), SYT14 (ENSG00000143469), SYT2 (ENSG00000143858), SYTL5 (ENSG00000147041), SYT8 (ENSG00000149043), DOC2A (ENSG00000149927), SYTL3 (ENSG00000164674), TC2N (ENSG00000165929), SYT9 (ENSG00000170743), SYT12 (ENSG00000173227), RPH3AL (ENSG00000181031), C2CD4C (ENSG00000183186), C2CD4A (ENSG00000198535), SYT15 (ENSG00000204176), C2CD4B (ENSG00000205502), SYT3 (ENSG00000213023), C2CD4D (ENSG00000225556), DOC2B (ENSG00000272636), SYT15B (ENSG00000277758)

Protein

Protein identifiers

Synaptotagmin-like protein 1 — Q8IYJ3 (reviewed: Q8IYJ3)

Alternative names: Exophilin-7, Protein JFC1

All UniProt accessions (3): Q8IYJ3, A0A087X1N4, Q5SSC6

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in vesicle trafficking. Binds phosphatidylinositol 3,4,5-trisphosphate. Acts as a RAB27A effector protein and may play a role in cytotoxic granule exocytosis in lymphocytes.

Subunit / interactions. Monomer. Binds NRXN1. Binds RAB27A that has been activated by GTP-binding via its N-terminus. Binds NCF2.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in bone marrow and lymphoid tissues. Detected at lower levels in cerebellum, occipital lobe, prostate, stomach, kidney, appendix, lung and trachea. Expressed in cytotoxic T-lymphocytes (CTL).

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IYJ3-1	1	yes
Q8IYJ3-2	2

RefSeq proteins (2): NP_001180237, NP_116261 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR010911	Rab_BD	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR043567	SYTL1-5_C2B	Domain

Pfam: PF00168

UniProt features (14 total): domain 3, sequence conflict 3, compositionally biased region 3, region of interest 2, chain 1, splice variant 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYJ3-F1	72.97	0.42

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 216

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8854214	TBC/RABGAPs
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9007101	Rab regulation of trafficking

MSigDB gene sets: 0 (showing top):

GO Biological Process (2): intracellular protein transport (GO:0006886), exocytosis (GO:0006887)

GO Molecular Function (3): small GTPase binding (GO:0031267), neurexin family protein binding (GO:0042043), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), microvillus membrane (GO:0031528), melanosome (GO:0042470), extracellular exosome (GO:0070062), exocytic vesicle (GO:0070382), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Rab regulation of trafficking	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
intracellular protein localization	1
protein transport	1
intracellular transport	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
GTPase binding	1
signaling receptor binding	1
binding	1
membrane	1
cell periphery	1
microvillus	1
cell projection membrane	1
pigment granule	1
extracellular vesicle	1
transport vesicle	1
secretory vesicle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYTL1	RAB27A	P51159	983
SYTL1	MYRIP	Q8NFW9	903
SYTL1	RAB27B	O00194	854
SYTL1	MYO5A	Q9Y4I1	819
SYTL1	GMIP	Q9P107	682
SYTL1	NCF2	P19878	663
SYTL1	MLPH	Q9BV36	662
SYTL1	RAB3A	P20336	650
SYTL1	STXBP2	Q15833	616
SYTL1	STX3	Q13277	599
SYTL1	UNC13D	Q70J99	583
SYTL1	NCF1	P14598	572
SYTL1	VAMP8	Q9BV40	570
SYTL1	RPH3AL	Q9UNE2	536
SYTL1	DPYSL2	Q16555	493

IntAct

23 interactions, top by confidence:

A	B	Type	Score
RAB27A	SYTL1	psi-mi:“MI:0915”(physical association)	0.740
RAB27B	GBA1	psi-mi:“MI:0914”(association)	0.530
SYTL1	E6	psi-mi:“MI:0915”(physical association)	0.370
RAB27B	GBA1	psi-mi:“MI:0914”(association)	0.350
RAB27A	GTPBP1	psi-mi:“MI:0914”(association)	0.350
RAB27A	ATE1	psi-mi:“MI:0914”(association)	0.350
RAB27B	MYH7B	psi-mi:“MI:0914”(association)	0.350
RAB27A	SYTL1	psi-mi:“MI:0915”(physical association)	0.000
SYTL1		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (32): SYTL1 (Affinity Capture-MS), SYTL1 (Affinity Capture-RNA), SYTL1 (Biochemical Activity), SYTL1 (Affinity Capture-Western), RAB27A (Reconstituted Complex), SYTL1 (Affinity Capture-Western), SYTL1 (Affinity Capture-MS), SYTL1 (Two-hybrid), NCF2 (Reconstituted Complex), NCF1 (Reconstituted Complex), SYTL1 (Two-hybrid), SYTL1 (Two-hybrid), RAB27A (Affinity Capture-Western), RAB27A (Reconstituted Complex), SYTL1 (Affinity Capture-Western)

ESM2 similar proteins: A1L3T7, A2A3L6, A4IFI1, A7E3N7, A8MYJ7, A8VU90, O94761, O94812, O95153, O95382, P97680, Q0P5G1, Q13671, Q14154, Q3UYR4, Q4V896, Q53GL7, Q569K6, Q58CQ5, Q58EX7, Q66H85, Q6DT37, Q6F5E8, Q6ZVH7, Q76MJ5, Q7TNF8, Q7Z3H0, Q80UU1, Q80UW5, Q8BWA8, Q8BXP5, Q8BYG0, Q8CIE4, Q8CJ00, Q8IYJ3, Q8NAG6, Q8TE82, Q91WA6, Q91WE1, Q921Q7

Diamond homologs: A0A075F932, A0FGR8, A0FGR9, A4IJ05, A6QP06, O00443, O00445, O00750, O08625, O08835, O35681, P04409, P05128, P05129, P10829, P21521, P21579, P21707, P24505, P24506, P24507, P29101, P34693, P40748, P40749, P41823, P46096, P46097, P47191, P47708, P47709, P47861, P48018, P50232, P59926, P63318, P63319, P70169, P70610, P70611

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AKT1	“down-regulates quantity”	SYTL1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2161 predictions. Top by Δscore:

Variant	Effect	Δscore
1:27347553:G:GT	donor_gain	1.0000
1:27347567:GGG:G	donor_gain	1.0000
1:27347568:GGG:G	donor_gain	1.0000
1:27349076:TCAG:T	acceptor_loss	1.0000
1:27349077:CAGG:C	acceptor_loss	1.0000
1:27349078:A:AG	acceptor_gain	1.0000
1:27349078:A:AT	acceptor_loss	1.0000
1:27349078:AG:A	acceptor_gain	1.0000
1:27349079:G:GA	acceptor_loss	1.0000
1:27349079:G:GG	acceptor_gain	1.0000
1:27349079:GG:G	acceptor_gain	1.0000
1:27349148:GGAAG:G	donor_gain	1.0000
1:27349149:GAAGG:G	donor_gain	1.0000
1:27349150:A:T	donor_gain	1.0000
1:27349153:G:GA	donor_loss	1.0000
1:27349153:G:GG	donor_gain	1.0000
1:27349154:T:G	donor_loss	1.0000
1:27349393:CCCA:C	acceptor_loss	1.0000
1:27349394:CCAG:C	acceptor_loss	1.0000
1:27349395:CA:C	acceptor_loss	1.0000
1:27349396:A:AG	acceptor_gain	1.0000
1:27349396:AG:A	acceptor_loss	1.0000
1:27349397:G:GG	acceptor_gain	1.0000
1:27349970:A:T	acceptor_loss	1.0000
1:27349971:GC:G	acceptor_gain	1.0000
1:27349971:GCT:G	acceptor_gain	1.0000
1:27349971:GCTGA:G	acceptor_gain	1.0000
1:27350128:GACCC:G	donor_gain	1.0000
1:27350130:CCC:C	donor_gain	1.0000
1:27350133:G:GG	donor_gain	1.0000

AlphaMissense

3622 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:27350394:T:A	V305D	0.998
1:27350398:A:C	K306N	0.998
1:27350398:A:T	K306N	0.998
1:27350428:G:C	K316N	0.997
1:27350428:G:T	K316N	0.997
1:27350396:A:G	K306E	0.996
1:27353476:A:C	S513R	0.996
1:27353478:C:A	S513R	0.996
1:27353478:C:G	S513R	0.996
1:27353739:T:A	W526R	0.996
1:27353739:T:C	W526R	0.996
1:27350397:A:T	K306I	0.995
1:27350434:G:C	K318N	0.994
1:27350434:G:T	K318N	0.994
1:27350469:T:C	F330S	0.994
1:27350845:T:A	W353R	0.994
1:27350845:T:C	W353R	0.994
1:27350882:G:T	G365V	0.994
1:27353357:T:C	F473S	0.994
1:27353772:T:A	W537R	0.994
1:27353772:T:C	W537R	0.994
1:27353804:G:C	W547C	0.994
1:27353804:G:T	W547C	0.994
1:27350094:C:G	C290W	0.993
1:27350468:T:C	F330L	0.993
1:27350470:C:A	F330L	0.993
1:27350470:C:G	F330L	0.993
1:27350881:G:C	G365R	0.993
1:27350882:G:A	G365D	0.993
1:27353414:C:A	A492D	0.993

dbSNP variants (sampled 300 via entrez): RS1000007136 (1:27351770 T>A), RS1000238134 (1:27346181 G>A), RS1000522014 (1:27348952 C>A,G,T), RS1000525017 (1:27345790 T>C), RS1000648662 (1:27342826 C>G,T), RS1000660200 (1:27342543 G>A), RS1000709032 (1:27342259 A>C,G), RS1000977729 (1:27348794 G>A), RS1001142799 (1:27344277 A>T), RS1002033889 (1:27349295 G>A,C,T), RS1002090667 (1:27343094 C>G,T), RS1002245585 (1:27347331 T>C), RS1002366852 (1:27345795 C>T), RS1002368812 (1:27341491 G>A), RS1002518939 (1:27346209 A>G)

Disease associations

OMIM: gene MIM:608042 | 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
GCST005212_22	Asthma	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases methylation, increases expression, increases methylation	8
Benzo(a)pyrene	decreases methylation, increases expression	7
Estradiol	affects expression, affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	affects cotreatment, increases expression, decreases expression	2
Cyclosporine	increases expression	2
Particulate Matter	decreases expression	2
aristolochic acid I	increases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	decreases expression	1
beta-lapachone	increases expression	1
perfluorooctanoic acid	increases expression	1
cupric chloride	decreases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
deguelin	increases expression	1
entinostat	increases expression	1
monomethylarsonous acid	decreases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
thifluzamide	increases expression	1
pyrachlostrobin	increases expression	1
jinfukang	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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