SYTL3

Summary

SYTL3 (synaptotagmin like 3, HGNC:15587) is a protein-coding gene on chromosome 6q25.3, encoding Synaptotagmin-like protein 3 (Q4VX76). May act as Rab effector protein and play a role in vesicle trafficking.

The protein encoded by this gene belongs to a family of peripheral membrane proteins that play a role in vesicular trafficking. This protein binds phospholipids in the presence of calcium ions. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 94120 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 123 total
• MANE Select transcript: NM_001242394

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15587
Approved symbol	SYTL3
Name	synaptotagmin like 3
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Aliases	SLP3, exophilin-6
Ensembl gene	ENSG00000164674
Ensembl biotype	protein_coding
OMIM	620973
Entrez	94120

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 20 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000360448, ENST00000367081, ENST00000469735, ENST00000611299, ENST00000852390, ENST00000852391, ENST00000852392, ENST00000852393, ENST00000852394, ENST00000852395, ENST00000852396, ENST00000945460, ENST00000945461, ENST00000945462, ENST00000945463, ENST00000945464, ENST00000945465, ENST00000945466, ENST00000945467, ENST00000945468, ENST00000945469

RefSeq mRNA: 5 — MANE Select: NM_001242394 NM_001009991, NM_001242384, NM_001242394, NM_001242395, NM_001318745

CCDS: CCDS34563, CCDS56458

Canonical transcript exons

ENST00000611299 — 18 exons

Exon	Start	End
ENSE00001086525	158760640	158760745
ENSE00001086526	158745480	158745658
ENSE00001086527	158757211	158757381
ENSE00001204228	158763304	158763509
ENSE00001204232	158762076	158762178
ENSE00001213263	158751928	158752030
ENSE00001339007	158718087	158718211
ENSE00001339008	158713800	158713878
ENSE00001339009	158708322	158708391
ENSE00001339010	158725503	158725637
ENSE00001339011	158707230	158707281
ENSE00001366609	158665395	158665613
ENSE00001407958	158651753	158651842
ENSE00001849133	158661269	158661385
ENSE00002243418	158662750	158663378
ENSE00003739746	158682925	158682989
ENSE00003912841	158650054	158650078
ENSE00003914969	158764495	158764871

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 96.74.

FANTOM5 (CAGE): breadth broad, TPM avg 9.7634 / max 744.2618, expressed in 757 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70848	7.2339	630
70861	0.4121	79
70862	0.3220	103
70860	0.2864	43
70859	0.2816	49
70850	0.2504	70
70858	0.2365	23
70849	0.2209	80
70863	0.2175	83
70856	0.2064	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.74	gold quality
oocyte	CL:0000023	93.90	gold quality
bronchial epithelial cell	CL:0002328	93.19	gold quality
bronchus	UBERON:0002185	92.29	gold quality
granulocyte	CL:0000094	91.40	gold quality
right uterine tube	UBERON:0001302	89.89	gold quality
blood	UBERON:0000178	89.46	gold quality
nasal cavity epithelium	UBERON:0005384	87.01	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.82	gold quality
right lung	UBERON:0002167	83.93	gold quality
thyroid gland	UBERON:0002046	83.51	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.27	gold quality
spleen	UBERON:0002106	83.26	gold quality
left lobe of thyroid gland	UBERON:0001120	83.13	gold quality
epithelium of nasopharynx	UBERON:0001951	83.12	gold quality
right lobe of thyroid gland	UBERON:0001119	82.86	gold quality
thymus	UBERON:0002370	82.84	gold quality
leukocyte	CL:0000738	82.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.35	gold quality
monocyte	CL:0000576	82.20	gold quality
parotid gland	UBERON:0001831	81.98	gold quality
muscle of leg	UBERON:0001383	81.00	gold quality
apex of heart	UBERON:0002098	80.94	gold quality
gastrocnemius	UBERON:0001388	80.65	gold quality
nasal cavity mucosa	UBERON:0001826	79.65	gold quality
upper lobe of left lung	UBERON:0008952	79.48	gold quality
kidney epithelium	UBERON:0004819	79.35	gold quality
saliva-secreting gland	UBERON:0001044	78.81	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	2816.93
E-CURD-120	yes	1237.36
E-HCAD-36	yes	561.46
E-MTAB-8142	yes	65.52
E-CURD-46	yes	58.42
E-CURD-88	yes	48.34
E-CURD-122	yes	46.71
E-GEOD-135922	yes	30.01
E-MTAB-6678	yes	25.69
E-ANND-3	yes	20.31
E-HCAD-1	yes	18.19
E-MTAB-10553	yes	12.29
E-MTAB-9067	yes	12.01
E-MTAB-8410	yes	9.44
E-MTAB-9801	yes	5.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting SYTL3, 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-4803	99.98	71.99	3117
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-3188	98.58	65.60	878

Literature-anchored findings (GeneRIF, showing 2)

• Synaptotagmin-like protein 3-a (Slp3-a) contains an N-terminal Slp homology domain (SHD) (PMID: 11327731). The SHD of Slp3-a specifically and directly binds the GTP-bound form of Rab27A. (PMID:11773082)
• Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment. (PMID:33657377)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sytl3	ENSDARG00000043468
mus_musculus	Sytl3	ENSMUSG00000041831
rattus_norvegicus	Sytl3	ENSRNOG00000018321

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), SYTL1 (ENSG00000142765), SYT14 (ENSG00000143469), SYT2 (ENSG00000143858), SYTL5 (ENSG00000147041), SYT8 (ENSG00000149043), DOC2A (ENSG00000149927), 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 3 — Q4VX76 (reviewed: Q4VX76)

Alternative names: Exophilin-6

All UniProt accessions (1): Q4VX76

UniProt curated annotations — full annotation on UniProt →

Function. May act as Rab effector protein and play a role in vesicle trafficking. Binds phospholipids in the presence of calcium ions.

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

Subcellular location. Endomembrane system.

Isoforms (2)

UniProt ID	Names	Canonical?
Q4VX76-1	1	yes
Q4VX76-2	2

RefSeq proteins (5): NP_001009991, NP_001229313, NP_001229323, NP_001229324, NP_001305674 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR010911	Rab_BD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR035892	C2_domain_sf	Homologous_superfamily
IPR041282	FYVE_2	Domain
IPR043567	SYTL1-5_C2B	Domain

Pfam: PF00168, PF02318

UniProt features (9 total): domain 3, sequence variant 3, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4VX76-F1	71.86	0.32

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, chr6q25, GOBP_EXOCYTOSIS, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_SECRETION, BROWN_MYELOID_CELL_DEVELOPMENT_DN, GOMF_SIGNALING_RECEPTOR_BINDING, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_EXOCYTIC_VESICLE, GOCC_SECRETORY_VESICLE, LEIN_CEREBELLUM_MARKERS, GOMF_NEUREXIN_FAMILY_PROTEIN_BINDING

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

GO Molecular Function (5): calcium-dependent phospholipid binding (GO:0005544), small GTPase binding (GO:0031267), neurexin family protein binding (GO:0042043), protein binding (GO:0005515), phospholipid binding (GO:0005543)

GO Cellular Component (4): plasma membrane (GO:0005886), exocytic vesicle (GO:0070382), endomembrane system (GO:0012505), membrane (GO:0016020)

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
phospholipid binding	1
GTPase binding	1
signaling receptor binding	1
binding	1
lipid binding	1
membrane	1
cell periphery	1
transport vesicle	1
secretory vesicle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYTL3	RAB27A	P51159	773
SYTL3	STXBP2	Q15833	656
SYTL3	STX3	Q13277	608
SYTL3	RAB3A	P20336	603
SYTL3	TMEM154	Q6P9G4	574
SYTL3	VAMP8	Q9BV40	562
SYTL3	UNC13D	Q70J99	531
SYTL3	MYO5A	Q9Y4I1	512
SYTL3	RAB27B	O00194	500
SYTL3	TMEM38A	Q9H6F2	494
SYTL3	LIN9	Q5TKA1	477
SYTL3	MYH9	P35579	444
SYTL3	ZSCAN16	Q9H4T2	427
SYTL3	DLGAP1	P78335	426
SYTL3	ZMAT5	Q9UDW3	426

IntAct

16 interactions, top by confidence:

A	B	Type	Score
RAB27A	SYTL3	psi-mi:“MI:0915”(physical association)	0.740
OAZ2	SYTL3	psi-mi:“MI:0915”(physical association)	0.560
SYTL3	ANKRD11	psi-mi:“MI:0915”(physical association)	0.560
RAB27B	GBA1	psi-mi:“MI:0914”(association)	0.530
SYTL3	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
RAB27A	GTPBP1	psi-mi:“MI:0914”(association)	0.350
RAB27A	ATE1	psi-mi:“MI:0914”(association)	0.350
RAB27A	SYTL3	psi-mi:“MI:0915”(physical association)	0.000
ANKRD11	SYTL3	psi-mi:“MI:0915”(physical association)	0.000
SYTL3	barA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): SYTL3 (Affinity Capture-MS), SYTL3 (Affinity Capture-Western), SYTL3 (Two-hybrid), ANKRD11 (Two-hybrid), OAZ2 (Two-hybrid), RAB27A (Affinity Capture-Western), RAB10 (Affinity Capture-Western), SYTL3 (Affinity Capture-Western), SYTL3 (Reconstituted Complex), SYTL3 (Affinity Capture-MS), SYTL3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JXN2, A2AWP8, O88842, O95267, P29590, P52734, P98174, Q1LY10, Q29RM4, Q2TBA3, Q3TAA7, Q3U0J8, Q3UTZ3, Q496Y0, Q4VX76, Q568M3, Q58D15, Q5BIM1, Q5JSP0, Q5R5M3, Q5R5T1, Q5REJ9, Q5W0U4, Q68FF6, Q69Z89, Q69ZK0, Q6PFY8, Q7TNM2, Q7Z4K8, Q7Z5H3, Q7Z6J4, Q80V85, Q8BY35, Q8BZ52, Q8C190, Q8N1F8, Q8TCU6, Q8WVR3, Q96JH8, Q99N48

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3749 predictions. Top by Δscore:

Variant	Effect	Δscore
6:158644683:T:TA	donor_gain	1.0000
6:158651740:T:A	acceptor_gain	1.0000
6:158661268:GA:G	acceptor_gain	1.0000
6:158662745:T:A	acceptor_gain	1.0000
6:158662745:TGCAG:T	acceptor_loss	1.0000
6:158662746:GCAG:G	acceptor_loss	1.0000
6:158662747:CAG:C	acceptor_loss	1.0000
6:158662748:A:AG	acceptor_gain	1.0000
6:158662748:AGGT:A	acceptor_loss	1.0000
6:158662749:G:GA	acceptor_gain	1.0000
6:158662749:GGT:G	acceptor_gain	1.0000
6:158662809:G:GT	donor_gain	1.0000
6:158662810:A:T	donor_gain	1.0000
6:158665386:G:A	acceptor_gain	1.0000
6:158682922:CAG:C	acceptor_loss	1.0000
6:158682923:A:AC	acceptor_loss	1.0000
6:158682923:A:AG	acceptor_gain	1.0000
6:158682924:G:GG	acceptor_gain	1.0000
6:158682924:G:GT	acceptor_loss	1.0000
6:158682924:GGA:G	acceptor_gain	1.0000
6:158682924:GGAAT:G	acceptor_gain	1.0000
6:158682990:G:GA	donor_loss	1.0000
6:158745479:GGGAA:G	acceptor_gain	1.0000
6:158745659:G:GG	donor_gain	1.0000
6:158751923:CCTA:C	acceptor_loss	1.0000
6:158751924:CTAG:C	acceptor_loss	1.0000
6:158751925:TA:T	acceptor_loss	1.0000
6:158751926:A:AT	acceptor_loss	1.0000
6:158757209:A:AG	acceptor_gain	1.0000
6:158757209:A:G	acceptor_loss	1.0000

AlphaMissense

3968 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:158762172:T:A	V504D	0.994
6:158763377:T:A	W531R	0.992
6:158763377:T:C	W531R	0.992
6:158763379:G:C	W531C	0.990
6:158763379:G:T	W531C	0.990
6:158763447:T:A	V554D	0.989
6:158763441:T:C	L552S	0.985
6:158764575:T:A	W602R	0.984
6:158764575:T:C	W602R	0.984
6:158760689:T:A	V453D	0.983
6:158764545:T:A	W592R	0.983
6:158764545:T:C	W592R	0.983
6:158757299:G:T	G409V	0.981
6:158762168:T:C	F503L	0.981
6:158762170:T:A	F503L	0.981
6:158762170:T:G	F503L	0.981
6:158762177:G:C	G506R	0.981
6:158752013:T:C	F374L	0.980
6:158752015:T:A	F374L	0.980
6:158752015:T:G	F374L	0.980
6:158665591:T:A	C103S	0.979
6:158665592:G:C	C103S	0.979
6:158665591:T:C	C103R	0.977
6:158757299:G:A	G409E	0.977
6:158763309:T:C	L508P	0.977
6:158763396:T:C	F537S	0.977
6:158665555:T:A	C91S	0.976
6:158665556:G:C	C91S	0.976
6:158751937:G:C	K348N	0.976
6:158751937:G:T	K348N	0.976

dbSNP variants (sampled 300 via entrez): RS1000005766 (6:158658667 A>G), RS1000007121 (6:158733560 C>G,T), RS1000011392 (6:158697782 C>T), RS1000044152 (6:158711955 C>G,T), RS1000080977 (6:158739738 C>T), RS1000119743 (6:158692352 T>C), RS1000191354 (6:158764146 C>T), RS1000202181 (6:158678878 T>A), RS1000219670 (6:158762542 C>T), RS1000221112 (6:158764266 C>T), RS1000235014 (6:158728901 G>A), RS1000236218 (6:158691725 C>G,T), RS1000277540 (6:158652959 G>A), RS1000281097 (6:158739514 A>G), RS1000289264 (6:158663692 T>C)

Disease associations

OMIM: gene MIM:620973 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003127_11	Lipoprotein (a) levels	2.000000e-13
GCST008829_9	Neuritic plaque	4.000000e-06
GCST009134_1	Peripheral artery disease (borderline)	8.000000e-07
GCST010002_339	Refractive error	5.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006925	lipoprotein A measurement
EFO:0006798	neuritic plaque measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Tretinoin	increases expression	3
Nickel	increases expression	2
Valproic Acid	increases expression, increases methylation	2
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	affects expression, increases abundance	1
Calcitriol	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Demecolcine	increases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Methapyrilene	increases methylation	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Ozone	affects expression, increases abundance	1

Clinical trials (associated diseases)

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