SYTL5

Summary

SYTL5 (synaptotagmin like 5, HGNC:15589) is a protein-coding gene on chromosome Xp11.4, encoding Synaptotagmin-like protein 5 (Q8TDW5). May act as Rab effector protein and play a role in vesicle trafficking.

The protein encoded by this gene belongs to the synaptotagmin-like (Slp) protein family, which contains a unique homology domain at the N-terminus, referred to as the Slp homology domain (SHD). The SHD functions as a binding site for Rab27A, which plays a role in protein transport. Expression of this gene is restricted to placenta and liver, suggesting that it might be involved in Rab27A-dependent membrane trafficking in specific tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 94122 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 173 total
• MANE Select transcript: NM_138780

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15589
Approved symbol	SYTL5
Name	synaptotagmin like 5
Location	Xp11.4
Locus type	gene with protein product
Status	Approved
Aliases	Slp5
Ensembl gene	ENSG00000147041
Ensembl biotype	protein_coding
OMIM	301126
Entrez	94122

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000297875, ENST00000456733, ENST00000891605, ENST00000891606, ENST00000891607, ENST00000891608, ENST00000891609, ENST00000962258

RefSeq mRNA: 3 — MANE Select: NM_138780 NM_001163334, NM_001163335, NM_138780

CCDS: CCDS14244, CCDS55399

Canonical transcript exons

ENST00000297875 — 17 exons

Exon	Start	End
ENSE00000978453	38108600	38108699
ENSE00001025761	38122080	38122215
ENSE00001025762	38110321	38110482
ENSE00001090932	38125298	38125506
ENSE00001090934	38120358	38120466
ENSE00001090950	38106593	38106771
ENSE00001128382	38102342	38102434
ENSE00001163459	38126588	38128816
ENSE00001163469	38096134	38096234
ENSE00001192148	38094295	38094424
ENSE00001192153	38089446	38089587
ENSE00001192157	38076567	38076701
ENSE00001192164	38073590	38073698
ENSE00001192166	38072047	38072162
ENSE00001192171	38054213	38054422
ENSE00001431334	38033534	38034008
ENSE00001477956	38006553	38006668

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 96.37.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2296 / max 20.1260, expressed in 112 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195929	0.1563	80
195930	0.0733	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	96.37	gold quality
ileal mucosa	UBERON:0000331	93.11	gold quality
palpebral conjunctiva	UBERON:0001812	92.14	gold quality
nasal cavity epithelium	UBERON:0005384	86.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.66	gold quality
mucosa of sigmoid colon	UBERON:0004993	82.77	gold quality
nucleus accumbens	UBERON:0001882	81.90	gold quality
colonic mucosa	UBERON:0000317	81.66	gold quality
right adrenal gland	UBERON:0001233	80.83	gold quality
hypothalamus	UBERON:0001898	80.12	gold quality
right adrenal gland cortex	UBERON:0035827	79.84	gold quality
amygdala	UBERON:0001876	79.66	gold quality
left adrenal gland	UBERON:0001234	79.13	gold quality
caudate nucleus	UBERON:0001873	78.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.02	silver quality
left adrenal gland cortex	UBERON:0035825	78.01	gold quality
placenta	UBERON:0001987	77.93	gold quality
adrenal cortex	UBERON:0001235	77.49	gold quality
Ammon’s horn	UBERON:0001954	76.72	gold quality
putamen	UBERON:0001874	76.32	gold quality
bronchial epithelial cell	CL:0002328	75.97	gold quality
adrenal gland	UBERON:0002369	75.66	gold quality
epithelial cell of pancreas	CL:0000083	74.68	silver quality
bronchus	UBERON:0002185	74.38	gold quality
esophagus squamous epithelium	UBERON:0006920	74.06	gold quality
body of pancreas	UBERON:0001150	73.97	gold quality
temporal lobe	UBERON:0001871	73.27	gold quality
amniotic fluid	UBERON:0000173	72.41	gold quality
anterior cingulate cortex	UBERON:0009835	72.01	gold quality
mucosa of transverse colon	UBERON:0004991	70.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

117 targeting SYTL5, 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-432-3P	100.00	67.86	705
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 4)

• Synaptotagmin-like protein 5 (Slp5) contains an N-terminal Slp homology domain (SHD) (PMID: 11327731). The SHD of Slp5 specifically and directly binds the GTP-bound form of Rab27A. (PMID:12051743)
• molecular cloning of slp5:a novel Rab27A effector with C-terminal tandem C2 domains (PMID:12051743)
• These observations decisively prove that Rab27a inhibits ENaC function through a complex mechanism that involves GTP/GDP status, and protein-protein interactions involving Munc13-4 and SLP-5 effector proteins. (PMID:16630545)
• SYTL5 Promotes Papillary Thyroid Carcinoma Progression by Enhancing Activation of the NF-kappaB Signaling Pathway. (PMID:36378561)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sytl5	ENSDARG00000062135
mus_musculus	Sytl5	ENSMUSG00000054453
rattus_norvegicus	Sytl5	ENSRNOG00000003585

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), 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 5 — Q8TDW5 (reviewed: Q8TDW5)

All UniProt accessions (1): Q8TDW5

UniProt curated annotations — full annotation on UniProt →

Function. May act as Rab effector protein and play a role in vesicle trafficking. Binds phospholipids.

Subunit / interactions. Binds RAB27A that has been activated by GTP-binding, and possibly also RAB3A and RAB6A.

Subcellular location. Membrane.

Tissue specificity. Highly expressed in placenta and liver.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TDW5-1	1	yes
Q8TDW5-2	2

RefSeq proteins (3): NP_001156806, NP_001156807, NP_620135* (*=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
IPR037303	SLP-4/5_C2A	Domain
IPR041282	FYVE_2	Domain
IPR042783	SYTL5_FYVE	Domain
IPR043567	SYTL1-5_C2B	Domain

Pfam: PF00168, PF02318

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDW5-F1	65.97	0.22

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): 147

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOZGIT_ESR1_TARGETS_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, LHX3_01, GOMF_GTPASE_BINDING, GOBP_EXOCYTOSIS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_SECRETION, GOMF_SIGNALING_RECEPTOR_BINDING, GOCC_EXOCYTIC_VESICLE

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

GO Molecular Function (6): phospholipid binding (GO:0005543), zinc ion binding (GO:0008270), small GTPase binding (GO:0031267), neurexin family protein binding (GO:0042043), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): plasma membrane (GO:0005886), exocytic vesicle (GO:0070382), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein localization	1
protein transport	1
intracellular transport	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
lipid binding	1
transition metal ion binding	1
GTPase binding	1
signaling receptor binding	1
binding	1
cation binding	1
membrane	1
cell periphery	1
transport vesicle	1
secretory vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYTL5	RAB27A	P51159	701
SYTL5	RAB3A	P20336	658
SYTL5	STXBP2	Q15833	635
SYTL5	STX3	Q13277	633
SYTL5	RAB27B	O00194	586
SYTL5	VAMP8	Q9BV40	582
SYTL5	UNC13D	Q70J99	571
SYTL5	MYO5A	Q9Y4I1	522
SYTL5	EXPH5	Q8NEV8	463
SYTL5	MYH9	P35579	452
SYTL5	RAB8B	Q92930	445
SYTL5	RAB8A	P24407	409
SYTL5	RIMS1	Q86UR5	407
SYTL5	FAM47B	Q8NA70	400
SYTL5	SATL1	Q86VE3	396

IntAct

25 interactions, top by confidence:

A	B	Type	Score
SYTL5	RAB27B	psi-mi:“MI:0915”(physical association)	0.850
RAB27B	SYTL5	psi-mi:“MI:0915”(physical association)	0.850
SYTL5	RAB27B	psi-mi:“MI:0914”(association)	0.850
SYTL5	CEP70	psi-mi:“MI:0915”(physical association)	0.670
CEP70	SYTL5	psi-mi:“MI:0915”(physical association)	0.670
SYTL5	WAC	psi-mi:“MI:0915”(physical association)	0.560
WAC	SYTL5	psi-mi:“MI:0915”(physical association)	0.560
SYTL5	Rab3a	psi-mi:“MI:0407”(direct interaction)	0.540
Rab3a	SYTL5	psi-mi:“MI:0915”(physical association)	0.540
SYTL5	Rab6a	psi-mi:“MI:0407”(direct interaction)	0.540
SYTL5	Rab6a	psi-mi:“MI:0915”(physical association)	0.540
Rab27a	SYTL5	psi-mi:“MI:0407”(direct interaction)	0.540
SYTL5	Rab27a	psi-mi:“MI:0915”(physical association)	0.540
RAB27B	GBA1	psi-mi:“MI:0914”(association)	0.530
RAB27B	GBA1	psi-mi:“MI:0914”(association)	0.350
SYTL5	CCDC85C	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

BioGRID (30): SYTL5 (Two-hybrid), SYTL5 (Two-hybrid), SYTL5 (Two-hybrid), SYTL5 (Affinity Capture-MS), SYTL5 (Affinity Capture-Western), SYTL5 (Two-hybrid), SYTL5 (Two-hybrid), SYTL5 (Two-hybrid), SYTL5 (Two-hybrid), YIF1A (Two-hybrid), SYTL5 (Two-hybrid), SYTL5 (Proximity Label-MS), SYTL5 (Proximity Label-MS), RAB27A (Reconstituted Complex), RAB3A (Reconstituted Complex)

ESM2 similar proteins: A0A0G2K2P5, A0JNJ1, B1WAP7, G9CGD6, O14640, O75122, O88382, O95049, O97758, P34908, P39447, P51141, P54792, P70175, Q05AS8, Q07157, Q16825, Q5F488, Q5IS48, Q5SGD7, Q5TCQ9, Q5XI81, Q61062, Q62136, Q62728, Q62936, Q6DKE2, Q6P9H4, Q6ZM86, Q812E4, Q86UL8, Q8BMA3, Q8IVH8, Q8JHI3, Q8TDW5, Q920B0, Q924I2, Q925T6, Q92997, Q95168

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3233 predictions. Top by Δscore:

Variant	Effect	Δscore
X:38073572:T:A	acceptor_gain	1.0000
X:38073572:T:TA	acceptor_gain	1.0000
X:38073580:T:TA	acceptor_gain	1.0000
X:38073584:A:AG	acceptor_gain	1.0000
X:38073585:A:G	acceptor_gain	1.0000
X:38073696:GGG:G	donor_gain	1.0000
X:38073697:GGG:G	donor_gain	1.0000
X:38076697:GACAG:G	donor_gain	1.0000
X:38076698:ACAGG:A	donor_loss	1.0000
X:38076702:GT:G	donor_loss	1.0000
X:38076703:T:A	donor_loss	1.0000
X:38087027:A:G	donor_gain	1.0000
X:38089583:GTAGA:G	donor_gain	1.0000
X:38094282:A:AG	acceptor_gain	1.0000
X:38094288:T:TA	acceptor_gain	1.0000
X:38096125:A:AG	acceptor_gain	1.0000
X:38096126:C:G	acceptor_gain	1.0000
X:38096235:G:GC	donor_loss	1.0000
X:38096236:T:A	donor_loss	1.0000
X:38102336:TTTTA:T	acceptor_loss	1.0000
X:38102337:TTTAG:T	acceptor_loss	1.0000
X:38102338:TTAG:T	acceptor_loss	1.0000
X:38102339:TAGG:T	acceptor_loss	1.0000
X:38102340:A:C	acceptor_loss	1.0000
X:38102340:A:T	acceptor_loss	1.0000
X:38102341:G:A	acceptor_loss	1.0000
X:38102432:ACT:A	donor_gain	1.0000
X:38102435:G:GG	donor_gain	1.0000
X:38102457:TGGA:T	donor_gain	1.0000
X:38102460:A:T	donor_gain	1.0000

AlphaMissense

4802 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:38106717:T:A	V427D	1.000
X:38106727:C:G	C430W	1.000
X:38108605:T:A	V447D	1.000
X:38108609:G:C	K448N	1.000
X:38108609:G:T	K448N	1.000
X:38110370:T:A	V495D	1.000
X:38110372:T:A	W496R	1.000
X:38110372:T:C	W496R	1.000
X:38110408:G:A	G508R	1.000
X:38110408:G:C	G508R	1.000
X:38110408:G:T	G508W	1.000
X:38110409:G:A	G508E	1.000
X:38110409:G:T	G508V	1.000
X:38125435:T:C	L660P	1.000
X:38106659:G:C	G408R	0.999
X:38106660:G:A	G408D	0.999
X:38106660:G:T	G408V	0.999
X:38106705:T:C	L423P	0.999
X:38106735:T:A	L433Q	0.999
X:38106735:T:C	L433P	0.999
X:38108607:A:G	K448E	0.999
X:38108617:T:C	L451P	0.999
X:38108643:A:G	K460E	0.999
X:38108645:G:C	K460N	0.999
X:38108645:G:T	K460N	0.999
X:38108647:G:C	R461P	0.999
X:38108649:A:G	K462E	0.999
X:38108651:G:C	K462N	0.999
X:38108651:G:T	K462N	0.999
X:38108683:T:C	F473S	0.999

dbSNP variants (sampled 300 via entrez): RS1000034495 (X:38064472 T>C), RS1000035457 (X:37953619 C>A,T), RS1000047907 (X:38127169 G>A), RS1000055417 (X:37901757 G>A), RS1000058873 (X:38012825 C>T), RS1000072518 (X:38003696 T>A), RS1000090191 (X:38076132 A>G), RS1000103782 (X:37890103 G>A), RS1000112097 (X:37931438 TG>T), RS1000114870 (X:37889747 T>G), RS1000117100 (X:37945154 G>A), RS1000118113 (X:37906331 C>T), RS1000174001 (X:37906026 G>A), RS1000178348 (X:38021132 T>A), RS1000187353 (X:37961796 T>G)

Disease associations

OMIM: gene MIM:301126 | disease phenotypes: MIM:601086

GenCC curated gene-disease

Mondo (1): laterality defects, autosomal dominant (MONDO:0010991)

Orphanet (1): Visceral heterotaxy (Orphanet:450)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000824_10	Erectile dysfunction and prostate cancer treatment	9.000000e-06
GCST001961_4	Anorexia nervosa	1.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563391	Laterality Defects, Autosomal Dominant (supp.)

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
Estradiol	decreases expression, increases expression, increases reaction, affects binding, affects cotreatment	6
Valproic Acid	affects expression, decreases expression, increases expression	4
methylmercuric chloride	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tretinoin	increases expression	2
methyleugenol	decreases expression	1
trichostatin A	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Cadmium	increases expression	1
Carbamazepine	affects expression	1
Cosmetics	affects cotreatment, decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases expression	1
Flame Retardants	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Phthalic Acids	increases methylation	1

Clinical trials (associated diseases)

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