SYPL2

Summary

SYPL2 (synaptophysin like 2, HGNC:27638) is a protein-coding gene on chromosome 1p13.3, encoding Synaptophysin-like protein 2 (Q5VXT5). Involved in communication between the T-tubular and junctional sarcoplasmic reticulum (SR) membranes.

Involved in substantia nigra development. Predicted to be located in membrane and synaptic vesicle. Predicted to be active in synaptic vesicle membrane.

Source: NCBI Gene 284612 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 38 total
• MANE Select transcript: NM_001040709

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27638
Approved symbol	SYPL2
Name	synaptophysin like 2
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Mg29
Ensembl gene	ENSG00000143028
Ensembl biotype	protein_coding
Entrez	284612

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000369872, ENST00000475497, ENST00000880157, ENST00000950144

RefSeq mRNA: 1 — MANE Select: NM_001040709 NM_001040709

CCDS: CCDS41365

Canonical transcript exons

ENST00000369872 — 6 exons

Exon	Start	End
ENSE00000957751	109475581	109475705
ENSE00000957752	109476776	109476977
ENSE00000957753	109477818	109478009
ENSE00000958195	109467059	109467133
ENSE00001451145	109479378	109482134
ENSE00001451146	109466546	109466897

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 98.73.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5276 / max 268.1286, expressed in 542 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4412	1.3987	464
4414	0.7414	127
4413	0.2866	61
4415	0.1008	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	98.73	gold quality
deltoid	UBERON:0001476	97.72	gold quality
gastrocnemius	UBERON:0001388	97.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.40	gold quality
quadriceps femoris	UBERON:0001377	96.98	gold quality
vastus lateralis	UBERON:0001379	96.71	gold quality
skeletal muscle tissue	UBERON:0001134	96.29	gold quality
biceps brachii	UBERON:0001507	96.14	gold quality
muscle of leg	UBERON:0001383	96.04	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.80	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.31	gold quality
muscle tissue	UBERON:0002385	92.26	gold quality
apex of heart	UBERON:0002098	87.41	gold quality
heart left ventricle	UBERON:0002084	86.51	gold quality
cardiac ventricle	UBERON:0002082	86.10	gold quality
body of tongue	UBERON:0011876	84.30	gold quality
right adrenal gland	UBERON:0001233	83.64	gold quality
left adrenal gland cortex	UBERON:0035825	83.43	gold quality
left adrenal gland	UBERON:0001234	83.37	gold quality
right adrenal gland cortex	UBERON:0035827	83.05	gold quality
metanephros cortex	UBERON:0010533	82.67	gold quality
adrenal cortex	UBERON:0001235	81.45	gold quality
right lobe of thyroid gland	UBERON:0001119	81.25	gold quality
adrenal gland	UBERON:0002369	81.04	gold quality
stromal cell of endometrium	CL:0002255	80.65	gold quality
heart	UBERON:0000948	80.53	gold quality
right lobe of liver	UBERON:0001114	80.17	gold quality
left lobe of thyroid gland	UBERON:0001120	80.14	gold quality
secondary oocyte	CL:0000655	79.61	gold quality
thyroid gland	UBERON:0002046	79.18	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.56

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Mitsugumin (MG)29 is expressed in astrocytes of Alzheimer disease brains associated with senile plaques, but is is not expressed in neurons around lesions. (PMID:22290180)
• SYPL2 is a susceptibility gene for morbid obesity. (PMID:25406998)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sypl2b	ENSDARG00000000690
danio_rerio	sypl2a	ENSDARG00000055307
mus_musculus	Sypl2	ENSMUSG00000027887
rattus_norvegicus	Sypl2	ENSRNOG00000019780
caenorhabditis_elegans		WBGENE00004979

Paralogs (3): SYPL1 (ENSG00000008282), SYP (ENSG00000102003), SYNPR (ENSG00000163630)

Protein

Protein identifiers

Synaptophysin-like protein 2 — Q5VXT5 (reviewed: Q5VXT5)

All UniProt accessions (2): Q5VXT5, B4DYR7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in communication between the T-tubular and junctional sarcoplasmic reticulum (SR) membranes.

Subcellular location. Membrane.

Similarity. Belongs to the synaptophysin/synaptobrevin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VXT5-1	1	yes
Q5VXT5-2	2

RefSeq proteins (1): NP_001035799* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001285	Synaptophysin/porin	Family
IPR008253	Marvel	Domain

Pfam: PF01284

UniProt features (15 total): topological domain 5, transmembrane region 4, chain 1, domain 1, region of interest 1, glycosylation site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VXT5-F1	81.24	0.47

Functional residue map

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

Glycosylation sites (1): 213

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 101 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_NEURAL_NUCLEUS_DEVELOPMENT, GOBP_SUBSTANTIA_NIGRA_DEVELOPMENT, GOBP_MIDBRAIN_DEVELOPMENT, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_HEAD_DEVELOPMENT, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_MEMBRANE_ORGANIZATION, GOBP_MUSCLE_CELL_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOCC_EXOCYTIC_VESICLE, GOCC_SECRETORY_VESICLE, GOBP_MUSCLE_CELL_DIFFERENTIATION

GO Biological Process (4): intracellular calcium ion homeostasis (GO:0006874), heart development (GO:0007507), substantia nigra development (GO:0021762), T-tubule organization (GO:0033292)

GO Molecular Function (0):

GO Cellular Component (3): synaptic vesicle membrane (GO:0030672), synaptic vesicle (GO:0008021), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
animal organ development	1
circulatory system development	1
midbrain development	1
neural nucleus development	1
plasma membrane organization	1
muscle cell development	1
membrane organization	1
synaptic vesicle	1
exocytic vesicle membrane	1
exocytic vesicle	1
presynapse	1
cellular anatomical structure	1

Protein interactions and networks

STRING

674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYPL2	JPH1	Q9HDC5	787
SYPL2	JPH2	Q9BR39	757
SYPL2	JPH4	Q96JJ6	752
SYPL2	JPH3	Q8WXH2	730
SYPL2	TRDN	Q13061	676
SYPL2	ASPH	Q12797	643
SYPL2	SRL	Q86TD4	619
SYPL2	CASQ1	P31415	608
SYPL2	RYR1	P21817	599
SYPL2	UNCX	A6NJT0	575
SYPL2	JSRP1	Q96MG2	529
SYPL2	PSMA5	P28066	522
SYPL2	PSRC1	Q6PGN9	520
SYPL2	KBTBD2	Q8IY47	507
SYPL2	MYBPHL	A2RUH7	491

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SYPL2	PCNA	psi-mi:“MI:0915”(physical association)	0.370
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
SYPL2	TSPAN15	psi-mi:“MI:0914”(association)	0.350
MFSD8	STXBP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): SYPL2 (Synthetic Lethality), TMEM192 (Affinity Capture-MS), TMEM120A (Affinity Capture-MS), MFSD12 (Affinity Capture-MS), REEP6 (Affinity Capture-MS), PVRL2 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), GCA (Affinity Capture-MS), TSPAN15 (Affinity Capture-MS), RTN2 (Affinity Capture-MS), VAMP3 (Affinity Capture-MS), SYNGR2 (Affinity Capture-MS), SYPL2 (Two-hybrid), SYPL2 (Two-hybrid), SYPL2 (Two-hybrid)

ESM2 similar proteins: A2VE13, A4K2N5, A4K2W1, B8BPI2, E1BY51, O09117, O09198, O35682, O62646, O88662, O89104, P21145, Q04941, Q10EJ2, Q16563, Q1RMQ3, Q28296, Q3URJ8, Q3ZBY0, Q5R6H1, Q5RAI2, Q5VXT5, Q64349, Q6DHB5, Q6GPN9, Q6P0C6, Q6P742, Q6VBQ5, Q6Y1E2, Q78S06, Q86TG1, Q86UW1, Q8BI08, Q8CJ61, Q8IZ96, Q8IZR5, Q8N2H4, Q8N8D7, Q91WN2, Q95MN6

Diamond homologs: O09117, O62646, O89104, P07825, P08247, P20488, P22831, Q16563, Q5VXT5, Q5YJC1, Q62277, Q8BGN8, Q8TBG9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1085 predictions. Top by Δscore:

Variant	Effect	Δscore
1:109467129:AGTGG:A	donor_loss	1.0000
1:109467130:GTGG:G	donor_gain	1.0000
1:109467132:GG:G	donor_gain	1.0000
1:109467133:GG:G	donor_gain	1.0000
1:109467133:GGTG:G	donor_loss	1.0000
1:109467134:G:GG	donor_gain	1.0000
1:109467134:GTGA:G	donor_loss	1.0000
1:109467135:T:A	donor_loss	1.0000
1:109475601:C:A	acceptor_gain	1.0000
1:109475602:G:A	acceptor_gain	1.0000
1:109476774:A:AG	acceptor_gain	1.0000
1:109476775:G:GG	acceptor_gain	1.0000
1:109476975:GTG:G	donor_gain	1.0000
1:109476975:GTGGT:G	donor_loss	1.0000
1:109476978:GT:G	donor_loss	1.0000
1:109476979:T:TG	donor_loss	1.0000
1:109476980:G:GG	donor_loss	1.0000
1:109478032:G:GT	donor_gain	1.0000
1:109475579:A:AG	acceptor_gain	0.9900
1:109475580:G:GG	acceptor_gain	0.9900
1:109476768:A:AG	acceptor_gain	0.9900
1:109476775:G:T	acceptor_loss	0.9900
1:109476775:GGTT:G	acceptor_gain	0.9900
1:109476973:TGGTG:T	donor_gain	0.9900
1:109476974:GGTGG:G	donor_gain	0.9900
1:109476978:G:GG	donor_gain	0.9900
1:109476981:A:AC	donor_loss	0.9900
1:109477510:G:T	donor_gain	0.9900
1:109477953:G:GT	donor_gain	0.9900
1:109467131:TGG:T	donor_gain	0.9800

AlphaMissense

1797 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:109475597:C:A	A49D	0.999
1:109475647:T:A	C66S	0.999
1:109475648:G:C	C66S	0.999
1:109475701:T:C	F84L	0.999
1:109475702:T:C	F84S	0.999
1:109475703:C:A	F84L	0.999
1:109475703:C:G	F84L	0.999
1:109476885:G:C	G122R	0.999
1:109476886:G:A	G122D	0.999
1:109477851:T:A	W164R	0.999
1:109477851:T:C	W164R	0.999
1:109477872:T:A	W171R	0.999
1:109477872:T:C	W171R	0.999
1:109477874:G:C	W171C	0.999
1:109477874:G:T	W171C	0.999
1:109477885:T:C	L175P	0.999
1:109477941:T:A	C194S	0.999
1:109477942:G:C	C194S	0.999
1:109477962:T:A	C201S	0.999
1:109477962:T:C	C201R	0.999
1:109477963:G:A	C201Y	0.999
1:109477963:G:C	C201S	0.999
1:109477964:C:G	C201W	0.999
1:109478005:C:A	S215Y	0.999
1:109478005:C:T	S215F	0.999
1:109479384:G:C	G219R	0.999
1:109479385:G:A	G219D	0.999
1:109479395:C:A	N222K	0.999
1:109479395:C:G	N222K	0.999
1:109479405:T:A	W226R	0.999

dbSNP variants (sampled 300 via entrez): RS1000187710 (1:109477892 T>C), RS1000404662 (1:109477947 G>A,T), RS1000604968 (1:109471706 C>A,T), RS1000683070 (1:109467393 C>T), RS1001003611 (1:109465976 C>G,T), RS1001352951 (1:109470776 T>C,G), RS1001357656 (1:109479993 A>G), RS1001409946 (1:109479627 C>T), RS1001613793 (1:109472865 C>T), RS1001984804 (1:109467409 G>C), RS1001995973 (1:109467045 C>T), RS1002053971 (1:109482208 T>C), RS1002244185 (1:109474431 G>A,T), RS1002354197 (1:109469296 A>G), RS1002361686 (1:109481669 T>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:145600

GenCC curated gene-disease

Mondo (1): malignant hyperthermia, susceptibility to, 1 (MONDO:0007783)

Orphanet (1): Malignant hyperthermia of anesthesia (Orphanet:423)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000578_1	Major depressive disorder	6.000000e-06
GCST000649_1	Chronic kidney disease	1.000000e-07
GCST003372_1	Glomerular filtration rate (creatinine)	5.000000e-08
GCST004292_29	Glomerular filtration rate (creatinine)	8.000000e-09
GCST005141_45	Cognitive ability (MTAG)	2.000000e-10
GCST005142_68	Cognitive ability	2.000000e-09
GCST007876_138	Estimated glomerular filtration rate	4.000000e-15
GCST008058_93	Estimated glomerular filtration rate	2.000000e-20
GCST008129_39	Body mass index	4.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0004340	body mass index

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535694	Malignant hyperthermia susceptibility type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Aldehydes	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Dexamethasone	increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases expression	1
Vincristine	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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