SNPH

Summary

SNPH (syntaphilin, HGNC:15931) is a protein-coding gene on chromosome 20p13, encoding Syntaphilin (O15079). Inhibits SNARE complex formation by absorbing free STX1A.

Syntaxin-1, synaptobrevin/VAMP, and SNAP25 interact to form the SNARE complex, which is required for synaptic vesicle docking and fusion. The protein encoded by this gene is membrane-associated and inhibits SNARE complex formation by binding free syntaxin-1. Expression of this gene appears to be brain-specific. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 9751 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_001318234

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15931
Approved symbol	SNPH
Name	syntaphilin
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	bA314N13.5
Ensembl gene	ENSG00000101298
Ensembl biotype	protein_coding
OMIM	604942
Entrez	9751

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000381867, ENST00000381873, ENST00000649598, ENST00000879304, ENST00000916147, ENST00000963823

RefSeq mRNA: 2 — MANE Select: NM_001318234 NM_001318234, NM_014723

CCDS: CCDS13012, CCDS82590

Canonical transcript exons

ENST00000381867 — 7 exons

Exon	Start	End
ENSE00001490085	1295776	1296421
ENSE00001490087	1294951	1294978
ENSE00001490089	1266294	1266397
ENSE00001693303	1300562	1300711
ENSE00001695411	1297145	1297252
ENSE00003524075	1266654	1266760
ENSE00003845863	1304878	1309327

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 97.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.6761 / max 191.1595, expressed in 1400 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183092	8.6761	1400

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
CA1 field of hippocampus	UBERON:0003881	97.60	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.22	gold quality
postcentral gyrus	UBERON:0002581	95.92	gold quality
orbitofrontal cortex	UBERON:0004167	95.91	gold quality
entorhinal cortex	UBERON:0002728	95.56	gold quality
superior frontal gyrus	UBERON:0002661	95.42	gold quality
parietal lobe	UBERON:0001872	95.39	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.98	gold quality
right frontal lobe	UBERON:0002810	94.87	gold quality
inferior olivary complex	UBERON:0002127	94.57	gold quality
cingulate cortex	UBERON:0003027	94.44	gold quality
anterior cingulate cortex	UBERON:0009835	94.41	gold quality
temporal lobe	UBERON:0001871	94.13	gold quality
frontal cortex	UBERON:0001870	94.06	gold quality
Ammon’s horn	UBERON:0001954	94.00	gold quality
primary visual cortex	UBERON:0002436	93.83	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.83	gold quality
amygdala	UBERON:0001876	93.61	gold quality
neocortex	UBERON:0001950	93.53	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.52	gold quality
cerebral cortex	UBERON:0000956	93.47	gold quality
prefrontal cortex	UBERON:0000451	93.38	gold quality
middle temporal gyrus	UBERON:0002771	93.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.35	gold quality
occipital lobe	UBERON:0002021	93.03	gold quality
nucleus accumbens	UBERON:0001882	92.74	gold quality
telencephalon	UBERON:0001893	92.73	gold quality
frontal pole	UBERON:0002795	92.44	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.36	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

158 targeting SNPH, 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-3120-5P	100.00	65.56	965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4492	99.87	68.25	3611

Literature-anchored findings (GeneRIF, showing 5)

• syntaphilin is an inhibitor of both SNARE-based fusion and dynamin-mediated endocytosis (PMID:12896979)
• Stressed mitochondria are removed from axons triggered by the bulk release of mitochondrial anchoring protein syntaphilin via a new class of mitochondria-derived cargos independent of Parkin, Drp1, and autophagy. (PMID:28472658)
• SNPH is a stress-regulated mitochondrial switch of the cell proliferation-motility balance in cancer, and its pathway may represent a therapeutic target. (PMID:28891816)
• By establishing the role of SNPH ubiquitination. (PMID:29898993)
• These data suggest that SNPH is a novel marker of high Gleason grade prostate cancer, differentially expressed at the invasive front compared with the central tumor bulk, and is potentially down-regulated in metastatic disease. (PMID:31079810)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	snphb	ENSDARG00000075539
danio_rerio	snpha	ENSDARG00000078485
mus_musculus	Snph	ENSMUSG00000027457
rattus_norvegicus	Snph	ENSRNOG00000009588

Paralogs (1): SYBU (ENSG00000147642)

Protein

Protein identifiers

Syntaphilin — O15079 (reviewed: O15079)

All UniProt accessions (2): O15079, A0A3B3IRY9

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits SNARE complex formation by absorbing free STX1A.

Subunit / interactions. Binds to STX1A. Interacts with DNM1; this interaction inhibits the binding of DNM1 to AMPH and DNM1-receptor-mediated endocytosis.

Subcellular location. Membrane. Synapse. Synaptosome.

Tissue specificity. Brain specific. Found in synapses.

Isoforms (2)

UniProt ID	Names	Canonical?
O15079-1	1	yes
O15079-2	2

RefSeq proteins (2): NP_001305163, NP_055538 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028197	Syntaphilin/Syntabulin	Family

Pfam: PF15290

UniProt features (15 total): modified residue 4, compositionally biased region 4, region of interest 3, chain 1, transmembrane region 1, splice variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15079-F1	61.80	0.24

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 (4): 200, 204, 214, 219

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 143 (showing top): MODULE_92, GCANCTGNY_MYOD_Q6, MODULE_563, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, CAGCTG_AP4_Q5, GGCNKCCATNK_UNKNOWN, EFC_Q6, GOBP_CELL_CELL_SIGNALING, GOBP_MEMBRANE_DOCKING, MODULE_66, GOBP_EXOCYTOSIS, GOBP_VESICLE_DOCKING_INVOLVED_IN_EXOCYTOSIS

GO Biological Process (3): neurotransmitter secretion (GO:0007269), obsolete synaptic vesicle docking (GO:0016081), neuron differentiation (GO:0030182)

GO Molecular Function (2): syntaxin-1 binding (GO:0017075), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytoplasmic microtubule (GO:0005881), membrane (GO:0016020), neuron projection (GO:0043005), presynapse (GO:0098793), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
neurotransmitter transport	1
chemical synaptic transmission	1
establishment of localization in cell	1
presynapse	1
signal release from synapse	1
cell differentiation	1
generation of neurons	1
syntaxin binding	1
binding	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
microtubule	1
plasma membrane bounded cell projection	1
synapse	1
cell junction	1

Protein interactions and networks

STRING

1050 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNPH	STX1A	Q16623	808
SNPH	TRAK1	Q9UPV9	748
SNPH	RHOT1	Q8IXI2	728
SNPH	KIF5B	P33176	715
SNPH	TRAK2	O60296	708
SNPH	DISC1	Q9NRI5	705
SNPH	SNAP25	P13795	695
SNPH	DYNLL1	P63167	687
SNPH	SYP	P08247	672
SNPH	BSN	Q9UPA5	668
SNPH	RHOT2	Q8IXI1	625
SNPH	ARMCX1	Q9P291	597
SNPH	MYO19	Q96H55	538
SNPH	MFN2	O95140	528
SNPH	MFN1	Q8IWA4	502

IntAct

20 interactions, top by confidence:

A	B	Type	Score
SNPH	ATP6V1H	psi-mi:“MI:0915”(physical association)	0.560
SNPH	RHBDD2	psi-mi:“MI:0915”(physical association)	0.560
SNPH	XPA	psi-mi:“MI:0915”(physical association)	0.560
ECE1	SNPH	psi-mi:“MI:0915”(physical association)	0.370
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
SYBU	SNPH	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
ATP6V1H	SNPH	psi-mi:“MI:0915”(physical association)	0.000
SNPH	RHBDD2	psi-mi:“MI:0915”(physical association)	0.000
XPA	SNPH	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): SNPH (Affinity Capture-MS), USP7 (Affinity Capture-Western), STUB1 (Affinity Capture-Western), KIF2A (Affinity Capture-Western), CLASP1 (Affinity Capture-Western), SNPH (Biochemical Activity), TUBB3 (Affinity Capture-Western), SNPH (Affinity Capture-RNA), SNPH (Two-hybrid), SNPH (Two-hybrid), XPA (Two-hybrid), SNPH (Affinity Capture-MS), SNPH (Biochemical Activity), SNPH (Affinity Capture-MS), SNPH (Affinity Capture-MS)

ESM2 similar proteins: A0A088MLT8, A2AQ25, B3KU38, B5DF41, E9PSK7, O15079, O35274, P0DPB3, P0DPB4, P12755, P49140, P85299, Q0D2I5, Q14DQ1, Q1LY51, Q3B7M3, Q3SYW5, Q4KMA0, Q4R3X1, Q50H33, Q5F3L9, Q5FVG6, Q5RD40, Q5XKK7, Q60698, Q6ZNC4, Q6ZUS6, Q6ZWB6, Q80U23, Q80U62, Q80XA6, Q812A5, Q86YI8, Q8BXL9, Q8K2W6, Q8ND83, Q8NFH8, Q8QFX1, Q8TEK3, Q924W7

Diamond homologs: B5DF41, O15079, Q80U23, Q8BHS8, Q9NX95

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1125 predictions. Top by Δscore:

Variant	Effect	Δscore
20:1266385:G:GT	donor_gain	0.9900
20:1266409:G:GT	donor_gain	0.9900
20:1266455:TCCA:T	donor_gain	0.9900
20:1266475:G:GT	donor_gain	0.9900
20:1266756:CTCAG:C	donor_loss	0.9900
20:1266757:TCAGG:T	donor_loss	0.9900
20:1266758:CAG:C	donor_loss	0.9900
20:1266759:AG:A	donor_loss	0.9900
20:1266760:GGTG:G	donor_loss	0.9900
20:1266761:GTGA:G	donor_loss	0.9900
20:1295897:G:GT	donor_gain	0.9900
20:1295898:G:T	donor_gain	0.9900
20:1297248:CCAAG:C	donor_loss	0.9900
20:1297249:CAAG:C	donor_loss	0.9900
20:1297250:AAGGT:A	donor_loss	0.9900
20:1297251:AGGT:A	donor_loss	0.9900
20:1297252:GGTAA:G	donor_loss	0.9900
20:1297253:G:GA	donor_loss	0.9900
20:1297254:T:A	donor_loss	0.9900
20:1300695:G:GT	donor_gain	0.9900
20:1300707:G:GT	donor_gain	0.9900
20:1300710:CGG:C	donor_loss	0.9900
20:1300711:GGT:G	donor_loss	0.9900
20:1300712:G:C	donor_loss	0.9900
20:1300712:G:GG	donor_gain	0.9900
20:1266459:GA:G	donor_gain	0.9800
20:1266462:TGCC:T	donor_gain	0.9800
20:1266463:GCCG:G	donor_gain	0.9800
20:1266474:GGGG:G	donor_gain	0.9800
20:1300539:T:TA	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000034905 (20:1281994 T>TG), RS1000045395 (20:1276214 C>T), RS1000064117 (20:1295271 G>A), RS1000259069 (20:1306724 GTGTC>G), RS1000323445 (20:1282905 G>A), RS1000371249 (20:1295013 C>A,T), RS1000381864 (20:1276687 T>C), RS1000476418 (20:1277118 C>T), RS1000518736 (20:1283941 C>G,T), RS1000530651 (20:1271007 A>C), RS1000591833 (20:1282461 G>A,T), RS1000669932 (20:1306465 T>A), RS1000711375 (20:1264524 T>G), RS1000714867 (20:1278353 C>T), RS1000776736 (20:1271327 A>G)

Disease associations

OMIM: gene MIM:604942 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002345_13	Response to cytadine analogues (cytosine arabinoside)	5.000000e-06
GCST008153_37	Lean body mass	7.000000e-06
GCST008158_120	Body mass index	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004995	lean body mass
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation, decreases methylation	2
Smoke	increases expression, decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
OTX015	increases expression	1
triphenyl phosphate	affects expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	affects methylation, increases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Methapyrilene	decreases methylation	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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