SNAPIN

Summary

SNAPIN (SNAP associated protein, HGNC:17145) is a protein-coding gene on chromosome 1q21.3, encoding SNARE-associated protein Snapin (O95295). Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. It is a selective cancer dependency (DepMap: 12.2% of cell lines).

The protein encoded by this gene is a coiled-coil-forming protein that associates with the SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) complex of proteins and the BLOC-1 (biogenesis of lysosome-related organelles) complex. Biochemical studies have identified additional binding partners. As part of the SNARE complex, it is required for vesicle docking and fusion and regulates neurotransmitter release. The BLOC-1 complex is required for the biogenesis of specialized organelles such as melanosomes and platelet dense granules. Mutations in gene products that form the BLOC-1 complex have been identified in mouse strains that are models of Hermansky-Pudlak syndrome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23557 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 22 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 42
• Cancer dependency (DepMap): dependent in 12.2% of screened cell lines
• MANE Select transcript: NM_012437

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17145
Approved symbol	SNAPIN
Name	SNAP associated protein
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	BLOC1S7, BORCS3
Ensembl gene	ENSG00000143553
Ensembl biotype	protein_coding
OMIM	607007
Entrez	23557

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000368685, ENST00000462880, ENST00000474959, ENST00000478558, ENST00000911963, ENST00000911964, ENST00000971969

RefSeq mRNA: 1 — MANE Select: NM_012437 NM_012437

CCDS: CCDS1049

Canonical transcript exons

ENST00000368685 — 4 exons

Exon	Start	End
ENSE00000960825	153659138	153659184
ENSE00001447750	153658703	153658886
ENSE00001809541	153661200	153661852
ENSE00003610107	153659448	153659566

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 98.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.5257 / max 133.6848, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5421	33.2224	1821
5420	0.8522	609
5422	0.4511	211

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.33	gold quality
left ventricle myocardium	UBERON:0006566	98.07	gold quality
secondary oocyte	CL:0000655	97.20	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.08	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.66	gold quality
myocardium	UBERON:0002349	96.44	gold quality
biceps brachii	UBERON:0001507	95.92	gold quality
tibialis anterior	UBERON:0001385	95.78	silver quality
apex of heart	UBERON:0002098	95.78	gold quality
quadriceps femoris	UBERON:0001377	95.75	gold quality
heart left ventricle	UBERON:0002084	95.72	gold quality
cardiac ventricle	UBERON:0002082	95.67	gold quality
right adrenal gland cortex	UBERON:0035827	95.59	gold quality
right adrenal gland	UBERON:0001233	95.55	gold quality
vastus lateralis	UBERON:0001379	95.55	gold quality
heart right ventricle	UBERON:0002080	95.53	gold quality
gastrocnemius	UBERON:0001388	95.50	gold quality
muscle of leg	UBERON:0001383	95.35	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.28	gold quality
deltoid	UBERON:0001476	95.23	gold quality
heart	UBERON:0000948	95.01	gold quality
left adrenal gland	UBERON:0001234	94.96	gold quality
left adrenal gland cortex	UBERON:0035825	94.82	gold quality
right coronary artery	UBERON:0001625	94.69	gold quality
cardiac atrium	UBERON:0002081	94.65	gold quality
right atrium auricular region	UBERON:0006631	94.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.61	gold quality
muscle tissue	UBERON:0002385	94.56	gold quality
skeletal muscle tissue	UBERON:0001134	94.53	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.40	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.79
E-CURD-112	no	2.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting SNAPIN, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4803	99.98	71.99	3117
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-95-5P	99.89	72.17	3973
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-3064-5P	99.26	66.13	1497

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 19)

• results suggest that RGS7 could play a role in synaptic vesicle exocytosis through its interaction with snapin (PMID:12659861)
• EBAG9 and Snapin have roles in controlling exocytosis processes (PMID:15635093)
• results demonstrate that snapin is a binding partner of dysbindin-1 in vitro and in the brain; both dysbindin-1 and snapin are concentrated in tissue enriched in synaptic vesicle membranes and less commonly in postsynaptic densities (PMID:16980328)
• Snapin links the alpha(1A)-AR to TRPC6, augmenting Ca(2+) influx via ROC channels (PMID:17684020)
• Data describe for the first time the expression of SNAPIN in germ cells which raises possibility that SNAPIN plays an extra role in mammals which is germ cell specific. (PMID:19168546)
• Snapin plays an important role as a linker between the water channel and the t-SNARE complex, leading to the fusion event, and the pairing with specific t-SNAREs is essential for the specificity of membrane recognition and fusion. (PMID:19515809)
• PKA-dependent phosphorylation of snapin increases interaction among insulin secretory vesicle-associated proteins, thereby potentiating glucose-stimulated insulin secretion. (PMID:21356520)
• These results suggest that Snapin may play a key role in regulating the cellular localization of human cytomegalovirus UL70, leading to modulation of viral DNA synthesis and progeny production. (PMID:21917956)
• These observations identify Snapin as a novel endogenous TLR2 ligand in rheumatoid arthritis, and thus support a role for persistent TLR2 signalling in pathogenesis. (PMID:22523426)
• Our findings reveal that Atg14L, previously considered to be solely a Beclin 1-binding autophagy protein, plays a novel role in the late stage of endocytic trafficking in conjunction with Snapin (PMID:22797916)
• Snapin, a SNAP-25 (synaptosomal-associated protein-25) interacting protein, interacts with LRRK2. (PMID:23949442)
• Authors propose that Snapin connects chlamydial inclusions with the microtubule network by interacting with both Chlamydia psittaci IncB and dynein. (PMID:24751478)
• Disruption of Snapin-PKR2 interaction did not affect PKR2 signaling, but increased the ligand-induced degradation, implying a role of Snapin in the trafficking of PKR2. (PMID:26687946)
• Taken together, these results suggest that Snapin, the pUL130 interacting protein, has a role in modulating HCMV DNA synthesis. (PMID:27240978)
• These results provide the evidence of a direct regulatory role of Snapin on Cav1.3 channels in atrial myocytes. (PMID:27915047)
• These observations suggest an important role for SNAPIN and autophagy in the homeostasis of macrophages, particularly long-lived tissue resident macrophages. (PMID:27929705)
• Inhibition of Snapin enhanced localization of HIV-1 with TLR8(+) early endosomes, triggered a pro-inflammatory response, and inhibited trans-infection of CD4(+) T cells. (PMID:28923824)
• SNAPIN Regulates Cell Cycle Progression to Promote Pancreatic beta Cell Growth. (PMID:34194388)
• Snapin Specifically Up-Regulates Cav1.3 Ca(2+) Channel Variant with a Long Carboxyl Terminus. (PMID:34681928)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	snapin	ENSDARG00000062382
mus_musculus	Snapin	ENSMUSG00000001018
rattus_norvegicus	Snapin	ENSRNOG00000013356
drosophila_melanogaster	Snapin	FBGN0031455
caenorhabditis_elegans		WBGENE00015327

Protein

Protein identifiers

SNARE-associated protein Snapin — O95295 (reviewed: O95295)

Alternative names: Biogenesis of lysosome-related organelles complex 1 subunit 7, Synaptosomal-associated protein 25-binding protein

All UniProt accessions (1): O95295

UniProt curated annotations — full annotation on UniProt →

Function. Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking and synaptic vesicle recycling. May modulate a step between vesicle priming, fusion and calcium-dependent neurotransmitter release through its ability to potentiate the interaction of synaptotagmin with the SNAREs and the plasma-membrane-associated protein SNAP25. Its phosphorylation state influences exocytotic protein interactions and may regulate synaptic vesicle exocytosis. May also have a role in the mechanisms of SNARE-mediated membrane fusion in non-neuronal cells. As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor.

Subunit / interactions. Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos. Component of the BLOC-one-related complex (BORC) which is composed of BLOC1S1, BLOC1S2, BORCS5, BORCS6, BORCS7, BORCS8, KXD1 and SNAPIN. Associates with the SNARE complex. Interacts with CSNK1D, SNAP23 and STX4A but not with STX1A, VAMP2 and SYT1. Interacts with SNAP25; the interaction with SNAP25 is increased by its phosphorylation. Interacts with CNTRL, NANOS1, PUM2 and RGS7. Interacts with TOR1A; the interaction is direct and associates SNAPIN with the CSN complex. (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL70.

Subcellular location. Membrane. Cytoplasm. Cytosol. Perinuclear region. Golgi apparatus membrane. Lysosome membrane. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane.

Tissue specificity. Expressed in male germ cells of adult testis (at protein level).

Post-translational modifications. Phosphorylated by CSNK1D/CK1. Phosphorylated by PKD, phosphorylation controls SNAPIN protein stability.

Similarity. Belongs to the SNAPIN family.

RefSeq proteins (1): NP_036569* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017246	Snapin	Family
IPR028119	Snapin/Pallidin/Snn1	Family

Pfam: PF14712

UniProt features (12 total): modified residue 7, initiator methionine 1, chain 1, sequence variant 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95295-F1	87.42	0.69

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 (7): 133, 2, 10, 14, 50, 126, 129

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-199991	Membrane Trafficking
R-HSA-199992	trans-Golgi Network Vesicle Budding
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 216 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_LYSOSOMAL_TRANSPORT, GOBP_VACUOLE_ORGANIZATION, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_SYNAPTIC_VESICLE_CYTOSKELETAL_TRANSPORT, GOBP_INSULIN_SECRETION, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_MEMBRANE_FUSION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (30): intracellular protein transport (GO:0006886), lysosome organization (GO:0007040), lysosomal lumen acidification (GO:0007042), neurotransmitter secretion (GO:0007269), anterograde axonal transport (GO:0008089), retrograde axonal transport (GO:0008090), endosome to lysosome transport (GO:0008333), negative regulation of neuron projection development (GO:0010977), synaptic vesicle exocytosis (GO:0016079), synaptic vesicle maturation (GO:0016188), neuron projection development (GO:0031175), protein-containing complex localization (GO:0031503), synaptic vesicle fusion to presynaptic active zone membrane (GO:0031629), lysosome localization (GO:0032418), melanosome organization (GO:0032438), synaptic vesicle transport (GO:0048489), anterograde synaptic vesicle transport (GO:0048490), regulation of endosome size (GO:0051036), protein maturation (GO:0051604), regulation of lysosome size (GO:0062196), neuron cellular homeostasis (GO:0070050), organelle transport along microtubule (GO:0072384), terminal button organization (GO:0072553), autophagosome maturation (GO:0097352), late endosome to lysosome transport (GO:1902774), positive regulation of late endosome to lysosome transport (GO:1902824), regulation of synaptic vesicle exocytosis (GO:2000300), exocytosis (GO:0006887), chemical synaptic transmission (GO:0007268), establishment of vesicle localization (GO:0051650)

GO Molecular Function (2): SNARE binding (GO:0000149), protein binding (GO:0005515)

GO Cellular Component (20): Golgi membrane (GO:0000139), acrosomal vesicle (GO:0001669), manchette (GO:0002177), cytosol (GO:0005829), synaptic vesicle (GO:0008021), secretory granule (GO:0030141), synaptic vesicle membrane (GO:0030672), BLOC-1 complex (GO:0031083), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), cytoplasmic side of lysosomal membrane (GO:0098574), BORC complex (GO:0099078), axon cytoplasm (GO:1904115), microvesicle (GO:1990742), cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
presynapse	3
establishment of localization in cell	2
signal release from synapse	2
axonal transport	2
axon cytoplasm	2
endomembrane system	2
intracellular protein localization	1
protein transport	1
intracellular transport	1
lytic vacuole organization	1
vacuolar acidification	1
neurotransmitter transport	1
chemical synaptic transmission	1
lysosomal transport	1
intercellular transport	1
vesicle-mediated transport	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
neurotransmitter secretion	1
regulated exocytosis	1
vesicle-mediated transport in synapse	1
synaptic vesicle cycle	1
vesicle organization	1
developmental maturation	1
neuron development	1
plasma membrane bounded cell projection organization	1
macromolecule localization	1
synaptic vesicle exocytosis	1
synaptic vesicle membrane organization	1
vesicle fusion to plasma membrane	1
vacuolar localization	1
pigment granule organization	1
transport	1
cellular process	1
establishment of vesicle localization	1
synaptic vesicle localization	1
anterograde axonal transport	1

Protein interactions and networks

STRING

1456 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNAPIN	BLOC1S1	P78537	999
SNAPIN	BLOC1S3	Q6QNY0	999
SNAPIN	BLOC1S2	Q6QNY1	999
SNAPIN	BLOC1S6	Q9UL45	999
SNAPIN	DTNBP1	Q96EV8	998
SNAPIN	SNAP25	P13795	992
SNAPIN	BORCS6	Q96GS4	990
SNAPIN	KXD1	Q9BQD3	988
SNAPIN	BORCS7	Q96B45	984
SNAPIN	BORCS5	Q969J3	983
SNAPIN	BORCS8	Q96FH0	956
SNAPIN	BLOC1S5	Q8TDH9	924
SNAPIN	SNAP23	O00161	917
SNAPIN	ATG14	Q6ZNE5	900
SNAPIN	VAMP2	P19065	794

IntAct

333 interactions, top by confidence:

A	B	Type	Score
SNAPIN	DTNBP1	psi-mi:“MI:0915”(physical association)	0.900
DTNBP1	SNAPIN	psi-mi:“MI:0915”(physical association)	0.900
DTNBP1	SNAPIN	psi-mi:“MI:0914”(association)	0.900
SNAPIN	BLOC1S2	psi-mi:“MI:0915”(physical association)	0.830
BLOC1S2	SNAPIN	psi-mi:“MI:0915”(physical association)	0.830
BLOC1S2	SNAPIN	psi-mi:“MI:0914”(association)	0.830
SNAPIN	BLOC1S1	psi-mi:“MI:0915”(physical association)	0.810
IKBIP	SNAPIN	psi-mi:“MI:0914”(association)	0.670
ENTHD1	SNAPIN	psi-mi:“MI:0915”(physical association)	0.670
SNAPIN	KRT27	psi-mi:“MI:0915”(physical association)	0.670
FSD2	SNAPIN	psi-mi:“MI:0915”(physical association)	0.670
SNAPIN	INSYN1	psi-mi:“MI:0915”(physical association)	0.670
SNAPIN	ENTHD1	psi-mi:“MI:0915”(physical association)	0.670
SNAPIN	IKBIP	psi-mi:“MI:0915”(physical association)	0.670
CEP170P1	SNAPIN	psi-mi:“MI:0915”(physical association)	0.670
BLOC1S6	SNAPIN	psi-mi:“MI:0914”(association)	0.640
COG7	ILVBL	psi-mi:“MI:0914”(association)	0.640
SNAPIN	Slc14a2	psi-mi:“MI:0407”(direct interaction)	0.620
SNAPIN	Slc14a2	psi-mi:“MI:0915”(physical association)	0.620
SNAPIN	Slc14a2	psi-mi:“MI:0403”(colocalization)	0.620
SNAPIN	SLC14A2	psi-mi:“MI:0915”(physical association)	0.600
SNAPIN	SLC14A2	psi-mi:“MI:0407”(direct interaction)	0.600

BioGRID (242): SNAPIN (Affinity Capture-MS), SNAPIN (Affinity Capture-MS), SNAPIN (Affinity Capture-MS), SNAPIN (Affinity Capture-MS), SNAPIN (Affinity Capture-MS), SNAPIN (Affinity Capture-MS), SNAPIN (Affinity Capture-MS), BLOC1S2 (Co-fractionation), SNAPIN (Co-fractionation), SNAPIN (Affinity Capture-MS), SNAPIN (Proximity Label-MS), SNAPIN (Affinity Capture-MS), SNAPIN (Affinity Capture-MS), SNAPIN (Affinity Capture-MS), SNAPIN (Affinity Capture-MS)

ESM2 similar proteins: A1Z9S1, A2XK00, A7RZS0, B4FGS2, B8B624, F4K657, G0RY74, O22929, O80877, O95295, P60192, Q0V9C8, Q0VIA1, Q13503, Q16RX1, Q17MI0, Q22616, Q2TBU8, Q3SZV2, Q3ZCF2, Q4R6N3, Q4R6W4, Q50HP4, Q5FWT9, Q5R6P5, Q5RE46, Q6ASS9, Q6CGR3, Q6DBR9, Q6DDT0, Q6DJ25, Q6IP67, Q7PR68, Q7PTL0, Q7XAM0, Q7ZTI5, Q8LDS5, Q94JY4, Q95XD3, Q9BRV8

Diamond homologs: O95295, P60192, Q9VQF9, Q9Z266

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
LRRK2	down-regulates	SNAPIN	phosphorylation
TOR1A	“up-regulates activity”	SNAPIN	binding
SNAPIN	“up-regulates activity”	SNAP25	binding
SNAPIN	“form complex”	BLOC-1	binding
PRKACA	“up-regulates activity”	SNAPIN	phosphorylation
RNF13	“up-regulates activity”	SNAPIN	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
trans-Golgi Network Vesicle Budding	7	26.5×	2e-06
Golgi Associated Vesicle Biogenesis	7	20.9×	6e-06
Retrograde transport at the Trans-Golgi-Network	5	16.4×	8e-04
Signaling by ALK fusions and activated point mutants	5	11.2×	4e-03
Formation of the cornified envelope	7	9.2×	8e-04
Keratinization	7	5.8×	5e-03
Membrane Trafficking	9	5.0×	4e-03
Vesicle-mediated transport	9	4.7×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
anterograde synaptic vesicle transport	7	73.8×	1e-09
melanosome organization	7	48.3×	2e-08
anterograde axonal transport	7	43.3×	3e-08
platelet dense granule organization	5	35.9×	2e-05
morphogenesis of an epithelium	7	25.6×	1e-06
intermediate filament organization	9	23.1×	3e-08
epithelial cell differentiation	6	11.2×	7e-04
neuron projection development	7	9.1×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
4075380	NM_012437.6(SNAPIN):c.91G>T (p.Glu31Ter)	Pathogenic
4075381	NM_012437.6(SNAPIN):c.144-1G>A	Pathogenic
4075382	NM_012437.6(SNAPIN):c.112C>T (p.Gln38Ter)	Pathogenic
402168	NM_012437.6(SNAPIN):c.163C>T (p.Arg55Trp)	Likely pathogenic
4075383	NM_012437.6(SNAPIN):c.147G>C (p.Glu49Asp)	Likely pathogenic

SpliceAI

652 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153658873:G:GG	donor_gain	1.0000
1:153658899:G:GT	donor_gain	1.0000
1:153658899:G:T	donor_gain	1.0000
1:153659444:CCAGA:C	acceptor_loss	1.0000
1:153659445:CAGA:C	acceptor_loss	1.0000
1:153659446:AGA:A	acceptor_loss	1.0000
1:153659447:GAACT:G	acceptor_gain	1.0000
1:153659564:CAG:C	donor_loss	1.0000
1:153659565:AGGTA:A	donor_loss	1.0000
1:153659566:GG:G	donor_loss	1.0000
1:153662552:AAGAT:A	acceptor_gain	1.0000
1:153662553:AGAT:A	acceptor_gain	1.0000
1:153662554:GAT:G	acceptor_gain	1.0000
1:153662555:AT:A	acceptor_gain	1.0000
1:153662555:ATC:A	acceptor_loss	1.0000
1:153662557:C:CC	acceptor_gain	1.0000
1:153662703:A:AC	donor_gain	1.0000
1:153662704:C:CC	donor_gain	1.0000
1:153662704:CAG:C	donor_gain	1.0000
1:153662719:T:A	donor_gain	1.0000
1:153663209:CTGTA:C	donor_loss	1.0000
1:153663210:TGTAC:T	donor_loss	1.0000
1:153663211:GTA:G	donor_loss	1.0000
1:153663212:TACCT:T	donor_loss	1.0000
1:153663213:ACCTG:A	donor_loss	1.0000
1:153663214:C:A	donor_loss	1.0000
1:153663272:TGGCC:T	acceptor_gain	1.0000
1:153663274:GCCCT:G	acceptor_loss	1.0000
1:153663275:CC:C	acceptor_gain	1.0000
1:153663275:CCCTG:C	acceptor_loss	1.0000

AlphaMissense

859 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153659155:T:C	L54P	1.000
1:153659176:T:C	L61P	1.000
1:153659511:T:C	L85P	1.000
1:153659519:G:C	A88P	1.000
1:153659520:C:A	A88D	1.000
1:153659532:T:A	V92D	1.000
1:153659553:T:C	L99P	1.000
1:153659562:C:A	A102D	1.000
1:153661207:T:C	L106P	1.000
1:153659155:T:A	L54H	0.999
1:153659158:G:C	R55P	0.999
1:153659178:G:C	A62P	0.999
1:153659451:T:C	L65P	0.999
1:153659502:T:A	V82D	0.999
1:153659511:T:A	L85Q	0.999
1:153659514:T:C	L86P	0.999
1:153659526:G:C	R90P	0.999
1:153659528:C:A	R91S	0.999
1:153659529:G:C	R91P	0.999
1:153659541:T:A	V95D	0.999
1:153659545:C:A	N96K	0.999
1:153659545:C:G	N96K	0.999
1:153659548:C:A	N97K	0.999
1:153659548:C:G	N97K	0.999
1:153659550:T:A	I98N	0.999
1:153659550:T:C	I98T	0.999
1:153659553:T:A	L99Q	0.999
1:153659561:G:C	A102P	0.999
1:153661216:T:C	L109P	0.999
1:153658862:T:C	L40P	0.998

dbSNP variants (sampled 300 via entrez): RS1000044810 (1:153660446 G>C), RS1000402483 (1:153656934 C>T), RS1001074206 (1:153661399 TCA>T), RS1001203403 (1:153661358 A>G), RS1001265820 (1:153660391 G>A), RS1001338250 (1:153661628 T>A,C,G), RS1001810004 (1:153660161 T>TG), RS1003288292 (1:153657376 T>A), RS1003320919 (1:153657657 G>A), RS1003393430 (1:153657211 C>T), RS1004215906 (1:153656890 T>C), RS1004547854 (1:153658413 T>G), RS1004640867 (1:153657934 C>A,T), RS1006309601 (1:153659838 C>T), RS1007053265 (1:153658893 G>A,T)

Disease associations

OMIM: gene MIM:607007 | disease phenotypes: MIM:621393

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities (MONDO:0980710)

Orphanet (0):

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000175	Cleft palate
HP:0000347	Micrognathia
HP:0000518	Cataract
HP:0000568	Microphthalmia
HP:0000648	Optic atrophy
HP:0001188	Hand clenching
HP:0001274	Agenesis of corpus callosum
HP:0001298	Encephalopathy
HP:0001321	Cerebellar hypoplasia
HP:0001339	Lissencephaly
HP:0001371	Flexion contracture
HP:0001511	Intrauterine growth retardation
HP:0001558	Decreased fetal movement
HP:0001629	Ventricular septal defect
HP:0001762	Talipes equinovarus
HP:0001789	Hydrops fetalis
HP:0001883	Talipes
HP:0002119	Ventriculomegaly
HP:0002126	Polymicrogyria
HP:0002188	Delayed CNS myelination
HP:0002283	Global brain atrophy
HP:0002508	Brainstem dysplasia
HP:0002518	Abnormal periventricular white matter morphology
HP:0002539	Cortical dysplasia
HP:0006855	Cerebellar vermis atrophy
HP:0006956	Lateral ventricle dilatation
HP:0007165	Periventricular heterotopia
HP:0009879	Simplified gyral pattern
HP:0010557	Overlapping fingers

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects expression, affects response to substance	1
Methylcholanthrene	affects binding, increases reaction	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Thiram	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Palmitic Acid	increases phosphorylation	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2GT	Abcam HeLa SNAPIN KO	Cancer cell line	Female
CVCL_KU04	HeLa SilenciX SNAPIN	Cancer cell line	Female

Clinical trials (associated diseases)

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