SNAP29

Summary

SNAP29 (synaptosome associated protein 29, HGNC:11133) is a protein-coding gene on chromosome 22q11.21, encoding Synaptosomal-associated protein 29 (O95721). SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. It is a selective cancer dependency (DepMap: 16.3% of cell lines).

This gene, a member of the SNAP25 gene family, encodes a protein involved in multiple membrane trafficking steps. Two other members of this gene family, SNAP23 and SNAP25, encode proteins that bind a syntaxin protein and mediate synaptic vesicle membrane docking and fusion to the plasma membrane. The protein encoded by this gene binds tightly to multiple syntaxins and is localized to intracellular membrane structures rather than to the plasma membrane. While the protein is mostly membrane-bound, a significant fraction of it is found free in the cytoplasm. Use of multiple polyadenylation sites has been noted for this gene.

Source: NCBI Gene 9342 — RefSeq curated summary.

At a glance

• Gene–disease (curated): CEDNIK syndrome (Strong, GenCC)
• Clinical variants (ClinVar): 355 total — 11 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 16.3% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_004782

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11133
Approved symbol	SNAP29
Name	synaptosome associated protein 29
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	SNAP-29, CEDNIK
Ensembl gene	ENSG00000099940
Ensembl biotype	protein_coding
OMIM	604202
Entrez	9342

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000215730, ENST00000439214, ENST00000490458, ENST00000880966, ENST00000880967, ENST00000880968, ENST00000880969, ENST00000938374

RefSeq mRNA: 1 — MANE Select: NM_004782 NM_004782

CCDS: CCDS13784

Canonical transcript exons

ENST00000215730 — 5 exons

Exon	Start	End
ENSE00000650957	20881049	20881134
ENSE00000650958	20883471	20883569
ENSE00001313354	20859007	20859347
ENSE00001315626	20887679	20891214
ENSE00003544794	20870337	20870533

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 94.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.6469 / max 207.1457, expressed in 1820 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191160	14.7431	1810
191158	8.4053	1782
191159	7.3543	1771
191157	1.1266	779
191163	0.0088	4
191162	0.0058	3
191161	0.0029	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	94.74	gold quality
right testis	UBERON:0004534	94.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.68	gold quality
testis	UBERON:0000473	93.03	gold quality
buccal mucosa cell	CL:0002336	92.05	gold quality
monocyte	CL:0000576	91.70	gold quality
mononuclear cell	CL:0000842	91.36	gold quality
leukocyte	CL:0000738	91.29	gold quality
adult organism	UBERON:0007023	91.20	gold quality
tendon of biceps brachii	UBERON:0008188	91.13	gold quality
lower esophagus mucosa	UBERON:0035834	91.07	gold quality
tongue squamous epithelium	UBERON:0006919	89.59	gold quality
islet of Langerhans	UBERON:0000006	89.52	gold quality
gastrocnemius	UBERON:0001388	89.32	gold quality
muscle of leg	UBERON:0001383	89.02	gold quality
stromal cell of endometrium	CL:0002255	89.01	gold quality
liver	UBERON:0002107	88.95	gold quality
skeletal muscle organ	UBERON:0014892	88.51	gold quality
muscle organ	UBERON:0001630	88.50	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.45	gold quality
granulocyte	CL:0000094	88.37	gold quality
heart right ventricle	UBERON:0002080	88.37	gold quality
right lobe of liver	UBERON:0001114	88.36	gold quality
type B pancreatic cell	CL:0000169	88.03	silver quality
smooth muscle tissue	UBERON:0001135	87.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.88	gold quality
right adrenal gland cortex	UBERON:0035827	87.81	gold quality
mucosa of transverse colon	UBERON:0004991	87.74	gold quality
cervix squamous epithelium	UBERON:0006922	87.73	gold quality
vastus lateralis	UBERON:0001379	87.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-31	no	1.90
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting SNAP29, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-605-3P	99.88	69.22	1833

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 16.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 19)

• SNAP-29 acts as a negative modulator for neurotransmitter release, probably by slowing recycling of the SNARE-based fusion machinery and synaptic vesicle turnover (PMID:15890653)
• a SNAP29 mutation codes for a SNARE protein involved in intracellular trafficking and causes a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma (PMID:15968592)
• SNAP29 mediated membrane fusion has an important role in endocytic recycling and consequently, in cell motility (PMID:20305790)
• a causal relationship between defective function of SNAP29 and the pleiotropic manifestations of CEDNIK syndrome (PMID:21073448)
• This work implicates SNAP29 as a major modifier of variable expressivity in 22q11.2 DS patients. (PMID:23231787)
• In mammalian cells, mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. (PMID:25419848)
• support a role of Snap29 at key steps of membrane trafficking, and predict that signaling defects may contribute to the pathogenesis of cerebral dysgenesis (PMID:25551675)
• phenotypic variability in Arab families with c.223delG mutation affected by cerebral dysgenesis, neuropathy, ichthyosis and keratoderma syndrome (PMID:25958742)
• Here, we identify a novel role for Snap29, an unconventional SNARE, in promoting kinetochore assembly during mitosis in Drosophila and human cells. Snap29 localizes to the outer kinetochore and prevents chromosome mis-segregation and the formation of cells with fragmented nuclei. (PMID:27647876)
• NEK3 kinase phosphorylates SNAP29 on its serine 105. NEK3-mediated phosphorylation determines membrane localization of SNAP29. Membrane-associated SNAP29 regulates Golgi and focal adhesion structures. (PMID:29454964)
• These findings suggest that down-regulation of OGT enhances cisplatin-induced autophagy via SNAP-29, resulting in cisplatin-resistant ovarian cancer. (PMID:30555541)
• autophagic degradation critically determines the production of HBV virions and HBsAg; this is controlled by the SNAP29-VAMP8 interaction (PMID:30742775)
• Silencing DAPK3 blocks the autophagosome-lysosome fusion by mediating SNAP29 in trophoblast cells under high glucose treatment. (PMID:31811899)
• Decoding three distinct states of the Syntaxin17 SNARE motif in mediating autophagosome-lysosome fusion. (PMID:32817423)
• Generation and Characterization of a CRISPR/Cas9-Mediated SNAP29 Knockout in Human Fibroblasts. (PMID:34069872)
• Alpha-Synuclein defects autophagy by impairing SNAP29-mediated autophagosome-lysosome fusion. (PMID:34535638)
• Snapshots from within the cell: Novel trafficking and non trafficking functions of Snap29 during tissue morphogenesis. (PMID:35256275)
• SNARE-binding protein synaptosomal-associated protein of 29 kDa (SNAP29) regulates the intracellular sequestration of glucose transporter 4 (GLUT4) vesicles in adipocytes. (PMID:36181414)
• Human YKT6 forms priming complex with STX17 and SNAP29 to facilitate autophagosome-lysosome fusion. (PMID:38340317)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	snap29	ENSDARG00000038518
mus_musculus	Snap29	ENSMUSG00000022765
rattus_norvegicus	Snap29	ENSRNOG00000001867
drosophila_melanogaster	Snap29	FBGN0034913
caenorhabditis_elegans		WBGENE00019305

Paralogs (3): SNAP23 (ENSG00000092531), SNAP25 (ENSG00000132639), SNAP47 (ENSG00000143740)

Protein

Protein identifiers

Synaptosomal-associated protein 29 — O95721 (reviewed: O95721)

Alternative names: Soluble 29 kDa NSF attachment protein, Vesicle-membrane fusion protein SNAP-29

All UniProt accessions (2): O95721, C9JAF7

UniProt curated annotations — full annotation on UniProt →

Function. SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. SNAP29 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Also plays a role in ciliogenesis by regulating membrane fusions.

Subunit / interactions. Forms a SNARE complex, composed of VAMP8, SNAP29 and STX17, involved in fusion of autophagosome with lysosome. Interacts with multiple syntaxins including STX6. Interacts with EIPR1. Interacts with STX17; this interaction is increased in the absence of TMEM39A. (Microbial infection) Interacts with Hantaan hantavirus nucleoprotein; this interaction prevents the breakdown of the viral glycoprotein N by virus-triggered autophagy. (Microbial infection) The interaction with STX17 is decreased in presence of SARS coronavirus-2/SARS-CoV-2 ORF3A protein.

Subcellular location. Cytoplasm. Golgi apparatus membrane. Cytoplasmic vesicle. Autophagosome membrane. Cell projection. Cilium membrane.

Tissue specificity. Found in brain, heart, kidney, liver, lung, placenta, skeletal muscle, spleen and pancreas.

Disease relevance. Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (CEDNIK) [MIM:609528] A neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis and palmoplantar keratoderma. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SNAP-25 family.

RefSeq proteins (1): NP_004773* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000727	T_SNARE_dom	Domain

UniProt features (18 total): modified residue 10, helix 2, region of interest 2, chain 1, domain 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4WY4	X-RAY DIFFRACTION	1.4
7BV6	X-RAY DIFFRACTION	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95721-F1	75.85	0.43

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 (10): 137, 163, 182, 185, 204, 210, 77, 78, 114, 130

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-6811438	Intra-Golgi traffic
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic

MSigDB gene sets: 293 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_VESICLE_LOCALIZATION, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOZGIT_ESR1_TARGETS_DN, GOBP_MEMBRANE_FUSION, GOBP_VESICLE_TARGETING, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_MACROAUTOPHAGY, GOBP_CELL_CELL_SIGNALING, GOBP_MEMBRANE_DOCKING, GOBP_EXOCYTOSIS

GO Biological Process (11): exocytosis (GO:0006887), obsolete vesicle targeting (GO:0006903), protein transport (GO:0015031), synaptic vesicle priming (GO:0016082), autophagosome membrane docking (GO:0016240), synaptic vesicle fusion to presynaptic active zone membrane (GO:0031629), cilium assembly (GO:0060271), membrane fusion (GO:0061025), autophagosome maturation (GO:0097352), autophagy (GO:0006914), cell projection organization (GO:0030030)

GO Molecular Function (3): SNAP receptor activity (GO:0005484), syntaxin binding (GO:0019905), protein binding (GO:0005515)

GO Cellular Component (18): Golgi membrane (GO:0000139), autophagosome membrane (GO:0000421), cytoplasm (GO:0005737), mitochondrion (GO:0005739), autophagosome (GO:0005776), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), ciliary pocket membrane (GO:0020018), SNARE complex (GO:0031201), azurophil granule membrane (GO:0035577), presynapse (GO:0098793), Golgi apparatus (GO:0005794), cilium (GO:0005929), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), ciliary membrane (GO:0060170)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Innate Immune System	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Immune System	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	5
vesicle fusion to plasma membrane	2
synaptic vesicle exocytosis	2
bounding membrane of organelle	2
intracellular membrane-bounded organelle	2
vesicle-mediated transport	1
secretion by cell	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein-containing complex assembly	1
exocytic process	1
autophagosome maturation	1
organelle localization by membrane tethering	1
synaptic vesicle membrane organization	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
membrane organization	1
macroautophagy	1
protein-containing complex disassembly	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cellular component organization	1
protein-macromolecule adaptor activity	1
membrane fusion	1
fusogenic activity	1
SNARE binding	1
binding	1
Golgi apparatus	1
vacuolar membrane	1
autophagosome	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNAP29	STX17	P56962	998
SNAP29	VAMP8	Q9BV40	998
SNAP29	VAMP7	P51809	996
SNAP29	ATG14	Q6ZNE5	993
SNAP29	STX7	O15400	991
SNAP29	EHD1	Q9H4M9	967
SNAP29	YKT6	O15498	966
SNAP29	STX3	Q13277	935
SNAP29	STX6	O43752	899
SNAP29	SNAP23	O00161	897
SNAP29	PLEKHM1	Q9Y4G2	888
SNAP29	STX8	Q9UNK0	860
SNAP29	STX4	Q12846	853
SNAP29	SNAP47	Q5SQN1	818
SNAP29	COG6	Q9Y2V7	795

IntAct

284 interactions, top by confidence:

A	B	Type	Score
SPC25	NDC80	psi-mi:“MI:0914”(association)	0.940
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
STX12	SNAP29	psi-mi:“MI:0915”(physical association)	0.880
SNAP29	STX12	psi-mi:“MI:0915”(physical association)	0.880
SNAP29	VAMP5	psi-mi:“MI:0915”(physical association)	0.830
SNAP29	VAMP8	psi-mi:“MI:0915”(physical association)	0.830
VAMP5	SNAP29	psi-mi:“MI:0915”(physical association)	0.830
STX17	SNAP29	psi-mi:“MI:0914”(association)	0.810
SNAP29	STX17	psi-mi:“MI:0915”(physical association)	0.810
SNAP29	STX17	psi-mi:“MI:0914”(association)	0.810
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
NAPA	SNAP23	psi-mi:“MI:0914”(association)	0.780
SNAP29	FAM9C	psi-mi:“MI:0915”(physical association)	0.740
SNAP29	STX3	psi-mi:“MI:0915”(physical association)	0.740
SNAP29	VAMP3	psi-mi:“MI:0915”(physical association)	0.740
SNAP29	TRAF3	psi-mi:“MI:0915”(physical association)	0.740
EXOC1	EXOC5	psi-mi:“MI:0914”(association)	0.730
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710

BioGRID (409): SNAP29 (Two-hybrid), SNAP29 (Two-hybrid), SNAP29 (Two-hybrid), VAMP5 (Two-hybrid), STX12 (Two-hybrid), FAM9B (Two-hybrid), SNAP29 (Affinity Capture-MS), TRPM7 (Affinity Capture-MS), VPS53 (Affinity Capture-MS), RNF20 (Affinity Capture-MS), C1orf122 (Affinity Capture-MS), MACF1 (Affinity Capture-MS), TRAF3 (Affinity Capture-MS), EXOC4 (Affinity Capture-MS), STX18 (Affinity Capture-MS)

ESM2 similar proteins: O00161, O09044, O15400, O35526, O64791, O70257, O70377, O70439, O88384, O95721, P32851, P36975, P36976, P36977, P36978, P58200, P61264, P61265, P61266, P61267, P61268, P83351, P83528, Q0E1I7, Q0II86, Q16623, Q16932, Q2KIU0, Q3ZBT5, Q42374, Q5NVG5, Q5R4L2, Q5R5K4, Q5R602, Q5TZ66, Q6PC54, Q7XIE2, Q8VZU2, Q944A9, Q9ERB0

Diamond homologs: O95721, Q0II86, Q5R5K4, Q6C5G0, Q9ERB0, Q9Z2P6, P83351

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NEK3	“up-regulates activity”	SNAP29	phosphorylation
SNAP29	“form complex”	“STX17-VAMP8 SNARE complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 144 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
Retrograde transport at the Trans-Golgi-Network	12	27.7×	4e-12
Intra-Golgi traffic	9	24.6×	2e-08
Insulin processing	5	24.0×	1e-04
COPII-mediated vesicle transport	8	13.7×	2e-05
trans-Golgi Network Vesicle Budding	5	13.4×	1e-03
Intra-Golgi and retrograde Golgi-to-ER traffic	9	9.9×	3e-05
COPI-mediated anterograde transport	8	9.2×	1e-04
ER to Golgi Anterograde Transport	6	8.4×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking	12	74.7×	4e-18
vesicle fusion	15	73.4×	1e-22
obsolete vesicle docking involved in exocytosis	5	27.4×	7e-05
intra-Golgi vesicle-mediated transport	5	21.4×	2e-04
Golgi to plasma membrane protein transport	5	21.4×	2e-04
endocytic recycling	9	19.6×	9e-08
exocytosis	14	17.3×	1e-11
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	6	16.4×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	8
Uncertain significance	164
Likely benign	116
Benign	31

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
2694564	NM_004782.4(SNAP29):c.235G>T (p.Glu79Ter)	Pathogenic
2712430	NM_004782.4(SNAP29):c.139C>T (p.Gln47Ter)	Pathogenic
2759269	NM_004782.4(SNAP29):c.466C>T (p.Gln156Ter)	Pathogenic
2759547	NM_004782.4(SNAP29):c.234del (p.Glu79fs)	Pathogenic
280840	NM_004782.4(SNAP29):c.85C>T (p.Arg29Ter)	Pathogenic
2863631	NM_004782.4(SNAP29):c.247_248del (p.Arg83fs)	Pathogenic
2867406	NM_004782.4(SNAP29):c.108del (p.Asp36fs)	Pathogenic
2871263	NM_004782.4(SNAP29):c.538dup (p.Ala180fs)	Pathogenic
50295	NM_004782.4(SNAP29):c.487dup (p.Ser163fs)	Pathogenic
620507	NM_004782.4(SNAP29):c.250C>T (p.Gln84Ter)	Pathogenic
872338	NM_004782.4(SNAP29):c.365_368del (p.Tyr122fs)	Pathogenic
1332801	NM_004782.4(SNAP29):c.118G>T (p.Asp40Tyr)	Likely pathogenic
2711082	NM_004782.4(SNAP29):c.238-1G>A	Likely pathogenic
2866500	NM_004782.4(SNAP29):c.520+2T>C	Likely pathogenic
3587851	NM_004782.4(SNAP29):c.265G>T (p.Glu89Ter)	Likely pathogenic
3587852	NM_004782.4(SNAP29):c.620-1G>C	Likely pathogenic
421595	NM_004782.4(SNAP29):c.622G>T (p.Glu208Ter)	Likely pathogenic
4849365	NM_004782.4(SNAP29):c.71_96dup (p.Asp33fs)	Likely pathogenic
987215	NM_004782.4(SNAP29):c.238-2A>G	Likely pathogenic

SpliceAI

621 predictions. Top by Δscore:

Variant	Effect	Δscore
22:20858565:GTTAC:G	donor_loss	1.0000
22:20858566:TTAC:T	donor_loss	1.0000
22:20858567:TAC:T	donor_loss	1.0000
22:20858568:ACC:A	donor_loss	1.0000
22:20858569:C:CA	donor_loss	1.0000
22:20858569:CCTT:C	donor_gain	1.0000
22:20870336:GGA:G	acceptor_gain	1.0000
22:20870530:ACAG:A	donor_gain	1.0000
22:20870531:CAGG:C	donor_loss	1.0000
22:20870534:G:C	donor_loss	1.0000
22:20870534:G:GG	donor_gain	1.0000
22:20881032:T:TA	acceptor_gain	1.0000
22:20881041:A:AG	acceptor_gain	1.0000
22:20881042:T:G	acceptor_gain	1.0000
22:20881046:A:G	acceptor_gain	1.0000
22:20883464:A:G	acceptor_gain	1.0000
22:20858568:A:AC	donor_gain	0.9900
22:20858569:C:CC	donor_gain	0.9900
22:20859252:G:GT	donor_gain	0.9900
22:20859345:GAGGT:G	donor_loss	0.9900
22:20859346:AG:A	donor_loss	0.9900
22:20859349:T:A	donor_loss	0.9900
22:20868185:A:G	donor_gain	0.9900
22:20870332:CCCA:C	acceptor_loss	0.9900
22:20870334:CA:C	acceptor_loss	0.9900
22:20870335:A:AC	acceptor_loss	0.9900
22:20870335:A:AG	acceptor_gain	0.9900
22:20870335:AG:A	acceptor_gain	0.9900
22:20870336:G:GT	acceptor_gain	0.9900
22:20870336:GG:G	acceptor_gain	0.9900

AlphaMissense

1708 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:20870412:A:C	S105R	0.997
22:20870414:C:A	S105R	0.997
22:20870414:C:G	S105R	0.997
22:20859318:T:C	S70P	0.995
22:20887706:T:C	L216P	0.994
22:20887718:C:A	A220D	0.994
22:20887769:T:C	L237P	0.994
22:20870434:T:A	I112N	0.991
22:20887717:G:C	A220P	0.990
22:20870341:T:C	L81P	0.989
22:20870445:T:C	F116L	0.989
22:20870447:T:A	F116L	0.989
22:20870447:T:G	F116L	0.989
22:20870443:T:A	V115E	0.988
22:20887703:G:C	R215P	0.986
22:20870439:A:C	S114R	0.985
22:20870441:C:A	S114R	0.985
22:20870441:C:G	S114R	0.985
22:20887832:T:C	L258P	0.985
22:20870350:A:C	Q84P	0.984
22:20870353:G:C	R85P	0.984
22:20870463:T:G	Y122D	0.984
22:20859141:T:C	F11L	0.983
22:20859143:C:A	F11L	0.983
22:20859143:C:G	F11L	0.983
22:20870413:G:T	S105I	0.983
22:20887685:T:C	L209P	0.983
22:20870351:G:C	Q84H	0.982
22:20870351:G:T	Q84H	0.982
22:20870392:T:A	M98K	0.982

dbSNP variants (sampled 300 via entrez): RS1000029728 (22:20878929 G>A), RS1000097751 (22:20880038 A>G), RS1000105352 (22:20866519 G>A,C), RS1000184690 (22:20865239 C>G), RS1000217317 (22:20874690 G>T), RS1000253905 (22:20858179 T>G), RS1000408198 (22:20890283 C>T), RS1000685750 (22:20889388 T>C), RS1000697763 (22:20883475 T>A), RS1000714285 (22:20858490 A>C,G), RS1000945487 (22:20868096 A>G), RS1001104682 (22:20862208 C>T), RS1001168918 (22:20866585 G>C), RS1001322585 (22:20861261 C>A,T), RS1001399432 (22:20867706 G>A,C,T)

Disease associations

OMIM: gene MIM:604202 | disease phenotypes: MIM:609528, MIM:608804

GenCC curated gene-disease

Disease	Classification	Inheritance
CEDNIK syndrome	Strong	Autosomal recessive

Mondo (2): CEDNIK syndrome (MONDO:0012290), hypomyelinating leukodystrophy 2 (MONDO:0012125)

Orphanet (3): CEDNIK syndrome (Orphanet:66631), Pelizaeus-Merzbacher-like disease (Orphanet:280270), Pelizaeus-Merzbacher-like disease due to GJC2 mutation (Orphanet:280282)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000100	Nephrotic syndrome
HP:0000135	Hypogonadism
HP:0000164	Abnormality of the dentition
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000268	Dolichocephaly
HP:0000276	Long face
HP:0000316	Hypertelorism
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000457	Depressed nasal ridge
HP:0000478	Abnormality of the eye
HP:0000494	Downslanted palpebral fissures
HP:0000496	Abnormality of eye movement
HP:0000504	Abnormality of vision
HP:0000648	Optic atrophy
HP:0000982	Palmoplantar keratoderma
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001271	Polyneuropathy
HP:0001273	Abnormal corpus callosum morphology
HP:0001284	Areflexia
HP:0001297	Stroke

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C537943	Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (supp.)
C563855	Leukodystrophy, Hypomyelinating, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066988 (SINGLE PROTEIN)

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
sodium arsenite	increases abundance, increases expression, affects binding, increases reaction	2
Valproic Acid	increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
cobaltous chloride	increases expression	1
lei gong teng	increases expression	1
epigallocatechin gallate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
quinocetone	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Fluorouracil	increases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Sodium Chloride	affects cotreatment, affects localization, decreases expression, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652493	Binding	Binding affinity to human SNAP29 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2GS	Abcam HeLa SNAP29 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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