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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SEC22A
SEC22 homolog A, vesicle trafficking protein
Chromosome 3 · 3q21.1
NCBI Gene: 26984Ensembl: ENSG00000121542.13HGNC: HGNC:20260UniProt: Q96IW7
34PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingendoplasmic reticulum to Golgi vesicle-mediated transportSNAP receptor activityendoplasmic reticulum membraneobesitypolycystic ovary syndrometype 2 diabetes mellitusaortic disease
✦AI Summary

SEC22A is a vesicle trafficking protein functioning as a SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) involved in endoplasmic reticulum-to-Golgi transport. As a v-SNARE homolog of yeast Sec22p 1, SEC22A participates in membrane fusion machinery alongside other SNARE proteins including syntaxin 5, membrin, and rbet1 2. The protein localizes to the ER and interacts with regulatory proteins such as VAP-A, which binds promiscuously to multiple SNAREs including SEC22A (rsec22) 3. SEC22A is emerging as functionally significant beyond canonical trafficking. It associates with RAB18, a small GTPase implicated in membrane contact site regulation and cholesterol biosynthesis 4. Recent evidence indicates SEC22A mediates transport and localization of head-tail coupling apparatus proteins during spermatogenesis, with ARRDC5 affecting SEC22A-dependent positioning of NDC1 and SUN5 5. Therapeutically, enhancing SEC22A expression in neurons has been proposed as a strategy to prevent synucleinopathies like Parkinson's disease, as SEC22A suppresses α-synuclein toxicity 6. SEC22A's regulatory genomic context near ADCY5 in pancreatic islets suggests potential roles in glucose metabolism, though SEC22A expression itself appears independent of ADCY5-regulating enhancer variants 7.

Sources cited
1
SEC22A interacts with RAB18 and associates with membrane contact sites, microtubule/membrane-remodeling proteins, and lipid-modifying/transporting proteins in the context of cholesterol biosynthesis regulation
PMID: 37774976
2
SEC22B and its homologs SEC22A and SEC22C are SNARE proteins functioning in membrane fusion during ER-Golgi vesicle trafficking
PMID: 32748571
3
SEC22A-mediated transport is essential for proper localization of NDC1, SUN5, and head-tail coupling apparatus proteins during spermatogenesis
PMID: 37997706
4
SEC22A (human homolog of yeast Sec22p) suppresses α-synuclein and Bax toxicity, and enhancing its neuronal expression may prevent synucleinopathies like Parkinson's disease
PMID: 30579794
5
SEC22A is an adjacent gene to ADCY5 in pancreatic islets but its expression is not affected by ADCY5-regulating enhancer variants
PMID: 28684635
6
SEC22A is a mammalian homolog of yeast Sec22p, a v-SNARE protein required for ER-Golgi transport, and localizes to the ER
PMID: 9501016
7
VAP-A binds promiscuously to rsec22 (SEC22A) and other SNAREs, suggesting a general regulatory role in SNARE-mediated ER-Golgi vesicle trafficking
PMID: 11511104
8
rsec22b (SEC22 homolog) participates as a v-SNARE in ER-derived COPII-coated vesicles and forms complexes with syntaxin 5, membrin, and rbet1
PMID: 9647643
Disease Associationsⓘ20
obesityOpen Targets
0.35Weak
polycystic ovary syndromeOpen Targets
0.31Weak
type 2 diabetes mellitusOpen Targets
0.30Weak
aortic diseaseOpen Targets
0.28Weak
overnutritionOpen Targets
0.28Weak
diverticular diseaseOpen Targets
0.25Weak
Abruptio PlacentaeOpen Targets
0.16Weak
brain aneurysmOpen Targets
0.06Suggestive
placenta praeviaOpen Targets
0.05Suggestive
diabetes mellitusOpen Targets
0.04Suggestive
temporomandibular joint disorderOpen Targets
0.04Suggestive
cardiac arrestOpen Targets
0.03Suggestive
blood coagulation diseaseOpen Targets
0.02Suggestive
spinal stenosisOpen Targets
0.02Suggestive
infectionOpen Targets
0.00Suggestive
Alzheimer diseaseOpen Targets
0.00Suggestive
Parkinson diseaseOpen Targets
0.00Suggestive
synucleinopathyOpen Targets
0.00Suggestive
gastric cancerOpen Targets
0.00Suggestive
Testicular Germ Cell TumorOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GOLGA2Protein interaction100%STX5Protein interaction100%USO1Protein interaction100%GOSR1Protein interaction100%GOSR2Protein interaction100%BET1Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Liver
94%
Brain
92%
Ovary
91%
Lung
68%
Bone Marrow
43%
Gene Interaction Network
Click a node to explore
SEC22AGOLGA2STX5USO1GOSR1GOSR2BET1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96IW7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.73LoF Tolerant
pLIⓘ
0.33Tolerant
Observed/Expected LoF0.41 [0.24–0.73]
RankingsWhere SEC22A stands among ~20K protein-coding genes
  • #11,231of 20,598
    Most Researched34
  • #5,747of 17,882
    Most Constrained (LOEUF)0.73
Genes detectedSEC22A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Comparative proximity biotinylation implicates the small GTPase RAB18 in sterol mobilization and biosynthesis.
PMID: 37774976
J Biol Chem · 2023
1.00
2
The function of SEC22B and its role in human diseases.
PMID: 32748571
Cytoskeleton (Hoboken) · 2020
0.90
3
ARRDC5 deficiency impairs spermatogenesis by affecting SUN5 and NDC1.
PMID: 37997706
Development · 2023
0.80
4
Aegeline, a natural product from the plant Aegle marmelos, mimics the yeast SNARE protein Sec22p in suppressing α-synuclein and Bax toxicity in yeast.
PMID: 30579794
Bioorg Med Chem Lett · 2019
0.70
5
A Type 2 Diabetes-Associated Functional Regulatory Variant in a Pancreatic Islet Enhancer at the
PMID: 28684635
Diabetes · 2017
0.60