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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SCFD1
sec1 family domain containing 1
Chromosome 14 · 14q12
NCBI Gene: 23256Ensembl: ENSG00000092108.22HGNC: HGNC:20726UniProt: A0A7I2V590
120PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cis-Golgi networkregulation of protein transportprotein bindingnegative regulation of autophagosome assemblyneurodegenerative diseasebronchial diseaseamyotrophic lateral sclerosisplacental retention
✦AI Summary

SCFD1 is a Sec1 family protein that plays a critical role in intracellular vesicular transport, particularly in SNARE-pin assembly and ER-Golgi trafficking 1. It functions as a Sec1/Munc18-like regulatory protein that interacts with syntaxin 5 and the COG membrane tethering complex to mediate both anterograde ER-to-Golgi and retrograde Golgi-to-ER transport 1. SCFD1 is involved in post-Golgi vesicle-mediated transport and regulation of autophagosome assembly through its protein-binding interactions. Clinically, SCFD1 has emerged as a candidate therapeutic target for multiple neurodegenerative conditions. Genome-wide association studies identified SCFD1 as a risk locus for amyotrophic lateral sclerosis (ALS) 2, with proteome-wide association studies confirming its causal relationship with ALS risk 34. Additionally, integrative multi-omics analysis designated SCFD1 as a high-confidence therapeutic target for glioblastoma 5. In cancer biology, SCFD1 was upregulated in PD-1+ colon cancer cells treated with nivolumab, suggesting involvement in anti-PD-1 immunotherapy responses 6. While SCFD1 showed associations with skeletal muscle aging in neural network analyses 7, subsequent targeted validation failed to confirm its differential expression in aged muscle. These findings indicate SCFD1's multifaceted roles in neurodegeneration and cancer biology, warranting further functional validation.

Sources cited
1
SCFD1 (Scfd1/Sly1p) mediates ER-Golgi anterograde and retrograde trafficking through interaction with syntaxin 5, COG, and other membrane tethering complexes
PMID: 31357511
2
SCFD1 identified as a new risk locus associated with amyotrophic lateral sclerosis through genome-wide association study
PMID: 27455348
3
SCFD1 identified as a high-confidence therapeutic target for glioblastoma through integrative proteome-wide and transcriptome-wide association studies with Mendelian randomization
PMID: 40638267
4
SCFD1 in brain identified as a candidate drug target for amyotrophic lateral sclerosis through Mendelian randomization analysis of proteomic data
PMID: 36759259
5
SCFD1 identified as an ALS risk gene through proteome-wide association study using brain protein quantitative trait loci and GWAS data
PMID: 37639066
6
SCFD1 upregulated in nivolumab-treated PD-1+ human colon cancer cells
PMID: 35246475
7
SCFD1 identified as a main interacting gene associated with long-term exercise in older adults through artificial neural network inference analysis, though differential expression was not confirmed by RT-qPCR
PMID: 39210538
8
SCFD1 rs10139154 polymorphism showed no association with ALS risk in a case-control study
PMID: 35234271
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.53Moderate
bronchial diseaseOpen Targets
0.30Weak
amyotrophic lateral sclerosisOpen Targets
0.28Weak
placental retentionOpen Targets
0.26Weak
trauma complicationOpen Targets
0.23Weak
frontotemporal dementiaOpen Targets
0.20Weak
mathematical abilityOpen Targets
0.11Weak
sign or symptomOpen Targets
0.06Suggestive
response to xenobiotic stimulusOpen Targets
0.06Suggestive
disease of peritoneumOpen Targets
0.05Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
Abnormality of the gastrointestinal tractOpen Targets
0.05Suggestive
delta-beta-thalassemiaOpen Targets
0.05Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.05Suggestive
dominant beta-thalassemiaOpen Targets
0.05Suggestive
placenta praeviaOpen Targets
0.04Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.04Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.04Suggestive
Hemoglobin C - beta-thalassemiaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GOLGA2Protein interaction100%LMAN1Protein interaction100%RAB1AProtein interaction100%USO1Protein interaction100%SEC22CProtein interaction100%SEC24BProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
85%
Liver
66%
Lung
61%
Ovary
59%
Brain
59%
Gene Interaction Network
Click a node to explore
SCFD1GOLGA2LMAN1RAB1AUSO1SEC22CSEC24B
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8WVM8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.81LoF Tolerant
pLIⓘ
0.23Tolerant
Observed/Expected LoF0.43 [0.24–0.81]
RankingsWhere SCFD1 stands among ~20K protein-coding genes
  • #3,939of 20,598
    Most Researched120 · top quartile
  • #6,783of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedSCFD1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Integrative multi-omics analysis reveal novel therapeutic targets for glioblastoma.
PMID: 40638267
Int J Surg · 2025
1.00
2
In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies.
PMID: 35246475
J Immunother Cancer · 2022
0.90
3
Prioritization of Drug Targets for Neurodegenerative Diseases by Integrating Genetic and Proteomic Data From Brain and Blood.
PMID: 36759259
Biol Psychiatry · 2023
0.80
4
Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis.
PMID: 27455348
Nat Genet · 2016
0.70
5
Artificial neural network inference analysis identified novel genes and gene interactions associated with skeletal muscle aging.
PMID: 39210538
J Cachexia Sarcopenia Muscle · 2024
0.60