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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SEC23IP
SEC23 interacting protein
Chromosome 10 · 10q26.11-q26.12
NCBI Gene: 11196Ensembl: ENSG00000107651.15HGNC: HGNC:17018UniProt: A0A994J542
109PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingprotein bindingGolgi apparatusglycerophospholipase activityParkinson diseasetype 2 diabetes mellituscardiomyopathyGenu valgum
✦AI Summary

SEC23IP (SEC23 interacting protein) is a regulatory protein localized at ER exit sites (ERES) that plays a central role in endoplasmic reticulum-to-Golgi transport. SEC23IP contains a conserved SAM-DDHD domain module that recognizes phosphatidylinositol phosphates (PI3P, PI4P, PI5P) and phosphatidic acid, using lipid signals to control COPII coat assembly and spatial organization at ERES 1. Functionally, SEC23IP recruits the lipid transfer protein VPS13B/COH1 to ERES-Golgi interfaces, promoting tubular ERGIC formation and facilitating ER export of cargo including procollagen 2. SEC23IP knockout impairs this trafficking pathway, suggesting relevance to Cohen syndrome pathogenesis. Clinically, SEC23IP has been implicated in multiple disorders. Homozygous truncating variants in SEC23IP were identified in consanguineous families with neurodevelopmental disorders 3, while rare coding variants at the SEC23IP locus showed significant association with adult ADHD 4. In neurodegenerative diseases, SEC23IP emerged as a candidate therapeutic target for Parkinson's disease through integrative genetic and proteomic analysis 5, though large-scale exome sequencing found no statistically significant rare variant enrichment 6. Additionally, SEC23IP gene fusions have been detected in myxoinflammatory fibroblastic sarcoma 7. These findings indicate SEC23IP functions as a key ERES organizer with implications for both developmental and neurodegenerative disease pathogenesis.

Sources cited
1
SEC23IP (p125A) contains a SAM-DDHD domain that recognizes phospholipids and controls COPII coat assembly at ERES
PMID: 24522181
2
SEC23IP recruits VPS13B to ERES-Golgi interface, regulates tubular ERGIC formation, and affects procollagen secretion
PMID: 39352497
3
Homozygous truncating SEC23IP variants identified in consanguineous families with neurodevelopmental disorders
PMID: 28097321
4
SEC23IP locus shows significant association with adult ADHD through rare coding variants
PMID: 27754487
5
SEC23IP identified as candidate drug target for Parkinson's disease through Mendelian randomization analysis
PMID: 36759259
6
SEC23IP showed trend for rare variant enrichment in Parkinson's disease but did not survive multiple testing correction
PMID: 33002040
7
SEC23IP::VGLL3 gene fusion detected in myxoinflammatory fibroblastic sarcoma with potential TEAD pathway activation
PMID: 35776191
Disease Associationsⓘ20
Parkinson diseaseOpen Targets
0.40Moderate
type 2 diabetes mellitusOpen Targets
0.38Weak
cardiomyopathyOpen Targets
0.38Weak
Genu valgumOpen Targets
0.30Weak
Genu varumOpen Targets
0.29Weak
diabetes mellitusOpen Targets
0.28Weak
goutOpen Targets
0.15Weak
venous thromboembolismOpen Targets
0.12Weak
dermatomycosisOpen Targets
0.12Weak
azoospermiaOpen Targets
0.10Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
spermatogenic failure 78Open Targets
0.07Suggestive
spermatogenic failure 86Open Targets
0.06Suggestive
spermatogenic failure 85Open Targets
0.06Suggestive
spermatogenic failure, X-linked, 7Open Targets
0.06Suggestive
spermatogenic failure 42Open Targets
0.06Suggestive
spermatogenic failure 6Open Targets
0.06Suggestive
spermatogenic failure 20Open Targets
0.06Suggestive
Male infertility due to large-headed multiflagellar polyploid spermatozoaOpen Targets
0.06Suggestive
spermatogenic failure 5Open Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SEC31AProtein interaction100%SCFD1Protein interaction79%SEC13Protein interaction78%SEC24CProtein interaction78%SEC24DProtein interaction78%PDCD6Protein interaction78%
Tissue Expression6 tissues
Liver
100%
Lung
99%
Ovary
91%
Heart
90%
Brain
75%
Bone Marrow
48%
Gene Interaction Network
Click a node to explore
SEC23IPSEC31ASCFD1SEC13SEC24CSEC24DPDCD6
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9Y6Y8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.86LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.69 [0.56–0.86]
RankingsWhere SEC23IP stands among ~20K protein-coding genes
  • #4,381of 20,598
    Most Researched109 · top quartile
  • #7,592of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedSEC23IP
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.
PMID: 28097321
JAMA Psychiatry · 2017
1.00
2
Prioritization of Drug Targets for Neurodegenerative Diseases by Integrating Genetic and Proteomic Data From Brain and Blood.
PMID: 36759259
Biol Psychiatry · 2023
0.90
3
Sec23IP recruits VPS13B/COH1 to ER exit site-Golgi interface for tubular ERGIC formation.
PMID: 39352497
J Cell Biol · 2024
0.80
4
RNA-sequencing of myxoinflammatory fibroblastic sarcomas reveals a novel SND1::BRAF fusion and 3 different molecular aberrations with the potential to upregulate the TEAD1 gene including SEC23IP::VGLL3 and TEAD1::MRTFB gene fusions.
PMID: 35776191
Virchows Arch · 2022
0.70
5
A cascade of ER exit site assembly that is regulated by p125A and lipid signals.
PMID: 24522181
J Cell Sci · 2014
0.60