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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ERLIN2
ER lipid raft associated 2
Chromosome 8 Β· 8p11.23
NCBI Gene: 11160Ensembl: ENSG00000147475.18HGNC: HGNC:1356UniProt: A0A384ME54
193PubMed Papers
22Diseases
0Drugs
34Pathogenic Variants
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingendoplasmic reticulummembrane raftprotein-containing complexhereditary spastic paraplegia 18Autosomal recessive spastic paraplegia type 18hereditary spastic paraplegiaspastic paraplegia 18b, autosomal recessive
✦AI Summary

ERLIN2 encodes an endoplasmic reticulum (ER) membrane protein that forms oligomeric complexes crucial for cellular quality control and metabolic regulation. The protein assembles into cage-like structures containing 13 pairs of ERLIN1-ERLIN2 heterodimers or 26 ERLIN2 homodimers, serving as platforms for protein degradation pathways 1. ERLIN2 participates in endoplasmic reticulum-associated degradation (ERAD) and regulates cholesterol homeostasis through the SREBP signaling pathway 2. The protein interacts with various partners including SCAP-SREBF complexes and can stabilize proteins like SREBP1 by inhibiting ubiquitination 3. ERLIN2 mutations are associated with hereditary spastic paraplegia (HSP), specifically types 18A (autosomal dominant) and 18B (autosomal recessive) 4. Disease-causing variants can activate ER stress responses and alter axonal development, with a novel V71A variant demonstrating increased XBP-1S mRNA levels and modified ER morphology 5. The protein also plays roles in cancer biology, where it can influence tumor cell proliferation and metastasis through stabilization of cell cycle regulators like Cyclin B1 6.

Sources cited
1
ERLIN2 forms cage-like oligomeric structures with 13 ERLIN1-ERLIN2 heterodimers or 26 ERLIN2 homodimers
PMID: 41481136
2
ERLIN2 regulates cholesterol homeostasis through SREBP signaling pathway and SCAP interaction
PMID: 37647408
3
ERLIN2 stabilizes SREBP1 protein by inhibiting its ubiquitination
PMID: 40550808
4
ERLIN2 mutations cause hereditary spastic paraplegia types 18A and 18B
PMID: 23897027
5
Disease-causing ERLIN2 variants activate ER stress and affect axonal development
PMID: 37752894
6
ERLIN2 influences cancer cell behavior through Cyclin B1 stabilization
PMID: 37831636
Disease Associationsβ“˜22
hereditary spastic paraplegia 18Open Targets
0.76Strong
Autosomal recessive spastic paraplegia type 18Open Targets
0.74Strong
hereditary spastic paraplegiaOpen Targets
0.63Moderate
spastic paraplegia 18b, autosomal recessiveOpen Targets
0.61Moderate
cancerOpen Targets
0.59Moderate
autosomal dominant complex spastic paraplegiaOpen Targets
0.57Moderate
bone development diseaseOpen Targets
0.56Moderate
Spastic paraplegiaOpen Targets
0.54Moderate
NeurodegenerationOpen Targets
0.50Moderate
cystic fibrosisOpen Targets
0.46Moderate
spastic paraplegia 18a, autosomal dominantOpen Targets
0.46Moderate
Intellectual disabilityOpen Targets
0.37Weak
juvenile primary lateral sclerosisOpen Targets
0.37Weak
Recessive intellectual disability - motor dysfunction - multiple joint contracturesOpen Targets
0.37Weak
recessive intellectual disability-motor dysfunction-multiple joint contractures syndromeOpen Targets
0.37Weak
autosomal recessive non-syndromic intellectual disabilityOpen Targets
0.37Weak
Abnormality of the nervous systemOpen Targets
0.27Weak
genetic disorderOpen Targets
0.19Weak
squamous cell carcinomaOpen Targets
0.19Weak
Spastic paraparesisOpen Targets
0.12Weak
Spastic paraplegia 18A, autosomal dominantUniProt
Spastic paraplegia 18B, autosomal recessiveUniProt
Pathogenic Variants34
NM_007175.8(ERLIN2):c.452C>T (p.Ala151Val)Pathogenic
Spastic paraplegia|Spastic paraplegia 18a, autosomal dominant|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 151
NM_007175.8(ERLIN2):c.502G>A (p.Val168Met)Pathogenic
not provided|Spastic paraplegia|Spastic paraplegia 18a, autosomal dominant
β˜…β˜…β˜†β˜†2025β†’ Residue 168
NM_007175.8(ERLIN2):c.187C>A (p.Gln63Lys)Pathogenic
Spastic paraplegia|Hereditary spastic paraplegia
β˜…β˜…β˜†β˜†2022β†’ Residue 63
NM_007175.8(ERLIN2):c.207T>A (p.Asp69Glu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 69
NM_007175.8(ERLIN2):c.237-1G>APathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_007175.8(ERLIN2):c.684del (p.Tyr229fs)Pathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2025β†’ Residue 229
NM_007175.8(ERLIN2):c.969_973del (p.Ser324fs)Likely pathogenic
Spastic paraplegia 18b, autosomal recessive
β˜…β˜†β˜†β˜†2024β†’ Residue 324
NM_007175.8(ERLIN2):c.660del (p.Val221fs)Pathogenic
Hereditary spastic paraplegia 18
β˜…β˜†β˜†β˜†2024β†’ Residue 221
NM_007175.8(ERLIN2):c.367G>T (p.Glu123Ter)Pathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2024β†’ Residue 123
NM_007175.8(ERLIN2):c.303del (p.Val100_Tyr101insTer)Pathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2023β†’ Residue 100
NM_007175.8(ERLIN2):c.47_48delinsAA (p.Cys16Ter)Pathogenic
Hereditary spastic paraplegia 18
β˜…β˜†β˜†β˜†2023β†’ Residue 16
NM_007175.8(ERLIN2):c.853A>T (p.Lys285Ter)Pathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2023β†’ Residue 285
NM_007175.8(ERLIN2):c.107+2T>CLikely pathogenic
Hereditary spastic paraplegia 18
β˜…β˜†β˜†β˜†2023
NM_007175.8(ERLIN2):c.819+2T>CLikely pathogenic
Spastic paraplegia 18b, autosomal recessive
β˜…β˜†β˜†β˜†2023
NM_007175.8(ERLIN2):c.179dup (p.Ser61fs)Pathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2023β†’ Residue 61
NM_007175.8(ERLIN2):c.207T>G (p.Asp69Glu)Likely pathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2022β†’ Residue 69
NM_007175.8(ERLIN2):c.532G>A (p.Ala178Thr)Likely pathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2022β†’ Residue 178
NM_007175.8(ERLIN2):c.549del (p.Asn182_Tyr183insTer)Likely pathogenic
Abnormality of the nervous system
β˜…β˜†β˜†β˜†2021β†’ Residue 182
NM_007175.8(ERLIN2):c.303T>A (p.Tyr101Ter)Pathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2021β†’ Residue 101
NM_007175.8(ERLIN2):c.237-2A>GLikely pathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2020
View on ClinVar β†—
Related Genes
UBAC2Protein interaction100%SYVN1Protein interaction99%DERL1Protein interaction99%ITPR1Protein interaction92%VCPProtein interaction88%FAF2Protein interaction87%
Tissue Expression6 tissues
Liver
100%
Brain
97%
Heart
89%
Ovary
79%
Bone Marrow
61%
Lung
47%
Gene Interaction Network
Click a node to explore
ERLIN2UBAC2SYVN1DERL1ITPR1VCPFAF2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O94905
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.70LoF Tolerant
pLIβ“˜
0.01Tolerant
Observed/Expected LoF0.48 [0.34–0.70]
RankingsWhere ERLIN2 stands among ~20K protein-coding genes
  • #2,218of 20,598
    Most Researched193 Β· top quartile
  • #1,693of 5,498
    Most Pathogenic Variants34
  • #5,355of 17,882
    Most Constrained (LOEUF)0.70
Genes detectedERLIN2
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms.
PMID: 23897027
Acta Neuropathol Β· 2013
1.00
2
Inhibiting sorting nexin 10 promotes mucosal healing through SREBP2-mediated stemness restoration of intestinal stem cells.
PMID: 37647408
Sci Adv Β· 2023
0.90
3
ERLIN1/2 scaffolds bridge TMUB1 and RNF170 and restrict cholesterol esterification to regulate the secretory pathway.
PMID: 38782601
Life Sci Alliance Β· 2024
0.88
4
CLPTM1L interacts with ERLIN2 to stabilize SREBP1 and drive tumorigenesis in nasopharyngeal carcinoma.
PMID: 40550808
Cell Death Dis Β· 2025
0.80
5
Structural insights into the organization of the human Erlin complex.
PMID: 41481136
J Mol Cell Biol Β· 2026
0.70