ERLIN2

ER lipid raft associated 2

Basic information

Region (hg38): 8:37736601-37758422

Previous symbols: [ "C8orf2", "SPFH2", "SPG18" ]

Links

ENSG00000147475 ∙ NCBI:11160 ∙ OMIM:611605 ∙ HGNC:1356 ∙ Uniprot:O94905 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 18 (Moderate), mode of inheritance: AR
• hereditary spastic paraplegia 18 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 18 (Supportive), mode of inheritance: AR
• juvenile primary lateral sclerosis (Supportive), mode of inheritance: AR
• recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 18A, autosomal dominant; Spastic paraplegia 18B, autosomal recessive	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	21330303; 23109145; 29528531; 32094424

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ERLIN2 gene.

• Spastic paraplegia (6 variants)
• Hereditary spastic paraplegia 18 (4 variants)
• Hereditary spastic paraplegia (2 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ERLIN2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	26	2	31
missense	4	4	49			57
nonsense	4	1				5
start loss						0
frameshift	5	3				8
inframe indel			3			3
splice donor/acceptor (+/-2bp)		2				2
splice region	1		5	3	2	11
non coding				27	10	37
Total	13	10	55	53	12

Variants in ERLIN2

This is a list of pathogenic ClinVar variants found in the ERLIN2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-37736652-G-C		not specified	Likely benign (Mar 03, 2016)
8-37737938-GC-G			Pathogenic (Mar 03, 2016)
8-37737943-T-G		Spastic paraplegia	Likely benign (Nov 24, 2022)
8-37737958-C-A			Uncertain significance (Jun 26, 2015)
8-37737961-T-C		Hereditary spastic paraplegia	Conflicting classifications of pathogenicity (Apr 19, 2021)
8-37737964-CT-C		Spastic paraplegia	Pathogenic (Dec 28, 2018)
8-37737969-GT-AA		Hereditary spastic paraplegia 18	Pathogenic (Sep 05, 2023)
8-37737972-C-T			Uncertain significance (Oct 14, 2020)
8-37737998-A-T		Spastic paraplegia	Uncertain significance (Jul 19, 2022)
8-37737999-T-C		Spastic paraplegia	Uncertain significance (Nov 26, 2022)
8-37738016-G-T		Spastic paraplegia	Uncertain significance (May 27, 2017)
8-37738028-A-G		Spastic paraplegia	Uncertain significance (Oct 01, 2022)
8-37738042-CAG-C		Spastic paraplegia	Likely benign (Aug 03, 2023)
8-37738123-A-G			Benign (Sep 18, 2018)
8-37738225-A-G			Likely benign (Dec 17, 2018)
8-37740350-C-T		Spastic paraplegia	Likely benign (Apr 23, 2023)
8-37740380-G-A		not specified • Spastic paraplegia	Conflicting classifications of pathogenicity (Jan 29, 2024)
8-37740386-G-A			Likely benign (Jun 15, 2018)
8-37740393-G-A		Inborn genetic diseases • Spastic paraplegia	Uncertain significance (Aug 31, 2022)
8-37740401-T-C		Spastic paraplegia	Likely benign (May 20, 2022)
8-37740405-C-T		Spastic paraplegia	Uncertain significance (Aug 19, 2019)
8-37740411-A-C		Spastic paraplegia	Uncertain significance (Jun 28, 2023)
8-37740434-T-C		Spastic paraplegia	Likely benign (Mar 07, 2023)
8-37740434-T-TA		Spastic paraplegia	Pathogenic (Apr 09, 2023)
8-37740444-C-A		Spastic paraplegia • Hereditary spastic paraplegia	Pathogenic/Likely pathogenic (May 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ERLIN2	protein_coding	protein_coding	ENST00000276461	11	22503

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000667	0.981	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.88	108	179	0.605	0.00000982	2243
Missense in Polyphen		41	79.171	0.51787		1001
Synonymous	0.350	66	69.7	0.947	0.00000441	627
Loss of Function	2.08	8	17.3	0.462	7.66e-7	237

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.000163	0.000163
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs) such as ITPR1 (PubMed:19240031, PubMed:17502376). Promotes sterol-accelerated ERAD of HMGCR probably implicating an AMFR/gp78-containing ubiquitin ligase complex (PubMed:21343306). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway. May promote ER retention of the SCAP-SREBF complex (PubMed:24217618). {ECO:0000269|PubMed:17502376, ECO:0000269|PubMed:19240031, ECO:0000269|PubMed:21343306, ECO:0000269|PubMed:24217618}.
• Pathway: Disorders of transmembrane transporters;Disease;Defective CFTR causes cystic fibrosis;Transport of small molecules;ABC-family proteins mediated transport;Signaling by FGFR in disease;Signaling by plasma membrane FGFR1 fusions;FGFR1 mutant receptor activation;Signaling by FGFR1 in disease;ABC transporter disorders;Diseases of signal transduction (Consensus)

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.253
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.09

Haploinsufficiency Scores

• pHI: 0.323
• hipred: Y
• hipred_score: 0.685
• ghis: 0.613

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.712

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Erlin2
• Phenotype: skeleton phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: cholesterol metabolic process;peptidyl-tyrosine phosphorylation;ubiquitin-dependent ERAD pathway;SREBP signaling pathway;negative regulation of cholesterol biosynthetic process;negative regulation of fatty acid biosynthetic process;transmembrane transport
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;plasma membrane;integral component of membrane;protein-containing complex;membrane raft
• Molecular function: protein tyrosine kinase activity;protein binding;cholesterol binding;ubiquitin protein ligase binding