EMP2

epithelial membrane protein 2

Basic information

Region (hg38): 16:10528422-10580632

Links

ENSG00000213853

∙ NCBI:2013 ∙ OMIM:602334 ∙ HGNC:3334 ∙ Uniprot:P54851 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

nephrotic syndrome, type 10 (Limited), mode of inheritance: AR
familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
nephrotic syndrome, type 10 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephrotic syndrome, type 10	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	Renal	24814193
Management with cyclophosphamide has been described as beneficial (frequent relapses have been described with steroid treatment)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EMP2 gene.

not_provided (47 variants)
not_specified (30 variants)
Nephrotic_syndrome,_type_10 (8 variants)
EMP2-related_disorder (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EMP2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001424.6. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				18 clinvar	2 clinvar	20
missense	1 clinvar		36 clinvar	3 clinvar		40
nonsense		1 clinvar	1 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
Total	1	2	38	21	2

Highest pathogenic variant AF is 0.0000328402

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EMP2	protein_coding	protein_coding	ENST00000359543	4	52277

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.39e-7	0.0870	125723	0	23	125746	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.440	118	105	1.12	0.00000644	1106
Missense in Polyphen		50	44.508	1.1234		509
Synonymous	-0.139	45	43.8	1.03	0.00000316	314
Loss of Function	-0.703	9	6.99	1.29	2.98e-7	78

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000235	0.000235
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000704	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Functions as a key regulator of cell membrane composition by regulating proteins surface expression. Also, plays a role in regulation of processes including cell migration, cell proliferation, cell contraction and cell adhesion. Negatively regulates caveolae formation by reducing CAV1 expression and CAV1 amount by increasing lysosomal degradation (PubMed:24814193). Facilitates surface trafficking and formation of lipid rafts bearing GPI-anchor proteins (By similarity). Regulates surface expression of MHC1 and ICAM1 proteins increasing susceptibility to T-cell mediated cytotoxicity (By similarity). Regulates the plasma membrane expression of the integrin heterodimers ITGA6-ITGB1, ITGA5-ITGB3 and ITGA5-ITGB1 resulting in modulation of cell-matrix adhesion (PubMed:16216233). Also regulates many processes through PTK2. Regulates blood vessel endothelial cell migration and angiogenesis by regulating VEGF protein expression through PTK2 activation (PubMed:23439602). Regulates cell migration and cell contraction through PTK2 and SRC activation (PubMed:21637765, PubMed:22728127). Regulates focal adhesion density, F-actin conformation and cell adhesion capacity through interaction with PTK2 (PubMed:19494199). Positively regulates cell proliferation (PubMed:24814193). Plays a role during cell death and cell blebbing (PubMed:12107182). Promotes angiogenesis and vasculogenesis through induction of VEGFA via a HIF1A-dependent pathway (PubMed:23334331). Also plays a role in embryo implantation by regulating surface trafficking of integrin heterodimer ITGA5-ITGB3 (PubMed:16487956). May play a role in glomerular filtration (By similarity). {ECO:0000250|UniProtKB:F1QIK8, ECO:0000250|UniProtKB:O88662, ECO:0000269|PubMed:12107182, ECO:0000269|PubMed:16216233, ECO:0000269|PubMed:16487956, ECO:0000269|PubMed:19494199, ECO:0000269|PubMed:21637765, ECO:0000269|PubMed:22728127, ECO:0000269|PubMed:23334331, ECO:0000269|PubMed:23439602, ECO:0000269|PubMed:24814193}.;
Disease: DISEASE: Nephrotic syndrome 10 (NPHS10) [MIM:615861]: A form of nephrotic syndrome, a renal disease clinically characterized by focal segmental glomerulosclerosis, progressive renal failure, severe proteinuria, hypoalbuminemia, hyperlipidemia and edema. NPHS10 is a steroid-sensitive form characterized by onset in childhood and remission without end-stage kidney disease. {ECO:0000269|PubMed:24814193}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

loftool: 0.300
rvis_EVS: -0.36
rvis_percentile_EVS: 28.93

Haploinsufficiency Scores

pHI: 0.0867
hipred: N
hipred_score: 0.216
ghis: 0.510

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.645

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Emp2
Phenotype: embryo phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; immune system phenotype; endocrine/exocrine gland phenotype;

Zebrafish Information Network

Gene name: emp2
Affected structure: orbit
Phenotype tag: abnormal
Phenotype quality: edematous

Gene ontology

Biological process: membrane raft assembly;T cell mediated cytotoxicity;regulation of cell-matrix adhesion;positive regulation of cell-matrix adhesion;regulation of glomerular filtration;actin filament organization;cell adhesion;cell-matrix adhesion;embryo implantation;cell death;cell population proliferation;positive regulation of cell population proliferation;regulation of endothelial cell migration;cell migration;bleb assembly;activation of protein kinase activity;protein localization to cell surface;blood vessel endothelial cell migration;regulation of kinase activity;early endosome to late endosome transport;regulation of angiogenesis;actin-mediated cell contraction;caveola assembly;protein localization to plasma membrane;positive regulation of integrin-mediated signaling pathway;regulation of vasculogenesis
Cellular component: Golgi membrane;nucleus;cytoplasm;Golgi apparatus;cytosol;plasma membrane;caveola;cell surface;integral component of membrane;apical plasma membrane;cytoplasmic vesicle;membrane raft;apical part of cell
Molecular function: integrin binding;protein binding;kinase binding;protein kinase binding