EPS15

epidermal growth factor receptor pathway substrate 15, the group of EF-hand domain containing

Basic information

Region (hg38): 1:51354263-51519328

Links

ENSG00000085832 ∙ NCBI:2060 ∙ OMIM:600051 ∙ HGNC:3419 ∙ Uniprot:P42566 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPS15 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPS15 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						0
missense			39	1		40
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	39	1	0

Variants in EPS15

This is a list of pathogenic ClinVar variants found in the EPS15 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-51356744-C-G		not specified	Uncertain significance (May 29, 2024)
1-51356789-C-T		not specified	Uncertain significance (Aug 17, 2022)
1-51356822-C-T		not specified	Uncertain significance (Jun 12, 2023)
1-51356828-T-C		not specified	Uncertain significance (Sep 26, 2024)
1-51356840-A-G		not specified	Uncertain significance (Aug 11, 2022)
1-51361175-C-T		not specified	Uncertain significance (Dec 17, 2021)
1-51361176-T-A		not specified	Uncertain significance (Feb 15, 2023)
1-51361194-T-C		not specified	Uncertain significance (Feb 02, 2024)
1-51361211-T-C		not specified	Uncertain significance (Aug 05, 2024)
1-51361283-C-T		not specified	Uncertain significance (Oct 28, 2023)
1-51361310-A-G		not specified	Uncertain significance (Aug 02, 2022)
1-51363962-T-G		not specified	Uncertain significance (Oct 16, 2024)
1-51363965-T-C		not specified	Uncertain significance (Jun 21, 2023)
1-51364019-C-G		not specified	Uncertain significance (Jan 08, 2024)
1-51364024-T-C		not specified	Uncertain significance (Nov 20, 2024)
1-51366020-G-A		not specified	Uncertain significance (Aug 12, 2021)
1-51399048-T-C		not specified	Uncertain significance (Jan 26, 2023)
1-51399057-G-A		not specified	Uncertain significance (Feb 14, 2023)
1-51399078-G-A		not specified	Uncertain significance (Jan 06, 2023)
1-51400939-C-T		not specified	Uncertain significance (Aug 21, 2024)
1-51402437-C-T		not specified	Uncertain significance (Oct 13, 2023)
1-51402486-G-C		not specified	Uncertain significance (Feb 10, 2022)
1-51402492-T-A		not specified	Uncertain significance (Jan 03, 2024)
1-51402522-C-G		not specified	Uncertain significance (May 15, 2024)
1-51405957-T-C		not specified	Uncertain significance (Jan 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPS15	protein_coding	protein_coding	ENST00000371733	25	165066

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00348	0.997	125719	0	28	125747	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.781	402	449	0.896	0.0000213	5930
Missense in Polyphen		110	152.55	0.72108		2081
Synonymous	0.369	157	163	0.963	0.00000847	1635
Loss of Function	4.56	14	48.2	0.291	0.00000214	629

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000178	0.000178
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000168	0.000149
Middle Eastern	0.00	0.00
South Asian	0.000137	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Acts as a clathrin adapter required for post-Golgi trafficking. Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta- 1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. {ECO:0000269|PubMed:16903783, ECO:0000269|PubMed:18362181, ECO:0000269|PubMed:19458185, ECO:0000269|PubMed:22648170}.
• Disease: DISEASE: Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with KMT2A/MLL1. The result is a rogue activator protein.
• Pathway: Endocytosis - Homo sapiens (human);VEGFA-VEGFR2 Signaling Pathway;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;EGF-EGFR Signaling Pathway;Disease;Signal Transduction;Vesicle-mediated transport;endocytotic role of ndk phosphins and dynamin;Membrane Trafficking;Infectious disease;EGFR downregulation;Signaling by EGFR;Clathrin-mediated endocytosis;EGFR1;Cargo recognition for clathrin-mediated endocytosis;Notch signaling pathway;Negative regulation of MET activity;Signaling by MET;Signaling by Receptor Tyrosine Kinases;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Internalization of ErbB1;InlB-mediated entry of Listeria monocytogenes into host cell;Listeria monocytogenes entry into host cells (Consensus)

Recessive Scores

• pRec: 0.434

Intolerance Scores

• loftool: 0.667
• rvis_EVS: 0.47
• rvis_percentile_EVS: 78.83

Haploinsufficiency Scores

• pHI: 0.598
• hipred: Y
• hipred_score: 0.731
• ghis: 0.549

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.704

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eps15
• Phenotype: hematopoietic system phenotype; immune system 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: positive regulation of receptor recycling;Golgi to endosome transport;epidermal growth factor receptor signaling pathway;cell population proliferation;vesicle organization;receptor-mediated endocytosis of virus by host cell;endocytic recycling;negative regulation of epidermal growth factor receptor signaling pathway;regulation of cell population proliferation;viral entry into host cell;clathrin coat assembly;membrane organization;postsynaptic neurotransmitter receptor internalization
• Cellular component: cytosol;plasma membrane;clathrin-coated pit;basal plasma membrane;membrane;aggresome;apical plasma membrane;AP-2 adaptor complex;early endosome membrane;intracellular membrane-bounded organelle;ciliary membrane;postsynapse;glutamatergic synapse
• Molecular function: calcium ion binding;protein binding;SH3 domain binding;polyubiquitin modification-dependent protein binding;cargo receptor activity;identical protein binding;cadherin binding