EPS15L1

epidermal growth factor receptor pathway substrate 15 like 1, the group of EF-hand domain containing

Basic information

Region (hg38): 19:16355225-16472085

Links

ENSG00000127527 ∙ NCBI:58513 ∙ OMIM:616826 ∙ HGNC:24634 ∙ Uniprot:Q9UBC2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• split hand-foot malformation (Supportive), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPS15L1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPS15L1 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			40			40
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	40	0	0

Variants in EPS15L1

This is a list of pathogenic ClinVar variants found in the EPS15L1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-16361784-T-C		not specified	Uncertain significance (Nov 17, 2022)
19-16361883-T-C		not specified	Uncertain significance (Oct 20, 2023)
19-16361920-C-G		not specified	Uncertain significance (Jan 09, 2024)
19-16361940-C-T		not specified	Uncertain significance (Dec 20, 2021)
19-16361979-T-A		not specified	Uncertain significance (Mar 28, 2024)
19-16377132-T-A		not specified	Uncertain significance (Dec 21, 2022)
19-16377149-C-G		not specified	Uncertain significance (Mar 02, 2023)
19-16377163-G-C		not specified	Uncertain significance (May 16, 2023)
19-16377173-G-C		not specified	Uncertain significance (Dec 01, 2022)
19-16377236-A-G		not specified	Uncertain significance (Jan 22, 2024)
19-16377251-G-A		not specified	Uncertain significance (Jan 04, 2022)
19-16392322-G-C		not specified	Uncertain significance (Apr 13, 2022)
19-16392399-G-A		not specified	Uncertain significance (Nov 01, 2022)
19-16393995-G-A		not specified	Uncertain significance (Dec 21, 2022)
19-16393996-G-A		not specified	Uncertain significance (Nov 10, 2022)
19-16395379-T-C		not specified	Uncertain significance (Jun 29, 2023)
19-16395424-G-A		not specified	Uncertain significance (May 31, 2023)
19-16402380-C-T		not specified	Likely benign (Apr 17, 2024)
19-16402451-C-A		not specified	Uncertain significance (Apr 11, 2023)
19-16402452-G-A		not specified	Uncertain significance (Aug 03, 2022)
19-16402454-C-T		not specified	Uncertain significance (Nov 08, 2022)
19-16403758-T-C		not specified	Conflicting classifications of pathogenicity (Sep 13, 2023)
19-16403849-C-T		not specified	Uncertain significance (Nov 08, 2022)
19-16404637-C-T		not specified	Conflicting classifications of pathogenicity (Mar 01, 2024)
19-16404644-T-C		not specified	Uncertain significance (May 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPS15L1	protein_coding	protein_coding	ENST00000455140	24	116847

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000363	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.90	417	542	0.770	0.0000322	6002
Missense in Polyphen		111	182.89	0.60691		2116
Synonymous	0.746	220	235	0.938	0.0000164	1739
Loss of Function	5.90	7	53.6	0.131	0.00000293	579

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000973	0.0000879
Middle Eastern	0.000109	0.000109
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. 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:22648170, ECO:0000269|PubMed:9407958}.
• Pathway: Endocytosis - Homo sapiens (human);EGF-EGFR Signaling Pathway;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;EGFR downregulation;Signaling by EGFR;Clathrin-mediated endocytosis;Cargo recognition for clathrin-mediated endocytosis;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.127

Intolerance Scores

• loftool: 0.269
• rvis_EVS: -2.13
• rvis_percentile_EVS: 1.51

Haploinsufficiency Scores

• pHI: 0.146
• hipred: Y
• hipred_score: 0.756
• ghis: 0.654

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.603

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eps15l1

Zebrafish Information Network

• Gene name: eps15l1b
• Affected structure: T cell differentiation in thymus
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: endocytosis;negative regulation of epidermal growth factor receptor signaling pathway;membrane organization
• Cellular component: nucleus;cytosol;plasma membrane;membrane;clathrin coat of coated pit
• Molecular function: calcium ion binding;protein binding;cadherin binding