EPG5

ectopic P-granules 5 autophagy tethering factor

Basic information

Region (hg38): 18:45800580-45967329

Previous symbols: [ "KIAA1632" ]

Links

ENSG00000152223 ∙ NCBI:57724 ∙ OMIM:615068 ∙ HGNC:29331 ∙ Uniprot:Q9HCE0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Vici syndrome (Definitive), mode of inheritance: AR
• Vici syndrome (Strong), mode of inheritance: AR
• Vici syndrome (Strong), mode of inheritance: AR
• Vici syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vici syndrome	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Surveillance for cardiomyopathy (eg, including echocardiogram) may allow early management; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	20186778; 23222957; 27343256; 28168853

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPG5 gene.

• Vici syndrome (1513 variants)
• not provided (264 variants)
• Inborn genetic diseases (147 variants)
• not specified (28 variants)
• - (9 variants)
• EPG5-related condition (8 variants)
• Global developmental delay (1 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPG5 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			6	360	20	386
missense		2	718	29	19	768
nonsense	42	18	2			62
start loss		1				1
frameshift	39	7	1			47
inframe indel			10			10
splice donor/acceptor (+/-2bp)	8	11	2			21
splice region		1	33	52	8	94
non coding			27	220	104	351
Total	89	39	766	609	143

Highest pathogenic variant AF is 0.0000526

Variants in EPG5

This is a list of pathogenic ClinVar variants found in the EPG5 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-45800871-A-G		not specified	Benign (Jan 24, 2024)
18-45825763-C-T		not specified	Likely benign (May 17, 2023)
18-45837066-C-G		not specified	Uncertain significance (Feb 16, 2023)
18-45837069-G-C		not specified	Uncertain significance (Sep 01, 2021)
18-45837513-G-T		not specified	Uncertain significance (May 31, 2023)
18-45837558-G-C		not specified	Uncertain significance (Jan 16, 2024)
18-45837570-G-A		not specified	Uncertain significance (Nov 08, 2022)
18-45837585-T-G		not specified	Uncertain significance (Jan 03, 2024)
18-45837590-T-G		not specified	Uncertain significance (Oct 12, 2021)
18-45837639-T-C		not specified	Uncertain significance (Jul 20, 2021)
18-45837693-C-T		not specified	Uncertain significance (Dec 11, 2023)
18-45837696-G-C		not specified	Uncertain significance (Mar 01, 2023)
18-45837733-C-G		not specified	Uncertain significance (Sep 06, 2022)
18-45837782-C-A		not specified	Uncertain significance (Oct 04, 2022)
18-45837788-G-C		not specified	Uncertain significance (Jul 26, 2022)
18-45837872-C-T		not specified	Uncertain significance (Apr 25, 2023)
18-45838724-C-G			Uncertain significance (Oct 01, 2023)
18-45838754-G-C		not specified	Uncertain significance (Oct 12, 2021)
18-45838756-C-G		not specified	Uncertain significance (Dec 14, 2022)
18-45838759-G-A		not specified	Uncertain significance (Jun 09, 2022)
18-45838772-G-A		not specified	Uncertain significance (Feb 06, 2023)
18-45838826-C-A		not specified	Uncertain significance (Aug 02, 2021)
18-45838827-G-A			Likely benign (Dec 01, 2022)
18-45838834-G-T		not specified	Uncertain significance (Mar 04, 2024)
18-45838852-G-A		not specified	Uncertain significance (Oct 20, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPG5	protein_coding	protein_coding	ENST00000282041	44	119667

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.35e-13	1.00	124715	0	112	124827	0.000449

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.08	1233	1.34e+3	0.917	0.0000699	16923
Missense in Polyphen		598	690.76	0.86571		9074
Synonymous	-0.950	548	520	1.05	0.0000282	4979
Loss of Function	6.88	48	134	0.358	0.00000684	1556

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00131	0.00124
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.000564	0.000556
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000454	0.000450
Middle Eastern	0.000564	0.000556
South Asian	0.000327	0.000327
Other	0.000496	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in autophagy. May play a role in a late step of autophagy, such as clearance of autophagosomal cargo. {ECO:0000269|PubMed:20550938, ECO:0000269|PubMed:23222957}.
• Disease: DISEASE: Vici syndrome (VICIS) [MIM:242840]: A rare congenital multisystem disorder characterized by agenesis of the corpus callosum, cataracts, pigmentary defects, progressive cardiomyopathy, and variable immunodeficiency. Affected individuals also have profound psychomotor retardation and hypotonia due to a myopathy. {ECO:0000269|PubMed:23222957}. Note=The disease is caused by mutations affecting the gene represented in this entry. Affected individuals show homozygosity or compound heterozygosity for truncating mutations, aberrant splicing and/or missense mutations. Parental studies suggest recessive inheritance with no carrier manifestation (PubMed:23222957). {ECO:0000269|PubMed:23222957}.

Recessive Scores

• pRec: 0.0999

Intolerance Scores

• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.31

Haploinsufficiency Scores

• pHI: 0.228
• hipred: N
• hipred_score: 0.492
• ghis: 0.554

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Epg5
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; cellular phenotype; immune system phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); growth/size/body region phenotype; muscle phenotype

Gene ontology

• Biological process: autophagy;autophagosome maturation
• Cellular component: cytoplasm