EXPH5

exophilin 5

Basic information

Region (hg38): 11:108505435-108593768

Links

ENSG00000110723 ∙ NCBI:23086 ∙ OMIM:612878 ∙ HGNC:30578 ∙ Uniprot:Q8NEV8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive (Strong), mode of inheritance: AR
• epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive (Strong), mode of inheritance: AR
• epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive (Strong), mode of inheritance: AR
• epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive (Strong), mode of inheritance: AR
• epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive	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	Dermatologic	23176819
Though appropriate skin care may be beneficial, it is unclear if early (genetic) diagnosis would be additionally advantageous

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EXPH5 gene.

• Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive (3 variants)
• not provided (2 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EXPH5 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				20	11	31
missense			119	25	26	170
nonsense	1		2			3
start loss						0
frameshift	4		1			5
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				3	7	10
Total	5	0	122	48	44

Highest pathogenic variant AF is 0.0000263

Variants in EXPH5

This is a list of pathogenic ClinVar variants found in the EXPH5 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-108509254-A-G			Benign (Jun 19, 2021)
11-108509396-G-GA			Likely benign (May 23, 2021)
11-108509554-T-C			Conflicting classifications of pathogenicity (Jan 03, 2024)
11-108509585-T-C		Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive	Benign (Jan 29, 2024)
11-108509593-T-C		Inborn genetic diseases	Uncertain significance (Jan 25, 2023)
11-108509608-C-C			Benign (Jan 29, 2024)
11-108509643-G-A			Uncertain significance (Oct 05, 2021)
11-108509712-G-A		Inborn genetic diseases	Uncertain significance (Sep 07, 2022)
11-108509720-AG-A		Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive	Pathogenic (Aug 04, 2022)
11-108509752-G-C		Inborn genetic diseases	Uncertain significance (Nov 06, 2023)
11-108509770-G-T		Inborn genetic diseases	Uncertain significance (Nov 06, 2023)
11-108509793-A-G		Inborn genetic diseases	Uncertain significance (Jun 13, 2024)
11-108509797-A-G		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
11-108509826-T-C		Inborn genetic diseases	Uncertain significance (Jun 01, 2023)
11-108509854-C-T		Inborn genetic diseases	Uncertain significance (Jul 12, 2022)
11-108509878-C-A		Inborn genetic diseases	Uncertain significance (May 08, 2023)
11-108509882-C-T		EXPH5-related disorder	Benign (Dec 15, 2023)
11-108509893-T-C		EXPH5-related disorder	Benign (Jan 19, 2024)
11-108509902-C-T		Inborn genetic diseases	Likely benign (Apr 08, 2022)
11-108509943-A-C			Likely benign (Aug 07, 2023)
11-108509988-G-T		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
11-108510013-G-C		EXPH5-related disorder	Benign (May 05, 2023)
11-108510028-C-A		Inborn genetic diseases	Uncertain significance (Oct 25, 2023)
11-108510036-G-A		Inborn genetic diseases	Uncertain significance (Mar 28, 2024)
11-108510054-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 30, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EXPH5	protein_coding	protein_coding	ENST00000265843	6	88308

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.16e-26	0.181	125524	0	224	125748	0.000891

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.274	1025	1.00e+3	1.02	0.0000479	13092
Missense in Polyphen		195	222.63	0.87589		3194
Synonymous	0.605	361	376	0.960	0.0000194	3810
Loss of Function	1.93	49	65.9	0.743	0.00000349	906

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00205	0.00205
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.00136	0.00136
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.00107	0.00106
Middle Eastern	0.00136	0.00136
South Asian	0.000668	0.000653
Other	0.000838	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May act as Rab effector protein and play a role in vesicle trafficking.
• Pathway: Deregulation of Rab and Rab Effector Genes in Bladder Cancer (Consensus)

Recessive Scores

• pRec: 0.0918

Intolerance Scores

• loftool: 0.971
• rvis_EVS: 4.12
• rvis_percentile_EVS: 99.69

Haploinsufficiency Scores

• pHI: 0.0962
• hipred: N
• hipred_score: 0.123
• ghis: 0.473

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.661

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Exph5

Gene ontology

• Biological process: keratinocyte development;intracellular protein transport;positive regulation of exocytosis;positive regulation of protein secretion;multivesicular body sorting pathway
• Cellular component: endosome
• Molecular function: Rab GTPase binding