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.

• Inborn_genetic_diseases (266 variants)
• not_provided (113 variants)
• EXPH5-related_disorder (38 variants)
• Epidermolysis_bullosa_simplex_4,_localized_or_generalized_intermediate,_autosomal_recessive (17 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. These statistics are base on transcript: NM_000015065.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				25	13	38
missense			255	38	22	315
nonsense	4	2	2			8
start loss						0
frameshift	8	3	1			12
splice donor/acceptor (+/-2bp)						0
Total	12	5	258	63	35

Highest pathogenic variant AF is 0.0000639049

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