EXPH5

Chr 11

exophilin 5

Also known as: EBS4, SLAC2-B, SLAC2B

NCBI Gene: 23086 ENSG00000110723 UniProt: Q8NEV8

The protein is a Rab-27B effector involved in exosome secretion and intracellular vesicle trafficking. Mutations cause epidermolysis bullosa simplex 4, a skin fragility disorder with localized or generalized intermediate severity, inherited in an autosomal recessive pattern. The gene is not highly constrained against loss-of-function variants.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the synaptotagmin-like protein (Slp) family lacking a C2 domain. It contains an N-terminal synaptotagmin-like homology domain (SHD), and is a ras-related protein Rab-27B effector protein. This protein is thought to be involved in exosome secretion and intracellular vesicle trafficking. Reduced expression of this gene results in keratin filament defects. Mutations in this gene have been associated with some cases of epidermolysis bullosa, an inherited skin fragility disorder. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.94

Clinical Summary— EXPH5

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

16 unique Pathogenic / Likely Pathogenic· 277 VUS of 432 total submissions

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GeneReview available — EXPH5

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.000

Z-score 1.93

OE 0.74 (0.59–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.27Z-score

OE missense 1.02 (0.97–1.08)

1025 obs / 1000.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.74 (0.59–0.94)

0≤0.351.4

Missense OE?1.02 (0.97–1.08)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 49 / 65.9Missense obs/exp: 1025 / 1000.6Syn Z: 0.60

ClinVar Variant Classifications

432 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic5

VUS277

Likely Benign65

Benign53

Conflicting12

Pathogenic

Likely Pathogenic

277

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	0	0	0	11
Likely Pathogenic	5	0	0	0	5
VUS	3	274	0	0	277
Likely Benign	0	30	5	30	65
Benign	0	29	10	14	53
Conflicting	—				12
Total	19	333	15	44	423

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

17 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap EXPH5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →