EXOC8

Chr 1AR

exocyst complex component 8

Also known as: EXO84, Exo84p, NEDMISB, SEC84

NCBI Gene: 149371 ENSG00000116903 UniProt: Q8IYI6 OMIM: 615283

The protein is a component of the exocyst complex that docks exocytic vesicles to the plasma membrane for secretion. Mutations cause a neurodevelopmental disorder with microcephaly, seizures, and brain atrophy, inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function variants, indicating intolerance to protein disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a component of the exocyst complex, an evolutionarily conserved multi-protein complex that plays a critical role in vesicular trafficking and the secretory pathway by targeting post-Golgi vesicles to the plasma membrane. This protein is a target of activated Ral subfamily of GTPases and thereby regulates exocytosis by tethering vesicles to the plasma membrane. Mutations in this gene may be related to Joubert syndrome. [provided by RefSeq, Sep 2016]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.191 OMIM phenotype

Clinical Summary— EXOC8

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 81 VUS of 106 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 0.999

Z-score 4.40

OE 0.04 (0.01–0.19)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.04Z-score

OE missense 0.72 (0.65–0.79)

294 obs / 410.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.19)

0≤0.351.4

Missense OE?0.72 (0.65–0.79)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 1 / 24.5Missense obs/exp: 294 / 410.4Syn Z: -0.05

ClinVar Variant Classifications

106 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic2

VUS81

Likely Benign15

Benign8

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	2	0	0	0	2
VUS	2	79	0	0	81
Likely Benign	0	2	0	13	15
Benign	0	3	1	4	8
Total	4	84	1	17	106

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

View in ClinVar →

37 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap EXOC8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →