EXOC4

Chr 7

exocyst complex component 4

Also known as: SEC8, SEC8L1, Sec8p

NCBI Gene: 60412ENSG00000131558UniProt: Q96A65

The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to specific docking sites on the plasma membrane. Though best characterized in yeast, the component proteins and functions of exocyst complex have been demonstrated to be highly conserved in higher eukaryotes. At least eight components of the exocyst complex, including this protein, are found to interact with the actin cytoskeletal remodeling and vesicle transport machinery. The complex is also essential for the biogenesis of epithelial cell surface polarity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

229
ClinVar variants
33
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EXOC4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 179 VUS of 229 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.000
Z-score 2.70
OE 0.58 (0.43–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.52Z-score
OE missense 0.94 (0.87–1.01)
505 obs / 538.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.58 (0.43–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.87–1.01)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 28 / 48.3Missense obs/exp: 505 / 538.7Syn Z: -0.16

ClinVar Variant Classifications

229 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic2
VUS179
Likely Benign13
Benign4
31
Pathogenic
2
Likely Pathogenic
179
VUS
13
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
1
1
0
2
VUS
0
142
37
0
179
Likely Benign
0
3
8
2
13
Benign
0
1
0
3
4
Total0147775229

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

View in ClinVar →

Protein Context — Lollipop Plot

EXOC4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Altered methylation pattern in EXOC4 is associated with stroke outcome: an epigenome-wide association study.
Cullell N et al.·Clin Epigenetics
2022Meta-analysis
EXOC4 Promotes Diffuse-Type Gastric Cancer Metastasis via Activating FAK Signal.
Li H et al.·Mol Cancer Res
2022
Polymorphisms near EXOC4 and LRGUK on chromosome 7q32 are associated with Type 2 Diabetes and fasting glucose; the NHLBI Family Heart Study.
Laramie JM et al.·BMC Med Genet
2008
Assessing non-Mendelian inheritance in inherited axonopathies.
Bis-Brewer DM et al.·Genet Med
2020
Cancer cells resist antibody-mediated destruction by neutrophils through activation of the exocyst complex.
van Rees DJ et al.·J Immunother Cancer
2022
The contribution of 7q33 copy number variations for intellectual disability.
Lopes F et al.·Neurogenetics
2018
Distinct genetic alterations in colorectal cancer.
Ashktorab H et al.·PLoS One
2010
Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy.
Asai Y et al.·J Allergy Clin Immunol
2018Meta-analysis
Genetic variations in TP53 binding sites are predictors of clinical outcomes in prostate cancer patients.
Lin VC et al.·Arch Toxicol
2014Cohort
Mechanisms regulating cell membrane localization of the chemokine receptor CXCR4 in human hepatocarcinoma cells.
Cepeda EB et al.·Biochim Biophys Acta
2015Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools