EXOC4

protein-coding

exocyst complex component 4, the group of Exocyst complex|MicroRNA protein coding host genes

Gene summary

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]

Previous symbols:

SEC8L1

MANE transcript

NM_021807.4

Inheritance

—

ClinVar variants

P:1U:152B:9

Top phenotype

Polymerase proofreading-related adenomatous polyposis

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr7:133,253,072-134,067,137

External References & Databases

Ensembl (ENSG00000131558)

Transcript & Mutation Effects

hg38 • Region Span ~814.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EXOC4 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 145

not providedTotal: 7

Polymerase proofreading-related adenomatous polyposisTotal: 4

Familial colorectal cancer type XTotal: 4

Facial dysmorphism-immunodeficiency-livedo-short stature syndromeTotal: 1

Meckel-Gruber syndromeTotal: 1

Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiencyTotal: 1

Colorectal cancer, susceptibility to, 12Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021807.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar	3 clinvar	5
missense		1 clinvar	146 clinvar	3 clinvar	1 clinvar	151
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	1	152	5	4	162

Highest pathogenic variant AF is 0.00000687068

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021807.4	RefSeq	NP_068579.3	18	MANE Select
ENST00000253861.5	Ensembl	ENSP00000253861.4	18	MANE Select
NM_001037126.2	RefSeq	NP_001032203.1	10	Standard
ENST00000393161.6	Ensembl	ENSP00000376868.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Arf6 trafficking events
VxPx cargo-targeting to cilium
Stabilization and expansion of the E-cadherin adherens junction
Insulin Pathway
Cargo trafficking to the periciliary membrane

Biological Process

protein targeting to membrane
exocytosis
Golgi to plasma membrane transport
vesicle docking involved in exocytosis
chemical synaptic transmission

Molecular Function

protein binding
Ral GTPase binding
PDZ domain binding
protein N-terminus binding

Cellular Component

exocyst
cytoplasm
cytosol
plasma membrane
microvillus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000253861
Coding exons: 18
Length: 813514
Individuals with no LoFs: 125683
Homozygous LoFs: 0
Heterozygous LoFs: 65
Defined: 125748
p: 0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.516	505	539	0.937	0.0000291	6431
Missense (PolyPhen)		124	153.95	0.80544		1945
Synonymous	-0.162	210	207	1.01	0.0000115	1864
Loss of Function	2.70	28	48.3	0.580	0.00000267	559

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00056	0.00055	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.00022	0.00022	rare
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.00029	0.00029	rare
South Asian	0.00030	0.00029	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.0710
RVIS EVS: -1.28
RVIS percentile EVS: 5.17

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.860

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium