EXOC7

protein-coding

exocyst complex component 7, 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. The exocyst complex plays a critical role in vesicular trafficking and the secretory pathway by targeting post-Golgi vesicles to the plasma membrane. The encoded protein is required for assembly of the exocyst complex and docking of the complex to the plasma membrane. The encoded protein may also play a role in pre-mRNA splicing through interactions with pre-mRNA-processing factor 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Nov 2011]

MANE transcript

NM_001013839.4

Inheritance

ClinVar variants

P:3U:104B:19

Top phenotype

neurodevelopmental disorder with seizures and brain atrophy

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr17:76,081,016-76,121,576

External References & Databases

Ensembl (ENSG00000182473)

Transcript & Mutation Effects

hg38 • Region Span ~40.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with seizures and brain atrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033658

Submitter: PanelApp Australia

neurodevelopmental disorder with seizures and brain atrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033658

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with seizures and brain atrophyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0033658

Submitter: ClinGen

*EXOC7* encodes a component of the exocyst complex that mediates fusion of intracellular vesicles to the plasma membrane during exocytosis and is highly expressed in the developing human cortex. *EXOC7* was first reported in relation to autosomal recessive neurodevelopmental disorder with seizures and brain atrophy in 2020 (Coulter et al., PMID: 32103185). The disorder is characterized by developmental delay, seizures, and brain atrophy, and in more severe cases, microcephaly and infantile death. Four variants (1 splice, 2 in-frame deletions, and 1 missense) reported in four probands in one publication (PMID: 32103185) are included in this curation. However, only the splice variant, identified in two families in homozygosity or compound heterozygosity, has supportive functional evidence and was scored at full points. The mechanism of pathogenicity is suggested to be partial loss of function (PMID: 32103185) but functional characterization of the missense and in-frame variants is necessary to elucidate the disease mechanism. This gene-disease relationship is also supported by a null zebrafish model that recapitulates the human disorder with microcephaly, increased apoptosis and decreased progenitor cells in the developing telencephalon, suggesting that the brain atrophy in patients reflects neuronal degeneration (PMID: 32103185). Of note, homozygous truncating variants in another member of the exocyst complex, *EXOC8*, have been reported in two unrelated families with a similar clinical disorder involving microcephaly, seizures, and brain atrophy (PMIDs: 32103185, 35460391). In summary, there is moderate evidence supporting the relationship between *EXOC7* and autosomal recessive neurodevelopmental disorder with seizures and brain atrophy. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This gene-disease pair was originally evaluated by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on June 20, 2023. It was reevaluated on October 1, 2026. As a result of this reevaluation, no additional patients were identified, and the classification did not change. The scoring was updated to be consistent with SOP Version 12.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EXOC7 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 99

not providedTotal: 21

Neurodevelopmental disorder with seizures and brain atrophyTotal: 16

EXOC7-related disorderTotal: 2

See casesTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001013839.4. 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			1 clinvar	11 clinvar	1 clinvar	13
missense	1 clinvar		92 clinvar	6 clinvar	1 clinvar	100
nonsense	1 clinvar		2 clinvar			3
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar		8 clinvar			9
Total	3	0	104	17	2	126

Highest pathogenic variant AF is 0.000035335164

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001013839.4	RefSeq	NP_001013861.1	19	MANE Select
ENST00000589210.6	Ensembl	ENSP00000468404.1	19	MANE Select
NM_001145297.4	RefSeq	NP_001138769.1	20	Standard
NM_001145298.4	RefSeq	NP_001138770.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Insulin signaling pathway - Homo sapiens (human)
Angiopoietin Like Protein 8 Regulatory Pathway
Arf6 trafficking events
VxPx cargo-targeting to cilium
Insulin Pathway

Biological Process

exocytosis
protein transport
regulation of macroautophagy
regulation of entry of bacterium into host cell

Molecular Function

protein binding

Cellular Component

exocyst
microtubule organizing center
cytosol
plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000335146
Coding exons: 20
Length: 40571
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125748
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.88	344	457	0.753	0.0000284	4846
Missense (PolyPhen)		83	136.23	0.60925		1618
Synonymous	1.05	176	195	0.904	0.0000135	1401
Loss of Function	3.32	18	41.0	0.439	0.00000201	467

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.000099	0.000098	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. In adipocytes, plays a crucial role in targeting SLC2A4 vesicle to the plasma membrane in response to insulin, perhaps directing the vesicle to the precise site of fusion (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.176

Intolerance Scores

LoFtool: 0.0265
RVIS EVS: -0.93
RVIS percentile EVS: 9.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.687

Gene Damage Prediction

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