SEC31A

protein-coding

SEC31 homolog A, COPII coat complex component, the group of COPII coat complex|WD repeat domain containing

Gene summary

The protein encoded by this gene shares similarity with the yeast Sec31 protein, and is a component of the outer layer of the coat protein complex II (COPII). The encoded protein is involved in vesicle budding from the endoplasmic reticulum (ER) and contains multiple WD repeats near the N-terminus and a proline-rich region in the C-terminal half. It associates with the protein encoded by the SEC13 homolog, nuclear pore and COPII coat complex component (SEC13), and is required for ER-Golgi transport. Monoubiquitylation of this protein by CUL3-KLHL12 was found to regulate the size of COPII coats to accommodate unusually shaped cargo. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

Previous symbols:

SEC31L1

MANE transcript

NM_001077207.4

Inheritance

ClinVar variants

P:1U:133B:22

Top phenotype

Halperin-Birk syndrome

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr4:82,818,509-82,901,166

External References & Databases

Ensembl (ENSG00000138674)

Transcript & Mutation Effects

hg38 • Region Span ~82.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomaliesLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0032849

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomaliesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032849

Submitter: Ambry Genetics

neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomaliesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032849

Submitter: Ambry Genetics

neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomaliesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032849

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Halperin-Birk syndromeAR

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30464055

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEC31A variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 118

not providedTotal: 23

Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomaliesTotal: 3

SEC31A-related disorderTotal: 3

Kaya-Barakat-Masson syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001077207.4. 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			3 clinvar	14 clinvar	1 clinvar	18
missense			120 clinvar	3 clinvar	3 clinvar	126
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)			8 clinvar	1 clinvar		9
Total	1	0	133	18	4	156

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 259 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001077207.4	RefSeq	NP_001070675.1	26	MANE Select
ENST00000395310.7	Ensembl	ENSP00000378721.2	26	MANE Select
NM_001077206.4	RefSeq	NP_001070674.1	25	Standard
NM_001077208.4	RefSeq	NP_001070676.1	26	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sec31a	Danio rerio	Structure: endodermal cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

sec31a

Danio rerio

Structure: endodermal cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein processing in endoplasmic reticulum - Homo sapiens (human)
Sterol Regulatory Element-Binding Proteins (SREBP) signalling
XBP1(S) activates chaperone genes
Vesicle-mediated transport
Membrane Trafficking

Biological Process

antigen processing and presentation of peptide antigen via MHC class I
intracellular protein transport
endoplasmic reticulum to Golgi vesicle-mediated transport
endoplasmic reticulum organization
antigen processing and presentation of exogenous peptide antigen via MHC class II

Molecular Function

structural molecule activity
protein binding
calcium-dependent protein binding

Cellular Component

Golgi membrane
cytoplasm
endoplasmic reticulum
endoplasmic reticulum membrane
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395310
Coding exons: 26
Length: 82506
Individuals with no LoFs: 125528
Homozygous LoFs: 1
Heterozygous LoFs: 218
Defined: 125747
p: 0.000871

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.23	559	647	0.864	0.0000320	7945
Missense (PolyPhen)		127	177.4	0.71591		2240
Synonymous	-0.614	240	228	1.05	0.0000118	2390
Loss of Function	5.35	21	68.9	0.305	0.00000363	775

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0080	0.0077	notable
Latino/Admixed American	0.0015	0.0013	notable
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00033	0.00031	rare
South Asian	0.000033	0.000033	rare
Other	0.0022	0.0018	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER) (PubMed:10788476). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules (By similarity). {ECO:0000250|UniProtKB:Q9Z2Q1, ECO:0000269|PubMed:10788476}.;
Disease: DISEASE: Note=A chromosomal aberration involving SEC31A is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;4)(p23;q21) with ALK.;

Recessive Scores

pRec: 0.136

Intolerance Scores

LoFtool: 0.787
RVIS EVS: -0.99
RVIS percentile EVS: 8.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.913

Gene Damage Prediction

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