SEC31A

Summary

SEC31A (SEC31 homolog A, COPII component, HGNC:17052) is a protein-coding gene on chromosome 4q21.22, encoding Protein transport protein Sec31A (O94979). Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).

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.

Source: NCBI Gene 22872 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies (Moderate, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 235 total — 1 pathogenic
• Phenotypes (HPO): 32
• MANE Select transcript: NM_001077207

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17052
Approved symbol	SEC31A
Name	SEC31 homolog A, COPII component
Location	4q21.22
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0905, ABP125, ABP130
Ensembl gene	ENSG00000138674
Ensembl biotype	protein_coding
OMIM	610257
Entrez	22872

Gene structure

Transcript identifiers

Ensembl transcripts: 109 — 96 protein_coding, 6 retained_intron, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000264405, ENST00000311785, ENST00000348405, ENST00000355196, ENST00000395310, ENST00000436790, ENST00000443462, ENST00000448323, ENST00000500777, ENST00000503058, ENST00000503210, ENST00000503226, ENST00000503937, ENST00000505434, ENST00000505472, ENST00000505479, ENST00000505984, ENST00000506495, ENST00000506497, ENST00000507051, ENST00000507340, ENST00000507676, ENST00000507816, ENST00000507828, ENST00000507867, ENST00000508479, ENST00000508502, ENST00000509142, ENST00000509691, ENST00000510167, ENST00000510310, ENST00000511338, ENST00000511975, ENST00000512664, ENST00000512732, ENST00000513323, ENST00000513858, ENST00000514326, ENST00000514362, ENST00000515062, ENST00000515749, ENST00000854377, ENST00000854378, ENST00000854379, ENST00000854380, ENST00000854381, ENST00000854382, ENST00000854383, ENST00000854384, ENST00000854385, ENST00000854386, ENST00000854387, ENST00000854388, ENST00000854389, ENST00000854390, ENST00000854391, ENST00000854392, ENST00000854393, ENST00000854394, ENST00000854395, ENST00000854396, ENST00000854397, ENST00000854398, ENST00000854399, ENST00000854400, ENST00000854401, ENST00000854402, ENST00000854403, ENST00000854404, ENST00000854405, ENST00000854406, ENST00000854407, ENST00000854408, ENST00000854409, ENST00000854410, ENST00000854411, ENST00000854412, ENST00000854413, ENST00000922801, ENST00000922802, ENST00000922803, ENST00000922804, ENST00000922805, ENST00000922806, ENST00000922807, ENST00000922808, ENST00000922809, ENST00000951354, ENST00000951355, ENST00000951356, ENST00000951357, ENST00000951358, ENST00000951359, ENST00000951360, ENST00000951361, ENST00000951362, ENST00000951363, ENST00000951364, ENST00000951365, ENST00000951366, ENST00000951367, ENST00000951368, ENST00000951369, ENST00000951370, ENST00000951371, ENST00000951372, ENST00000951373, ENST00000951374, ENST00000951375

RefSeq mRNA: 57 — MANE Select: NM_001077207 NM_001077206, NM_001077207, NM_001077208, NM_001191049, NM_001300744, NM_001300745, NM_001318119, NM_001318120, NM_001400154, NM_001400155, NM_001400156, NM_001400157, NM_001400158, NM_001400159, NM_001400160, NM_001400161, NM_001400162, NM_001400164, NM_001400165, NM_001400166, NM_001400167, NM_001400168, NM_001400180, NM_001400184, NM_001400186, NM_001400188, NM_001400190, NM_001400191, NM_001400193, NM_001400194, NM_001400197, NM_001400198, NM_001400200, NM_001400202, NM_001400203, NM_001400204, NM_001400205, NM_001400206, NM_001400207, NM_001400208, NM_001400209, NM_001400210, NM_001400211, NM_001400212, NM_001400213, NM_001400214, NM_001400215, NM_001400216, NM_001400217, NM_001400218, NM_001400219, NM_001400220, NM_001400221, NM_001400222, NM_001400223, NM_001400224, NM_016211

CCDS: CCDS3596, CCDS3597, CCDS43244, CCDS47088, CCDS54773, CCDS75155, CCDS75156, CCDS93555

Canonical transcript exons

ENST00000395310 — 27 exons

Exon	Start	End
ENSE00001152295	82827369	82827632
ENSE00001363731	82842140	82842481
ENSE00001592102	82844386	82844509
ENSE00001663527	82821037	82821108
ENSE00001665580	82824555	82824674
ENSE00001676179	82854903	82855029
ENSE00001694359	82861631	82861708
ENSE00001694541	82851431	82851604
ENSE00001710862	82862534	82862572
ENSE00001726089	82853570	82853715
ENSE00001754615	82863318	82863392
ENSE00001763782	82848804	82848977
ENSE00002072504	82891088	82891153
ENSE00003464644	82871944	82872086
ENSE00003472286	82829000	82829058
ENSE00003491792	82878730	82878928
ENSE00003497698	82856952	82857130
ENSE00003502331	82874611	82874751
ENSE00003506262	82870325	82870424
ENSE00003508558	82857689	82857764
ENSE00003532459	82864362	82864598
ENSE00003555851	82866808	82866960
ENSE00003575805	82867155	82867316
ENSE00003661793	82880799	82880922
ENSE00003699314	82881858	82881940
ENSE00003790022	82875727	82875822
ENSE00003849677	82818509	82819253

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 76.8138 / max 1130.1496, expressed in 1826 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52894	72.2859	1825
52897	15.0376	1733
52885	1.3466	829
52888	0.8803	591
52895	0.6548	397
52887	0.5181	306
52886	0.4081	194
52893	0.3020	133
52884	0.2879	54
52892	0.1301	42

Top tissues by expression

303 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.10	gold quality
pancreatic ductal cell	CL:0002079	99.09	gold quality
body of pancreas	UBERON:0001150	99.08	gold quality
tibia	UBERON:0000979	99.05	gold quality
calcaneal tendon	UBERON:0003701	99.03	gold quality
stromal cell of endometrium	CL:0002255	98.85	gold quality
colonic epithelium	UBERON:0000397	98.83	gold quality
pancreas	UBERON:0001264	98.78	gold quality
periodontal ligament	UBERON:0008266	98.77	gold quality
right ovary	UBERON:0002118	98.74	gold quality
left ovary	UBERON:0002119	98.74	gold quality
cartilage tissue	UBERON:0002418	98.68	gold quality
islet of Langerhans	UBERON:0000006	98.63	gold quality
blood vessel layer	UBERON:0004797	98.60	gold quality
synovial joint	UBERON:0002217	98.59	gold quality
endocervix	UBERON:0000458	98.54	gold quality
skin of hip	UBERON:0001554	98.54	gold quality
cauda epididymis	UBERON:0004360	98.53	gold quality
pituitary gland	UBERON:0000007	98.51	gold quality
decidua	UBERON:0002450	98.47	gold quality
adrenal tissue	UBERON:0018303	98.47	gold quality
caput epididymis	UBERON:0004358	98.45	gold quality
ascending aorta	UBERON:0001496	98.44	gold quality
endometrium	UBERON:0001295	98.43	gold quality
thoracic aorta	UBERON:0001515	98.43	gold quality
myometrium	UBERON:0001296	98.41	gold quality
smooth muscle tissue	UBERON:0001135	98.38	gold quality
seminal vesicle	UBERON:0000998	98.37	gold quality
pylorus	UBERON:0001166	98.37	gold quality
adenohypophysis	UBERON:0002196	98.36	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ENAD-21	no	1339.63
E-GEOD-75367	no	609.48
E-MTAB-2983	no	308.48
E-GEOD-93593	no	7.58
E-CURD-112	no	2.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting SEC31A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-4291	99.20	68.88	2969

Literature-anchored findings (GeneRIF, showing 18)

• Genomic PCR and subsequent sequencing showed that the breakpoints were located in intron 23 of SEC31L1 and intron 20 of anaplastic lymphoma kinase (PMID:16161041)
• three-dimensional reconstruction of Sec13/31 cages at 30 A resolution using cryo-electron microscopy and single particle analysis (PMID:16407955)
• ALG-2 is recruited to endoplasmic reticulum exit sites via Ca(2+)-dependent interaction with Sec31A and in turn stabilizes the localization of Sec31A at these sites. (PMID:16957052)
• In vitro GST pull down analysis demonstrated that ALG-2 and its alternatively spliced isoform interact with the COPII component Sec31A in a Ca2+-dependent manner, and a biotin-labeled ALG-2 overlay assay revealed direct binding of ALG-2 to Sec31A. (PMID:17196169)
• The Sec31 active fragment is accommodated in a binding groove supported in part by Sec23 residue Phe380. (PMID:17981133)
• Data show that coupling of the Sec23/24 and Sec13/31 layers of the COPII coat is required to drive export of collagen from the endoplasmic reticulum, and that efficient COPII assembly is essential for normal craniofacial development during embryogenesis. (PMID:18713835)
• the alg2 binding site is one of the key determinants of the retention kinetics of Sec31A at endoplasmic reticulum exit sites (PMID:20834162)
• SEC31A-ALK fusions are recurrent in ALK-positive large B-cell lymphomas. (PMID:21109691)
• t(4;9)(q21;p24) leads to a novel SEC31A-JAK2 fusion in Hodgkin lymphoma (PMID:21325169)
• efficient COPII-dependent secretion, notably assembly of Sec13-Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures (PMID:22331354)
• These results suggest that Sec31 phosphorylation by CK2 controls the duration of COPII vesicle formation, which regulates ER-to-Golgi trafficking. (PMID:23349870)
• ALG-2 attenuates COPII budding in vitro and stabilizes the Sec23/Sec31A complex. (PMID:24069399)
• ALG-2/Sec31A interactions were not required for the localization of Sec31A to ER exit sites per se but appeared to acutely regulate the stability and trafficking of the cargo receptor p24 and the distribution of the vesicle tether protein p115 (PMID:25006245)
• findings suggest that AnxA11 maintains architectural and functional features of the ERES by coordinating with ALG-2 to stabilize Sec31A at the ERES. (PMID:25540196)
• Results show the crystal structure of the complex between ALG-2 and a peptide of Sec31A and found that the peptide binds to the third hydrophobic pocket (Pocket 3) and that ALG-2 recognizing 2 types of motifs at different hydrophobic surfaces of Sec31A. (PMID:25667979)
• USP8 deubiquitinates Sec31A and inhibits the formation of large COPII carriers, thereby suppressing collagen IV secretion. (PMID:29604273)
• We demonstrate through human and Drosophila genetic and in vitro molecular studies, that a severe neurological syndrome is caused by a null mutation in SEC31A, reducing cell viability through enhanced ER-stress response, in line with SEC31A’s role in the COP-II complex. (PMID:30464055)
• SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. (PMID:38400880)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sec31a	ENSDARG00000021082
mus_musculus	Sec31a	ENSMUSG00000035325
rattus_norvegicus	Sec31a	ENSRNOG00000002251
drosophila_melanogaster	Sec31	FBGN0033339
caenorhabditis_elegans		WBGENE00011338

Paralogs (1): SEC31B (ENSG00000075826)

Protein

Protein identifiers

Protein transport protein Sec31A — O94979 (reviewed: O94979)

Alternative names: ABP125, ABP130, SEC31-like protein 1, SEC31-related protein A, Web1-like protein

All UniProt accessions (20): O94979, D6RAB3, D6RBT0, D6RCQ9, D6RE64, D6REA9, D6REC0, D6REX3, D6RHE8, D6RHZ5, H0Y8V7, H0Y8W8, H0Y9K1, H0Y9T9, H0Y9V3, H0YAB3, H0YAF5, H7BXG7, U3KQC9, U3KQR3

UniProt curated annotations — full annotation on UniProt →

Function. Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules.

Subunit / interactions. COPII is composed of at least 5 proteins: the SEC23/24 complex, the SEC13/31 complex and SAR1. SEC13 and SEC31 make a 2:2 tetramer that forms the edge element of the COPII outer coat. The tetramer self-assembles in multiple copies to form the complete polyhedral cage. Interacts (via WD 8) with SEC13. Interacts with PDCD6; interaction takes place in response to cytosolic calcium increase and leads to bridge together the BCR(KLHL12) complex and SEC31A, leading to monoubiquitination. Interacts with KLHL12.

Subcellular location. Cytoplasm. Cytoplasmic vesicle. COPII-coated vesicle membrane. Endoplasmic reticulum membrane. Cytosol.

Tissue specificity. Abundantly and ubiquitously expressed.

Post-translational modifications. Monoubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex, leading to regulate the size of COPII coats.

Disease relevance. Halperin-Birk syndrome (HLBKS) [MIM:618651] An autosomal recessive, congenital neurodevelopmental disorder characterized by intrauterine growth retardation, microcephaly, marked developmental delay, spastic quadriplegia with profound contractures, pseudobulbar palsy with recurrent aspirations, epilepsy, dysmorphism, neurosensory deafness, optic nerve atrophy with no eye fixation, and death in early childhood. Brain imaging shows semilobar holoprosencephaly and agenesis of corpus callosum. The disease may be caused by variants affecting the gene represented in this entry. A chromosomal aberration involving SEC31A is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;4)(p23;q21) with ALK.

Domain organisation. The ALG-2-binding site motif-2 (ABS-2) contains a PXPGF sequence that binds hydrophobic pocket 3 of PDCD6.

Similarity. Belongs to the WD repeat SEC31 family.

Isoforms (10)

UniProt ID	Names	Canonical?
O94979-1	1	yes
O94979-2	2
O94979-3	3
O94979-4	4
O94979-5	5
O94979-6	6
O94979-7	7
O94979-8	8
O94979-9	9
O94979-10	10

RefSeq proteins (57): NP_001070674, NP_001070675, NP_001070676, NP_001177978, NP_001287673, NP_001287674, NP_001305048, NP_001305049, NP_001387083, NP_001387084, NP_001387085, NP_001387086, NP_001387087, NP_001387088, NP_001387089, NP_001387090, NP_001387091, NP_001387093, NP_001387094, NP_001387095, NP_001387096, NP_001387097, NP_001387109, NP_001387113, NP_001387115, NP_001387117, NP_001387119, NP_001387120, NP_001387122, NP_001387123, NP_001387126, NP_001387127, NP_001387129, NP_001387131, NP_001387132, NP_001387133, NP_001387134, NP_001387135, NP_001387136, NP_001387137, NP_001387138, NP_001387139, NP_001387140, NP_001387141, NP_001387142, NP_001387143, NP_001387144, NP_001387145, NP_001387146, NP_001387147, NP_001387148, NP_001387149, NP_001387150, NP_001387151, NP_001387152, NP_001387153, NP_057295 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR024298	Sec16_Sec23-bd	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR040251	SEC31-like	Family

Pfam: PF12931

UniProt features (84 total): strand 33, splice variant 11, repeat 8, compositionally biased region 5, modified residue 5, region of interest 4, sequence variant 4, sequence conflict 4, turn 3, cross-link 2, mutagenesis site 2, chain 1, short sequence motif 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3WXA	X-RAY DIFFRACTION	2.36
7SUL	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94979-F1	68.95	0.22

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 527, 532, 799, 1161, 1163, 647, 1217

Mutagenesis-validated functional residues (2):

Position	Phenotype
647	does not abolish monoubiquitination by the bcr(klhl12) e3 ubiquitin ligase complex, revealing flexibility of ubiquitinat
1217	does not abolish monoubiquitination by the bcr(klhl12) e3 ubiquitin ligase complex, revealing flexibility of ubiquitinat

Function

Pathways and Gene Ontology

Reactome pathways

22 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-2132295	MHC class II antigen presentation
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-983170	Antigen Presentation: Folding, assembly and peptide loading of class I MHC
R-HSA-1280218	Adaptive Immune System
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-2262752	Cellular responses to stress
R-HSA-381070	IRE1alpha activates chaperones
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-597592	Post-translational protein modification
R-HSA-8953897	Cellular responses to stimuli
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9700206	Signaling by ALK in cancer
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 312 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOBP_VESICLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, MORF_ATRX, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, LANG_MYB_FAMILY_TARGETS, MODULE_264, CAFFAREL_RESPONSE_TO_THC_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING

GO Biological Process (6): endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), endoplasmic reticulum organization (GO:0007029), protein transport (GO:0015031), response to calcium ion (GO:0051592), COPII-coated vesicle cargo loading (GO:0090110), vesicle-mediated transport (GO:0016192)

GO Molecular Function (3): structural molecule activity (GO:0005198), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515)

GO Cellular Component (13): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), ER to Golgi transport vesicle membrane (GO:0012507), vesicle coat (GO:0030120), COPII vesicle coat (GO:0030127), COPII-coated ER to Golgi transport vesicle (GO:0030134), perinuclear region of cytoplasm (GO:0048471), endoplasmic reticulum exit site (GO:0070971), endomembrane system (GO:0012505), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	1
Adaptive Immune System	1
IRE1alpha activates chaperones	1
Signaling by ALK in cancer	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Cellular responses to stimuli	1
Unfolded Protein Response (UPR)	1
Cellular responses to stress	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	5
intracellular transport	2
transport	2
coated vesicle membrane	2
intercellular transport	1
Golgi vesicle transport	1
organelle organization	1
endomembrane system organization	1
intracellular protein localization	1
establishment of protein localization	1
response to metal ion	1
vesicle cargo loading	1
COPII-coated vesicle budding	1
cellular process	1
molecular_function	1
calcium ion binding	1
protein binding	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
COPII-coated ER to Golgi transport vesicle	1
transport vesicle membrane	1
membrane coat	1
ER to Golgi transport vesicle membrane	1
vesicle coat	1
coated vesicle	1
endoplasmic reticulum	1
vacuole	1
plasma membrane	1
intracellular vesicle	1

Protein interactions and networks

STRING

1624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEC31A	SEC13	P55735	990
SEC31A	SEC23A	Q15436	979
SEC31A	SEC24B	O95487	933
SEC31A	SEC16A	O15027	932
SEC31A	SAR1A	Q9NR31	929
SEC31A	SEC24C	P53992	914
SEC31A	PREB	Q9HCU5	895
SEC31A	LMAN1	P49257	893
SEC31A	SEC24D	O94855	892
SEC31A	SEC24A	O95486	888
SEC31A	SAR1B	Q9Y6B6	882
SEC31A	SEC16B	Q96JE7	838
SEC31A	PDCD6	O75340	820
SEC31A	GOLPH3	Q9H4A6	805
SEC31A	SEC23B	Q15437	801

IntAct

120 interactions, top by confidence:

A	B	Type	Score
PDCD6	SEC31A	psi-mi:“MI:0403”(colocalization)	0.740
SEC31A	PDCD6	psi-mi:“MI:0915”(physical association)	0.740
SEC31A	PDCD6	psi-mi:“MI:0403”(colocalization)	0.740
PDCD6	SEC31A	psi-mi:“MI:0915”(physical association)	0.740
PDCD6	SEC31A	psi-mi:“MI:0914”(association)	0.740
SEC31A	SEC13	psi-mi:“MI:0407”(direct interaction)	0.730
SEC31A	SEC13	psi-mi:“MI:0914”(association)	0.730
SEC31A	SEC13	psi-mi:“MI:0915”(physical association)	0.730
SCYL1	SEC31A	psi-mi:“MI:0914”(association)	0.710
SCYL1	SEC31A	psi-mi:“MI:0915”(physical association)	0.710
SPTLC1	SPTLC2	psi-mi:“MI:0914”(association)	0.680
POLR1E	POLR1C	psi-mi:“MI:0914”(association)	0.670
SEC13	SEC16A	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
REL	SEC31A	psi-mi:“MI:0915”(physical association)	0.560
SEC31A	REL	psi-mi:“MI:0915”(physical association)	0.560
SEC31A	NOP14	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
SEC23A	SEC31A	psi-mi:“MI:0407”(direct interaction)	0.510
SEC23A	SEC31A	psi-mi:“MI:0915”(physical association)	0.510
SEC31A	PPP1CA	psi-mi:“MI:0915”(physical association)	0.400
SEC31A	LUZP1	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
SEC31A	TSC1	psi-mi:“MI:0915”(physical association)	0.370
SEC31A	PFDN1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (345): SEC31A (Two-hybrid), SEC31A (Affinity Capture-RNA), SEC31A (Affinity Capture-RNA), SEC31A (Affinity Capture-RNA), SEC31A (Affinity Capture-MS), SEC31A (Affinity Capture-MS), SEC31A (Affinity Capture-MS), C6orf211 (Co-fractionation), ATP6V1C1 (Co-fractionation), ENO2 (Co-fractionation), FDPS (Co-fractionation), NUDT13 (Co-fractionation), SEC13 (Co-fractionation), SEC23A (Co-fractionation), SEC23B (Co-fractionation)

ESM2 similar proteins: A1C6X5, A1DHK2, A2QBZ0, A3GFK8, A4RD35, A5DB75, A5DTX3, F4ICD9, G0S7B6, O13637, O74965, O94979, P38968, Q0CQ54, Q0CVT0, Q0CYG9, Q0ULF5, Q0UNC6, Q1DHE1, Q1DX43, Q2GSJ9, Q2GVT8, Q2H401, Q2KFH6, Q2UBU2, Q2UF60, Q3UPL0, Q4IBR4, Q4IR09, Q4P2B6, Q4WTC4, Q4X0M4, Q5AAU3, Q5AZM3, Q5BDU4, Q5F3X8, Q5R4F4, Q5S580, Q6BRR2, Q6C414

Diamond homologs: A1C6X5, A1DHK2, A2QBZ0, A3GFK8, A4RD35, A5DB75, A5DTX3, I7MM07, O13637, O94979, Q0CYG9, Q0ULF5, Q1DX43, Q2GVT8, Q2UF60, Q3UPL0, Q4P2B6, Q4X0M4, Q5AAU3, Q5AZM3, Q5F3X8, Q5R4F4, Q5S580, Q6BRR2, Q6C414, Q7SYD5, Q873A1, Q8L611, Q9Z2Q1, Q6QGW5, C5MIB1, F4ICD9, Q21624, Q4WEI5, Q9FND4, Q3TZ89, Q55CT5, Q9NQW1, Q6FNU4, Q9HD15

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SEC31A	“form complex”	“COPII vesicle”	binding
KLHL12	“up-regulates activity”	SEC31A	binding
“Cullin 3-RBX1-Skp1”	“up-regulates activity”	SEC31A	monoubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
COPII-mediated vesicle transport	6	13.6×	3e-03
Constitutive Signaling by Aberrant PI3K in Cancer	6	10.6×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	7	33.1×	2e-06
cell surface receptor protein tyrosine kinase signaling pathway	8	15.6×	2e-05
protein autophosphorylation	8	13.1×	6e-05
endoplasmic reticulum to Golgi vesicle-mediated transport	7	10.7×	1e-03
positive regulation of MAPK cascade	8	7.2×	2e-03
positive regulation of cell migration	9	6.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

235 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	153
Likely benign	18
Benign	10

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
694295	NM_001077207.4(SEC31A):c.2776_2777dup (p.Ala927fs)	Pathogenic

SpliceAI

4076 predictions. Top by Δscore:

Variant	Effect	Δscore
4:82819253:GCTGA:G	acceptor_loss	1.0000
4:82819254:C:T	acceptor_loss	1.0000
4:82821030:AACTT:A	donor_loss	1.0000
4:82821031:ACTT:A	donor_loss	1.0000
4:82821032:CTTAC:C	donor_loss	1.0000
4:82821033:TTA:T	donor_loss	1.0000
4:82821034:TA:T	donor_loss	1.0000
4:82821035:A:AC	donor_gain	1.0000
4:82821036:C:CG	donor_gain	1.0000
4:82821036:CT:C	donor_gain	1.0000
4:82821036:CTG:C	donor_gain	1.0000
4:82821036:CTGT:C	donor_gain	1.0000
4:82821104:GTTTG:G	acceptor_gain	1.0000
4:82821105:TTTG:T	acceptor_gain	1.0000
4:82821106:TTG:T	acceptor_gain	1.0000
4:82821106:TTGCT:T	acceptor_loss	1.0000
4:82821107:TG:T	acceptor_gain	1.0000
4:82821108:GCTGC:G	acceptor_loss	1.0000
4:82821109:C:CC	acceptor_gain	1.0000
4:82821109:CTGCA:C	acceptor_loss	1.0000
4:82821110:T:A	acceptor_loss	1.0000
4:82821113:A:T	acceptor_gain	1.0000
4:82824549:ACAT:A	donor_loss	1.0000
4:82824551:ATAC:A	donor_loss	1.0000
4:82824552:TA:T	donor_loss	1.0000
4:82824553:A:AC	donor_gain	1.0000
4:82824554:C:CC	donor_gain	1.0000
4:82824554:CAGG:C	donor_gain	1.0000
4:82824554:CAGGG:C	donor_gain	1.0000
4:82824671:CATG:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000600 (4:82883839 A>G), RS1000019032 (4:82900290 T>C), RS1000151280 (4:82841347 C>T), RS1000154176 (4:82899867 A>C), RS1000156313 (4:82855568 A>C), RS1000208811 (4:82890766 G>C,T), RS1000209162 (4:82839134 G>A), RS1000213393 (4:82836174 A>C), RS1000268128 (4:82893710 AAGG>A), RS1000268173 (4:82827844 G>A), RS1000269249 (4:82846153 G>A,T), RS1000274931 (4:82846863 C>T), RS1000312683 (4:82887684 G>A), RS10003418 (4:82822040 T>C), RS1000365750 (4:82842482 C>A,T)

Disease associations

OMIM: gene MIM:610257 | disease phenotypes: MIM:619125, MIM:618651

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies	Moderate	Autosomal recessive

Mondo (2): Kaya-Barakat-Masson syndrome (MONDO:0030878), neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies (MONDO:0032849)

Orphanet (1): Neurodevelopmental disorder-spasticity-movement disorder-epileptic syndrome (Orphanet:684240)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000218	High palate
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000519	Developmental cataract
HP:0000527	Long eyelashes
HP:0000648	Optic atrophy
HP:0000776	Congenital diaphragmatic hernia
HP:0001274	Agenesis of corpus callosum
HP:0001276	Hypertonia
HP:0001347	Hyperreflexia
HP:0001371	Flexion contracture
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001537	Umbilical hernia
HP:0001762	Talipes equinovarus
HP:0002020	Gastroesophageal reflux
HP:0002119	Ventriculomegaly
HP:0002197	Generalized-onset seizure
HP:0002507	Semilobar holoprosencephaly
HP:0002510	Spastic tetraplegia
HP:0002540	Inability to walk
HP:0002827	Hip dislocation
HP:0002835	Aspiration
HP:0003819	Death in childhood
HP:0007024	Pseudobulbar paralysis
HP:0007359	Focal-onset seizure
HP:0011682	Perimembranous ventricular septal defect

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003833_15	Adult asthma	3.000000e-06
GCST004633_49	Neutrophil percentage of white cells	8.000000e-09
GCST012490_100	Femur bone mineral density x serum urate levels interaction	9.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

71 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	4
bisphenol A	increases expression, decreases expression	3
sodium arsenite	affects expression, decreases expression, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Cisplatin	increases expression, decreases expression, affects cotreatment	2
Lead	affects splicing, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	affects sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	increases expression	1
coumarin	increases phosphorylation	1
tamibarotene	decreases expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	increases secretion, affects cotreatment	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
bisphenol S	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_XS54	HAP1 SEC31A (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.