SEC24A

Summary

SEC24A (SEC24 homolog A, COPII component, HGNC:10703) is a protein-coding gene on chromosome 5q31.1, encoding Protein transport protein Sec24A (O95486). 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 belongs to a family of proteins that are homologous to yeast Sec24. This protein is a component of coat protein II (COPII)-coated vesicles that mediate protein transport from the endoplasmic reticulum. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the golgi complex. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10802 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 179 total
• MANE Select transcript: NM_021982

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10703
Approved symbol	SEC24A
Name	SEC24 homolog A, COPII component
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000113615
Ensembl biotype	protein_coding
OMIM	607183
Entrez	10802

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000322887, ENST00000398844, ENST00000513123, ENST00000903397, ENST00000903398, ENST00000939610, ENST00000939611, ENST00000939612, ENST00000939613, ENST00000939614

RefSeq mRNA: 2 — MANE Select: NM_021982 NM_001252231, NM_021982

CCDS: CCDS43363, CCDS58967

Canonical transcript exons

ENST00000398844 — 23 exons

Exon	Start	End
ENSE00000763424	134688181	134688299
ENSE00001006713	134686790	134686902
ENSE00001085918	134715024	134715161
ENSE00001085920	134703759	134703932
ENSE00001085922	134697126	134697246
ENSE00001085924	134705327	134705437
ENSE00001085927	134708713	134708888
ENSE00001085928	134724980	134727909
ENSE00001085930	134723567	134723670
ENSE00001085933	134693727	134693933
ENSE00001085934	134718069	134718173
ENSE00001085939	134720998	134721090
ENSE00001085940	134697899	134698057
ENSE00001132071	134679602	134679728
ENSE00001132074	134676023	134676125
ENSE00001132080	134675045	134675217
ENSE00001132085	134674615	134674775
ENSE00001132092	134671809	134671886
ENSE00001132099	134666823	134666996
ENSE00001264229	134661119	134661586
ENSE00001345476	134648785	134649173
ENSE00002468599	134682373	134682482
ENSE00002523604	134692602	134692657

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.7381 / max 351.3737, expressed in 1824 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58603	47.0080	1824
58604	4.0923	1510
58598	1.2522	841
58602	0.8263	518
58600	0.7446	281
58601	0.6323	273
58599	0.1601	67
58597	0.0224	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.07	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.02	gold quality
oocyte	CL:0000023	95.98	gold quality
cartilage tissue	UBERON:0002418	95.52	gold quality
parotid gland	UBERON:0001831	95.29	gold quality
colonic mucosa	UBERON:0000317	95.08	gold quality
oral cavity	UBERON:0000167	94.94	gold quality
tongue squamous epithelium	UBERON:0006919	94.89	gold quality
secondary oocyte	CL:0000655	94.79	gold quality
cervix squamous epithelium	UBERON:0006922	94.73	gold quality
choroid plexus epithelium	UBERON:0003911	94.60	gold quality
cauda epididymis	UBERON:0004360	94.57	gold quality
tibia	UBERON:0000979	94.54	gold quality
gingival epithelium	UBERON:0001949	94.48	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.16	gold quality
corpus epididymis	UBERON:0004359	94.11	gold quality
gingiva	UBERON:0001828	94.03	gold quality
trabecular bone tissue	UBERON:0002483	93.70	gold quality
caput epididymis	UBERON:0004358	93.53	gold quality
periodontal ligament	UBERON:0008266	93.29	gold quality
palpebral conjunctiva	UBERON:0001812	93.16	gold quality
pigmented layer of retina	UBERON:0001782	92.84	gold quality
buccal mucosa cell	CL:0002336	92.79	gold quality
endothelial cell	CL:0000115	92.77	gold quality
jejunum	UBERON:0002115	92.77	gold quality
squamous epithelium	UBERON:0006914	92.76	gold quality
duodenum	UBERON:0002114	92.33	gold quality
oviduct epithelium	UBERON:0004804	91.97	gold quality
cervix epithelium	UBERON:0004801	91.73	gold quality
germinal epithelium of ovary	UBERON:0001304	91.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	18.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

243 targeting SEC24A, 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-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707

Literature-anchored findings (GeneRIF, showing 6)

• Sec24 isoforms expand the repertoire of cargo for signal-mediated ER export, but are in part functionally redundant. (PMID:17255961)
• CstA, a secreted Brucella protein specifically interacts with human Sec24A. (PMID:22820839)
• the association between Kv1.3 and the COPII cargo adaptor subunit isoform Sec24a (PMID:26156069)
• The role of the C-terminal domain of PCSK9 and SEC24 isoforms in PCSK9 secretion. (PMID:32058034)
• CircRNA circ_SEC24A upregulates DNMT3A expression by sponging miR-26b-5p to aggravate osteoarthritis progression. (PMID:34325283)
• Selective inhibition of protein secretion by abrogating receptor-coat interactions during ER export. (PMID:35901214)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sec24a	ENSDARG00000104375
mus_musculus	Sec24a	ENSMUSG00000036391
rattus_norvegicus	Sec24a	ENSRNOG00000004563
drosophila_melanogaster	Sec24AB	FBGN0033460
caenorhabditis_elegans		WBGENE00004756

Paralogs (2): SEC24B (ENSG00000138802), SEC24D (ENSG00000150961)

Protein

Protein identifiers

Protein transport protein Sec24A — O95486 (reviewed: O95486)

Alternative names: SEC24-related protein A

All UniProt accessions (2): O95486, H0Y9J6

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 for their transport to the Golgi complex. Plays a central role in cargo selection within the COPII complex and together with SEC24B may have a different specificity compared to SEC24C and SEC24D. May package preferentially cargos with cytoplasmic DxE or LxxLE motifs and may also recognize conformational epitopes.

Subunit / interactions. COPII is composed of at least five proteins: the Sec23/24 complex, the Sec13/31 complex and Sar1. Interacts with TMED2. Interacts (as part of the Sec23/24 complex) with SEC22B; recruits SEC22B into COPII-coated vesicles for its transport from the endoplasmic reticulum to the Golgi. Interacts with STING1; promoting STING1 translocation to COPII vesicles in a STEEP1-dependent manner. Interacts with TMEM39A. Interacts with SACM1L; this interaction is reduced in the absence of TMEM39A. Interacts with kinase FAM20C; transport of FAM20C from the endoplasmic reticulum to the Golgi is likely to be mediated by COPII vesicles.

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

Similarity. Belongs to the SEC23/SEC24 family. SEC24 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O95486-1	1	yes
O95486-2	2

RefSeq proteins (2): NP_001239160, NP_068817* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006895	Znf_Sec23_Sec24	Domain
IPR006896	Sec23/24_trunk_dom	Domain
IPR006900	Sec23/24_helical_dom	Domain
IPR007123	Gelsolin-like_dom	Domain
IPR012990	Beta-sandwich_Sec23_24	Domain
IPR029006	ADF-H/Gelsolin-like_dom_sf	Homologous_superfamily
IPR036175	Sec23/24_helical_dom_sf	Homologous_superfamily
IPR036180	Gelsolin-like_dom_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR041742	Sec24-like_trunk_dom	Domain
IPR050550	SEC23_SEC24_subfamily	Family

Pfam: PF00626, PF04810, PF04811, PF04815, PF08033

UniProt features (95 total): strand 33, helix 29, turn 11, compositionally biased region 5, region of interest 5, binding site 4, sequence variant 3, splice variant 2, chain 1, repeat 1, mutagenesis site 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
2NUT	X-RAY DIFFRACTION	2.3
5VNL	X-RAY DIFFRACTION	2.39
5VNF	X-RAY DIFFRACTION	2.41
5VNN	X-RAY DIFFRACTION	2.5
9UVG	X-RAY DIFFRACTION	2.54
5VNK	X-RAY DIFFRACTION	2.55
5VNG	X-RAY DIFFRACTION	2.6
5VNH	X-RAY DIFFRACTION	2.6
9UVE	X-RAY DIFFRACTION	2.6
5VNE	X-RAY DIFFRACTION	2.7
3EGD	X-RAY DIFFRACTION	2.7
5VNM	X-RAY DIFFRACTION	2.77
5VNI	X-RAY DIFFRACTION	2.79
2NUP	X-RAY DIFFRACTION	2.8
5VNJ	X-RAY DIFFRACTION	2.81
5VNO	X-RAY DIFFRACTION	2.9
9UVD	X-RAY DIFFRACTION	2.98
9UVF	X-RAY DIFFRACTION	3.15
3EGX	X-RAY DIFFRACTION	3.3
8HR0	X-RAY DIFFRACTION	3.34

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95486-F1	76.63	0.61

Functional residue map

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

Ligand- & substrate-binding residues (4): 431; 434; 452; 455

Mutagenesis-validated functional residues (1):

Position	Phenotype
541	decreased ability to interact with and package the snare sec22b cargo into copii vesicles. has no effect on other cargos

Function

Pathways and Gene Ontology

Reactome pathways

25 pathways

ID	Pathway
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-2132295	MHC class II antigen presentation
R-HSA-5694530	Cargo concentration in the ER
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-983170	Antigen Presentation: Folding, assembly and peptide loading of class I MHC
R-HSA-1280218	Adaptive Immune System
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-556833	Metabolism of lipids
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-8957322	Metabolism of steroids
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9824446	Viral Infection Pathways
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 309 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, GOBP_STEROL_HOMEOSTASIS, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, BROWNE_HCMV_INFECTION_8HR_UP, GOBP_VESICLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOBP_LIPID_HOMEOSTASIS

GO Biological Process (8): intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), regulation of cholesterol transport (GO:0032374), cholesterol homeostasis (GO:0042632), positive regulation of protein secretion (GO:0050714), COPII-coated vesicle cargo loading (GO:0090110), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (4): SNARE binding (GO:0000149), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (9): endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), ER to Golgi transport vesicle membrane (GO:0012507), COPII vesicle coat (GO:0030127), endoplasmic reticulum exit site (GO:0070971), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	2
Metabolism of steroids	1
Adaptive Immune System	1
SARS-CoV-2-host interactions	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
Post-translational protein modification	1
Metabolism	1
Disease	1
Metabolism of proteins	1
Metabolism of lipids	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	4
intracellular transport	3
intracellular protein localization	2
transport	2
protein transport	1
intercellular transport	1
Golgi vesicle transport	1
cholesterol transport	1
regulation of sterol transport	1
sterol homeostasis	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
vesicle cargo loading	1
COPII-coated vesicle budding	1
establishment of protein localization	1
cellular process	1
protein binding	1
transition metal ion binding	1
binding	1
cation binding	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
coated vesicle membrane	1
ER to Golgi transport vesicle membrane	1
vesicle coat	1
endoplasmic reticulum	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular vesicle	1

Protein interactions and networks

STRING

1588 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEC24A	SEC13	P55735	962
SEC24A	SAR1B	Q9Y6B6	951
SEC24A	SAR1A	Q9NR31	895
SEC24A	SEC31A	O94979	888
SEC24A	PREB	Q9HCU5	883
SEC24A	SEC23B	Q15437	854
SEC24A	GOLPH3	Q9H4A6	847
SEC24A	MIA3	Q5JRA6	835
SEC24A	SEC23A	Q15436	791
SEC24A	CSTA	P01040	713
SEC24A	BET1	O15155	693
SEC24A	SEC16A	O15027	693
SEC24A	COPB1	P53618	660
SEC24A	SEC24D	O94855	647
SEC24A	SEC24C	P53992	637

IntAct

91 interactions, top by confidence:

A	B	Type	Score
SEC23B	SEC24D	psi-mi:“MI:0914”(association)	0.920
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
SEC23A	SEC24D	psi-mi:“MI:0914”(association)	0.690
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
SEC23B	SEC24A	psi-mi:“MI:0914”(association)	0.640
FGL1	LCMT2	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
EWSR1	SEC24A	psi-mi:“MI:0915”(physical association)	0.560
TFG	SEC24A	psi-mi:“MI:0915”(physical association)	0.560
SEC24A	TFG	psi-mi:“MI:0915”(physical association)	0.560
SEC23B	SEC16A	psi-mi:“MI:0914”(association)	0.530
TMED2	SEC24A	psi-mi:“MI:0915”(physical association)	0.400
SEC24A	CBFA2T3	psi-mi:“MI:0915”(physical association)	0.370
TRIP13	SEC24A	psi-mi:“MI:0915”(physical association)	0.370
GTSE1	HIP1	psi-mi:“MI:0914”(association)	0.350
SEC16A	NCOR2	psi-mi:“MI:0914”(association)	0.350
ERN1	SEC24D	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350

BioGRID (267): SEC24A (Two-hybrid), SEC24A (Two-hybrid), SEC24A (Affinity Capture-MS), SEC24A (Affinity Capture-MS), SEC24A (Two-hybrid), SEC24A (Co-fractionation), SEC24A (Co-fractionation), SEC24A (Co-fractionation), SEC24A (Co-fractionation), SEC24A (Affinity Capture-MS), SEC24A (Proximity Label-MS), SEC24A (Affinity Capture-MS), SEC24A (Affinity Capture-MS), SEC24A (Affinity Capture-MS), SEC24A (Affinity Capture-MS)

ESM2 similar proteins: A6QLK2, A6QNT8, D3ZMY7, D4A055, F1QH17, O00305, O35431, O95486, O95487, P40692, P49902, P54288, P56223, P97679, Q01973, Q0VGM9, Q13330, Q16514, Q1RMS5, Q3SWT1, Q3T174, Q3U2P1, Q3UNW5, Q3V1L4, Q5EBF1, Q5PYH5, Q5RA22, Q5RB16, Q5RE34, Q5RJZ1, Q5ZIZ4, Q61187, Q62599, Q6AY57, Q6DKB0, Q6H1L8, Q6IRE4, Q7ZWU5, Q80W47, Q80YA3

Diamond homologs: A1CUC3, A1DP06, A2QSG6, A3LRW3, A4QUL1, A5DPC0, A5DSK2, A6QNT8, O94855, O95486, O95487, P0CR40, P0CR41, P40482, P53953, P53992, Q0CSL7, Q0PVD8, Q1E6U9, Q2HH63, Q2ULI0, Q3U2P1, Q4P9K4, Q4WLP1, Q54U61, Q5AQ76, Q5B6W0, Q6BT80, Q6C2T4, Q6CLE0, Q6FWD3, Q6FX11, Q75B16, Q7S4P3, Q86ZK8, Q875Q0, Q875V7, Q875V8, Q876F4, Q876F5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SEC24A	“form complex”	“COPII vesicle”	binding
SAR1A	“up-regulates quantity”	SEC24A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 101 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	61.9×	4e-09
Activation of BAD and translocation to mitochondria	6	60.1×	6e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	53.0×	1e-07
Activation of BH3-only proteins	6	39.2×	5e-07
RHO GTPases activate PKNs	6	25.0×	6e-06
Intrinsic Pathway for Apoptosis	6	23.1×	8e-06
EPH-ephrin mediated repulsion of cells	6	17.3×	3e-05
Constitutive Signaling by Aberrant PI3K in Cancer	9	15.0×	5e-07

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	9	41.2×	4e-10
cell surface receptor protein tyrosine kinase signaling pathway	14	26.4×	2e-13
protein targeting	6	23.9×	3e-05
ephrin receptor signaling pathway	6	22.4×	3e-05
protein autophosphorylation	12	18.9×	5e-10
insulin receptor signaling pathway	5	12.1×	3e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	14	11.9×	3e-09
endoplasmic reticulum to Golgi vesicle-mediated transport	8	11.8×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	143
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3727 predictions. Top by Δscore:

Variant	Effect	Δscore
5:134649171:ACG:A	donor_gain	1.0000
5:134649171:ACGG:A	donor_loss	1.0000
5:134649173:GGT:G	donor_loss	1.0000
5:134649174:G:GG	donor_gain	1.0000
5:134649175:T:A	donor_loss	1.0000
5:134671803:TCTTA:T	acceptor_loss	1.0000
5:134671804:CTTAG:C	acceptor_loss	1.0000
5:134671805:TTAG:T	acceptor_loss	1.0000
5:134671806:TA:T	acceptor_loss	1.0000
5:134671808:G:GC	acceptor_loss	1.0000
5:134671872:G:GT	donor_gain	1.0000
5:134671882:ATTGG:A	donor_loss	1.0000
5:134671885:GG:G	donor_gain	1.0000
5:134671885:GGGTG:G	donor_loss	1.0000
5:134671886:GG:G	donor_gain	1.0000
5:134671887:G:GG	donor_gain	1.0000
5:134671887:GT:G	donor_loss	1.0000
5:134671888:T:A	donor_loss	1.0000
5:134671900:A:T	donor_gain	1.0000
5:134675216:GA:G	donor_gain	1.0000
5:134675218:G:GG	donor_gain	1.0000
5:134679597:TCCA:T	acceptor_loss	1.0000
5:134679600:A:AG	acceptor_gain	1.0000
5:134679601:G:GA	acceptor_gain	1.0000
5:134679601:GC:G	acceptor_gain	1.0000
5:134679601:GCA:G	acceptor_gain	1.0000
5:134679601:GCAA:G	acceptor_gain	1.0000
5:134679601:GCAAT:G	acceptor_gain	1.0000
5:134679603:A:AG	acceptor_gain	1.0000
5:134679652:G:GT	donor_gain	1.0000

AlphaMissense

7070 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:134676052:C:A	P394H	1.000
5:134676093:G:A	G408R	1.000
5:134676093:G:C	G408R	1.000
5:134676093:G:T	G408W	1.000
5:134676094:G:A	G408E	1.000
5:134676097:T:C	L409P	1.000
5:134679630:T:A	I428N	1.000
5:134679636:G:C	R430T	1.000
5:134679636:G:T	R430I	1.000
5:134679637:A:C	R430S	1.000
5:134679637:A:T	R430S	1.000
5:134679638:T:A	C431S	1.000
5:134679638:T:C	C431R	1.000
5:134679639:G:A	C431Y	1.000
5:134679639:G:C	C431S	1.000
5:134679639:G:T	C431F	1.000
5:134679640:C:G	C431W	1.000
5:134679647:T:A	C434S	1.000
5:134679647:T:C	C434R	1.000
5:134679648:G:A	C434Y	1.000
5:134679648:G:C	C434S	1.000
5:134679648:G:T	C434F	1.000
5:134679649:C:G	C434W	1.000
5:134679651:G:C	R435T	1.000
5:134679651:G:T	R435M	1.000
5:134679652:G:C	R435S	1.000
5:134679652:G:T	R435S	1.000
5:134679656:T:C	Y437H	1.000
5:134679656:T:G	Y437D	1.000
5:134679660:T:A	I438N	1.000

dbSNP variants (sampled 300 via entrez): RS1000005511 (5:134685850 G>A,C), RS1000066839 (5:134655269 G>A,T), RS1000104272 (5:134696606 C>G), RS1000204922 (5:134664701 T>C), RS1000227641 (5:134704178 T>C), RS1000261898 (5:134649881 A>G), RS1000360498 (5:134699546 G>A), RS1000362960 (5:134716007 T>C), RS1000518390 (5:134678989 A>G), RS1000547064 (5:134690763 T>C), RS1000554066 (5:134727936 A>C), RS1000611455 (5:134692745 T>C,G), RS1000611963 (5:134683946 A>G), RS1000654173 (5:134711110 T>C), RS1000656277 (5:134724655 G>C)

Disease associations

OMIM: gene MIM:607183 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): progressive muscular atrophy (MONDO:0018687)

Orphanet (1): Progressive muscular atrophy (Orphanet:454706)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Air Pollutants	increases abundance, decreases expression, affects expression	3
Tobacco Smoke Pollution	increases methylation, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Aflatoxin B1	decreases expression, decreases methylation	3
2,2’,4,4’-tetrabromodiphenyl ether	increases expression, decreases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Smoke	decreases expression, increases abundance	2
Valproic Acid	affects expression, decreases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
deoxynivalenol	decreases expression	1
trichostatin A	decreases expression	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	affects methylation	1
butylbenzyl phthalate	increases expression	1
aflatoxin B2	increases methylation	1
pentabromodiphenyl ether	increases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
abrine	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
jinfukang	affects cotreatment, decreases expression	1
PCI 5002	increases expression, affects cotreatment	1
Acetaminophen	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TK43	HAP1 SEC24A (-) 1	Cancer cell line	Male
CVCL_TK44	HAP1 SEC24A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00324454	PHASE2	COMPLETED	Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease
NCT03067857	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Therapy for Motor Neuron Disease
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02574390	Not specified	COMPLETED	Answer ALS: Individualized Initiative for ALS Discovery
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT03464903	Not specified	COMPLETED	Study of ALS Reversals 2: Genetic Analyses
NCT03489278	Not specified	RECRUITING	Clinical Procedures to Support Research in ALS
NCT03706391	Not specified	COMPLETED	Study of ALS Reversals 4: LifeTime Exposures
NCT03912987	Not specified	ACTIVE_NOT_RECRUITING	TRIAL READY (Clinical Trial Readiness)
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT05204017	Not specified	RECRUITING	Comprehensive Analysis Platform To Understand, Remedy and Eliminate ALS
NCT05271435	Not specified	ACTIVE_NOT_RECRUITING	Digital Tools for Assessment of Motor Functions and Falls in ALS
NCT06315673	Not specified	RECRUITING	Digital Assessment of Speech and Fine Motor Control in ALS
NCT07478172	Not specified	RECRUITING	Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease