SEC13

Summary

SEC13 (SEC13 homolog, nuclear pore and COPII component, HGNC:10697) is a protein-coding gene on chromosome 3p25.3, encoding Protein SEC13 homolog (P55735). Functions as a component of the nuclear pore complex (NPC) and the COPII coat. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

The protein encoded by this gene belongs to the SEC13 family of WD-repeat proteins. It is a constituent of the endoplasmic reticulum and the nuclear pore complex. It has similarity to the yeast SEC13 protein, which is required for vesicle biogenesis from endoplasmic reticulum during the transport of proteins. Multiple alternatively spliced transcript variants have been found.

Source: NCBI Gene 6396 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 82 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_183352

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10697
Approved symbol	SEC13
Name	SEC13 homolog, nuclear pore and COPII component
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	SEC13R, npp-20
Ensembl gene	ENSG00000157020
Ensembl biotype	protein_coding
OMIM	600152
Entrez	6396

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 13 protein_coding, 9 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000337354, ENST00000350697, ENST00000383801, ENST00000397099, ENST00000397101, ENST00000397102, ENST00000397105, ENST00000397109, ENST00000397117, ENST00000428626, ENST00000431352, ENST00000432213, ENST00000445064, ENST00000476597, ENST00000477547, ENST00000479868, ENST00000482647, ENST00000490283, ENST00000492602, ENST00000873983, ENST00000873984, ENST00000931945, ENST00000931946

RefSeq mRNA: 5 — MANE Select: NM_183352 NM_001136026, NM_001136232, NM_001278946, NM_030673, NM_183352

CCDS: CCDS2599, CCDS46751, CCDS63540

Canonical transcript exons

ENST00000350697 — 9 exons

Exon	Start	End
ENSE00001029794	10300931	10301374
ENSE00001397686	10321050	10321112
ENSE00003486763	10305559	10305692
ENSE00003618484	10312579	10312730
ENSE00003646435	10318050	10318094
ENSE00003652241	10304026	10304172
ENSE00003679202	10311965	10312098
ENSE00003686780	10315321	10315436
ENSE00003692347	10305033	10305156

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.6313 / max 363.8277, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41039	74.2272	1822
41037	0.3098	167
41038	0.0943	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.57	gold quality
oocyte	CL:0000023	98.36	gold quality
pituitary gland	UBERON:0000007	98.35	gold quality
type B pancreatic cell	CL:0000169	98.28	gold quality
adenohypophysis	UBERON:0002196	98.14	gold quality
duodenum	UBERON:0002114	98.10	gold quality
jejunal mucosa	UBERON:0000399	98.03	gold quality
parotid gland	UBERON:0001831	97.94	gold quality
cartilage tissue	UBERON:0002418	97.74	gold quality
tibia	UBERON:0000979	97.67	gold quality
smooth muscle tissue	UBERON:0001135	97.44	gold quality
tendon of biceps brachii	UBERON:0008188	97.32	gold quality
secondary oocyte	CL:0000655	97.26	gold quality
palpebral conjunctiva	UBERON:0001812	97.20	gold quality
ileal mucosa	UBERON:0000331	97.15	gold quality
mucosa of transverse colon	UBERON:0004991	97.12	gold quality
saliva-secreting gland	UBERON:0001044	97.10	gold quality
ascending aorta	UBERON:0001496	97.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.05	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.05	gold quality
thoracic aorta	UBERON:0001515	97.04	gold quality
body of pancreas	UBERON:0001150	97.03	gold quality
small intestine	UBERON:0002108	97.02	gold quality
minor salivary gland	UBERON:0001830	96.92	gold quality
endocervix	UBERON:0000458	96.88	gold quality
placenta	UBERON:0001987	96.88	gold quality
periodontal ligament	UBERON:0008266	96.88	gold quality
mouth mucosa	UBERON:0003729	96.84	gold quality
colonic mucosa	UBERON:0000317	96.82	gold quality
amniotic fluid	UBERON:0000173	96.79	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	21.99
E-ANND-3	yes	20.11
E-GEOD-93593	no	528.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting SEC13, 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-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-4715-5P	97.62	67.47	506
HSA-MIR-6500-3P	97.42	67.20	867
HSA-MIR-376A-2-5P	96.43	68.06	715
HSA-MIR-1231	95.10	65.63	663

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• three-dimensional reconstruction of Sec13/31 cages at 30 A resolution using cryo-electron microscopy and single particle analysis (PMID:16407955)
• Determine crystal structure of Sec13-Nup145C dimer. (PMID:18160040)
• 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 identified Sec13 interaction to PS1 is a new candidate interaction for linking PS1 to secretory and protein degrading vesicular circuits. (PMID:19682973)
• When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. (PMID:22331354)
• GNL2 and SEC13 are required for nonsense-mediated mRNA decay pathway in human cells. (PMID:25452588)
• TRAPPC12, but not TRAPPC8, bound to Sec13/Sec31A tetramer but each Sec protein alone could not interact with TRAPPC12. (PMID:28240221)
• we demonstrated Sec13 as a novel component that was involved in VISA-mediated antiviral signaling pathway. (PMID:29948782)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sec13	ENSDARG00000054807
mus_musculus	Sec13	ENSMUSG00000030298
rattus_norvegicus	Sec13	ENSRNOG00000010628
rattus_norvegicus		ENSRNOG00000087590
drosophila_melanogaster	Sec13	FBGN0024509
caenorhabditis_elegans		WBGENE00003806

Paralogs (1): SEH1L (ENSG00000085415)

Protein

Protein identifiers

Protein SEC13 homolog — P55735 (reviewed: P55735)

Alternative names: GATOR2 complex protein SEC13, SEC13-like protein 1, SEC13-related protein

All UniProt accessions (6): P55735, A8MXL6, C9J0S2, C9JBJ5, C9JIB6, E7ERC8

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a component of the nuclear pore complex (NPC) and the COPII coat. At the endoplasmic reticulum, SEC13 is involved in the biogenesis of COPII-coated vesicles. Required for the exit of adipsin (CFD/ADN), an adipocyte-secreted protein from the endoplasmic reticulum. As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway. The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex. GATOR2 probably acts as an E3 ubiquitin-protein ligase toward GATOR1. In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation. In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex. Within the GATOR2 complex, SEC13 and SEH1L are required to stabilize the complex.

Subunit / interactions. At the nuclear pore: component of the Y-shaped Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex includes NUP160, NUP133, NUP107, NUP98, NUP85, NUP43, NUP37, SEH1 and SEC13. At the COPII coat complex: interacts with SEC31A and SEC31B. Interacts with SEC16A. Interacts with SEC16B. Component of the GATOR2 subcomplex, composed of MIOS, SEC13, SEH1L, WDR24 and WDR59. The GATOR2 complex interacts with CASTOR1 and CASTOR2; the interaction is negatively regulated by arginine. The GATOR2 complex interacts with SESN1, SESN2 and SESN3; the interaction is negatively regulated by amino acids.

Subcellular location. Cytoplasmic vesicle. COPII-coated vesicle membrane. Endoplasmic reticulum membrane. Nucleus. Nuclear pore complex. Lysosome membrane.

Activity regulation. The GATOR2 complex is negatively regulated by the upstream amino acid sensors CASTOR1 and SESN2, which sequester the GATOR2 complex in absence of amino acids. In the presence of abundant amino acids, GATOR2 is released from CASTOR1 and SESN2 and activated.

Similarity. Belongs to the WD repeat SEC13 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P55735-1	1	yes
P55735-2	2
P55735-3	3
P55735-4	4

RefSeq proteins (4): NP_001129498, NP_001129704, NP_109598, NP_899195* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR037363	Sec13/Seh1_fam	Family

Pfam: PF00400

UniProt features (48 total): strand 28, repeat 6, modified residue 3, splice variant 3, helix 2, turn 2, initiator methionine 1, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
3BG1	X-RAY DIFFRACTION	3
3BG0	X-RAY DIFFRACTION	3.15
9LWF	ELECTRON MICROSCOPY	3.41
9OTI	ELECTRON MICROSCOPY	3.5
9LVK	ELECTRON MICROSCOPY	3.59
7UHY	ELECTRON MICROSCOPY	3.66
9LVJ	ELECTRON MICROSCOPY	3.82
7R5K	ELECTRON MICROSCOPY	12
5A9Q	ELECTRON MICROSCOPY	23
7PEQ	ELECTRON MICROSCOPY	35
7R5J	ELECTRON MICROSCOPY	50

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55735-F1	90.44	0.79

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 (3): 309, 2, 184

Function

Pathways and Gene Ontology

Reactome pathways

106 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-159227	Transport of the SLBP independent Mature mRNA
R-HSA-159230	Transport of the SLBP Dependant Mature mRNA
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-165054	Rev-mediated nuclear export of HIV RNA
R-HSA-168271	Transport of Ribonucleoproteins into the Host Nucleus
R-HSA-168276	NS1 Mediated Effects on Host Pathways
R-HSA-168325	Viral Messenger RNA Synthesis
R-HSA-168333	NEP/NS2 Interacts with the Cellular Export Machinery
R-HSA-170822	Regulation of Glucokinase by Glucokinase Regulatory Protein
R-HSA-180746	Nuclear import of Rev protein
R-HSA-180910	Vpr-mediated nuclear import of PICs
R-HSA-1855170	IPs transport between nucleus and cytosol
R-HSA-1855196	IP3 and IP4 transport between cytosol and nucleus
R-HSA-1855229	IP6 and IP7 transport between cytosol and nucleus
R-HSA-191859	snRNP Assembly
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-2132295	MHC class II antigen presentation
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-3232142	SUMOylation of ubiquitinylation proteins
R-HSA-3301854	Nuclear Pore Complex (NPC) Disassembly
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-4085377	SUMOylation of SUMOylation proteins
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-4570464	SUMOylation of RNA binding proteins
R-HSA-4615885	SUMOylation of DNA replication proteins

MSigDB gene sets: 320 (showing top): REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, MORF_MBD4, MORF_RAB5A, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, MORF_RAD21

GO Biological Process (13): protein import into nucleus (GO:0006606), intracellular protein transport (GO:0006886), nucleocytoplasmic transport (GO:0006913), cellular response to nutrient levels (GO:0031669), positive regulation of TOR signaling (GO:0032008), protein exit from endoplasmic reticulum (GO:0032527), mRNA transport (GO:0051028), COPII-coated vesicle cargo loading (GO:0090110), COPII-coated vesicle budding (GO:0090114), negative regulation of TORC1 signaling (GO:1904262), positive regulation of TORC1 signaling (GO:1904263), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (3): structural molecule activity (GO:0005198), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (17): nuclear envelope (GO:0005635), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), lysosomal membrane (GO:0005765), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), ER to Golgi transport vesicle membrane (GO:0012507), COPII vesicle coat (GO:0030127), nuclear pore outer ring (GO:0031080), GATOR2 complex (GO:0061700), extracellular exosome (GO:0070062), kinetochore (GO:0000776), nucleus (GO:0005634), lysosome (GO:0005764), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	3
Inositol phosphate metabolism	3
Interactions of Rev with host cellular proteins	2
Influenza Infection	2
Antimicrobial mechanism of IFN-stimulated genes	1
Amplification of signal from the kinetochores	1
Transport of Mature Transcript to Cytoplasm	1
Late Phase of HIV Life Cycle	1
Influenza Viral RNA Transcription and Replication	1
Export of Viral Ribonucleoproteins from Nucleus	1
Glycolysis	1
Interactions of Vpr with host cellular proteins	1
Metabolism of non-coding RNA	1
ER to Golgi Anterograde Transport	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	3
intracellular protein transport	2
intracellular protein localization	2
intracellular transport	2
TORC1 signaling	2
regulation of TORC1 signaling	2
transport	2
endomembrane system	2
nuclear protein-containing complex	2
intracellular membrane-bounded organelle	2
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
protein transport	1
nuclear transport	1
response to nutrient levels	1
cellular response to stimulus	1
TOR signaling	1
regulation of TOR signaling	1
positive regulation of intracellular signal transduction	1
RNA transport	1
vesicle cargo loading	1
COPII-coated vesicle budding	1
endoplasmic reticulum to Golgi vesicle-mediated transport	1
vesicle budding from membrane	1
negative regulation of TOR signaling	1
positive regulation of TOR signaling	1
establishment of protein localization	1
cellular process	1
molecular_function	1
protein binding	1
binding	1
nucleus	1
organelle envelope	1
nuclear envelope	1
nuclear lumen	1
lysosome	1
lytic vacuole membrane	1
organelle membrane	1

Protein interactions and networks

STRING

3538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEC13	SEC24B	O95487	999
SEC13	NUP107	P57740	998
SEC13	NUP133	Q8WUM0	998
SEC13	NUP98	P52948	998
SEC13	NUP37	Q8NFH4	998
SEC13	NUP85	Q9BW27	997
SEC13	WDR24	Q96S15	997
SEC13	WDR59	Q6PJI9	996
SEC13	MIOS	Q9NXC5	996
SEC13	NUP43	Q8NFH3	996
SEC13	NUP160	Q12769	996
SEC13	SEC16A	O15027	994
SEC13	SEH1L	Q96EE3	991
SEC13	SEC31A	O94979	990
SEC13	SAR1B	Q9Y6B6	976

IntAct

181 interactions, top by confidence:

A	B	Type	Score
NUP120	NUP85	psi-mi:“MI:0915”(physical association)	0.960
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
CDK8	MED19	psi-mi:“MI:0914”(association)	0.850
SEC13	NUP37	psi-mi:“MI:0915”(physical association)	0.800
EGFR	GAPDH	psi-mi:“MI:0914”(association)	0.790
MIOS	SEC13	psi-mi:“MI:0914”(association)	0.790
SEC13	SEH1L	psi-mi:“MI:0915”(physical association)	0.770
SEH1L	SEC13	psi-mi:“MI:0915”(physical association)	0.770
PDCD6	SEC31A	psi-mi:“MI:0914”(association)	0.740
WDR24	SEC13	psi-mi:“MI:0914”(association)	0.730
WDR59	SEC13	psi-mi:“MI:0914”(association)	0.730
SEC31A	SEC13	psi-mi:“MI:0407”(direct interaction)	0.730
SEC31A	SEC13	psi-mi:“MI:0914”(association)	0.730
NUP133	NUP98	psi-mi:“MI:0914”(association)	0.730
SEC31A	SEC13	psi-mi:“MI:0915”(physical association)	0.730
SEC13	NUP145	psi-mi:“MI:0915”(physical association)	0.700
NUP145	SEC13	psi-mi:“MI:0915”(physical association)	0.700

BioGRID (352): SEC13 (Affinity Capture-MS), TRAF5 (Two-hybrid), SEC16B (Two-hybrid), SEC13 (Affinity Capture-MS), BCR (Affinity Capture-MS), NUP133 (Affinity Capture-MS), SPDL1 (Affinity Capture-MS), NUP98 (Affinity Capture-MS), SEH1L (Affinity Capture-MS), NUP160 (Affinity Capture-MS), SEC31A (Affinity Capture-MS), MIOS (Affinity Capture-MS), NUP85 (Affinity Capture-MS), PRPF38A (Affinity Capture-MS), NUP107 (Affinity Capture-MS)

ESM2 similar proteins: A1CGS0, A2QHM1, A3LNW3, A3LVM1, A4REK3, A5DHD9, A5DXE2, A8XJ40, B3NQR5, B4HRQ6, B4JW81, B4P7Q3, B4QFZ8, G0SA60, O64740, O80990, O94319, O96622, P0CS50, P0CS51, P53011, P53024, P55735, P78774, Q04491, Q0CHM0, Q0UNA9, Q1DZQ0, Q2GSM6, Q2UG43, Q3ZCC9, Q4PCB8, Q4WNK7, Q54DS8, Q5AEF2, Q5B563, Q5XFW8, Q6BIR1, Q6BZX5, Q6CBI8

Diamond homologs: A1CGS0, A2QHM1, A3LNW3, A4REK3, A5DHD9, A5DXE2, A6ZQL5, A7EZJ5, A7THX0, A7YY75, A8XJ40, B0XAF3, B6H7A3, C1BK83, C1GB49, C5FWH1, G0S8H7, G0SA60, O54929, O64740, O80990, O94319, P0CS50, P0CS51, P47025, P53024, P55735, Q04491, Q0CHM0, Q0UNA9, Q0V8J1, Q0VC24, Q1DZQ0, Q2GSM6, Q2UG43, Q32LP9, Q3ZCC9, Q4FZW5, Q4PCB8, Q4WNK7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SEC13	“form complex”	GATOR2	binding
SEC13	“form complex”	“COPII vesicle”	binding
SEC13	“form complex”	NPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 172 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
IPs transport between nucleus and cytosol	11	35.8×	8e-13
IP3 and IP4 transport between cytosol and nucleus	11	35.8×	8e-13
IP6 and IP7 transport between cytosol and nucleus	11	35.8×	8e-13
Postmitotic nuclear pore complex (NPC) reformation	10	34.9×	4e-12
Transport of Ribonucleoproteins into the Host Nucleus	11	33.5×	9e-13
Regulation of Glucokinase by Glucokinase Regulatory Protein	11	33.5×	9e-13
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	11	33.5×	9e-13
NEP/NS2 Interacts with the Cellular Export Machinery	11	32.5×	1e-12

GO biological processes:

GO term	Partners	Fold	FDR
clathrin coat assembly	6	37.2×	3e-06
RNA export from nucleus	5	32.7×	7e-05
nucleocytoplasmic transport	11	30.1×	6e-11
clathrin-dependent endocytosis	5	20.3×	7e-04
mRNA transport	11	20.2×	3e-09
negative regulation of TORC1 signaling	7	15.9×	7e-05
cellular response to amino acid starvation	6	13.3×	8e-04
positive regulation of TORC1 signaling	6	12.4×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1399 predictions. Top by Δscore:

Variant	Effect	Δscore
3:10304021:TGTA:T	donor_loss	1.0000
3:10304022:GTAC:G	donor_loss	1.0000
3:10304023:TAC:T	donor_loss	1.0000
3:10304024:A:AG	donor_loss	1.0000
3:10304168:CCATC:C	acceptor_gain	1.0000
3:10304169:CATC:C	acceptor_gain	1.0000
3:10304169:CATCC:C	acceptor_gain	1.0000
3:10304170:ATC:A	acceptor_gain	1.0000
3:10304171:TC:T	acceptor_gain	1.0000
3:10304172:CC:C	acceptor_gain	1.0000
3:10304172:CCTAG:C	acceptor_loss	1.0000
3:10304173:C:CC	acceptor_gain	1.0000
3:10304173:CTA:C	acceptor_loss	1.0000
3:10304174:T:G	acceptor_loss	1.0000
3:10305017:ATGG:A	donor_gain	1.0000
3:10305017:ATGGC:A	donor_gain	1.0000
3:10305155:CC:C	acceptor_gain	1.0000
3:10305156:CC:C	acceptor_gain	1.0000
3:10305554:CTT:C	donor_loss	1.0000
3:10305554:CTTA:C	donor_gain	1.0000
3:10305557:A:AC	donor_gain	1.0000
3:10305557:ACTT:A	donor_gain	1.0000
3:10305557:ACTTC:A	donor_gain	1.0000
3:10305558:C:CG	donor_gain	1.0000
3:10305558:CT:C	donor_gain	1.0000
3:10305558:CTT:C	donor_gain	1.0000
3:10305558:CTTC:C	donor_gain	1.0000
3:10305558:CTTCC:C	donor_gain	1.0000
3:10305560:T:TA	donor_gain	1.0000
3:10305689:CAAT:C	acceptor_gain	1.0000

AlphaMissense

2123 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:10301341:A:G	W297R	1.000
3:10301341:A:T	W297R	1.000
3:10301365:A:G	W289R	1.000
3:10301365:A:T	W289R	1.000
3:10304045:A:T	V279D	1.000
3:10304048:G:T	A278D	1.000
3:10304051:A:G	L277P	1.000
3:10304051:A:T	L277Q	1.000
3:10304071:C:A	W270C	1.000
3:10304071:C:G	W270C	1.000
3:10304073:A:G	W270R	1.000
3:10304073:A:T	W270R	1.000
3:10304085:A:G	W266R	1.000
3:10304085:A:T	W266R	1.000
3:10304172:C:G	D237H	1.000
3:10305039:G:C	C234W	1.000
3:10305040:C:T	C234Y	1.000
3:10305042:G:C	S233R	1.000
3:10305042:G:T	S233R	1.000
3:10305044:T:G	S233R	1.000
3:10305046:G:T	A232D	1.000
3:10305083:A:G	W220R	1.000
3:10305083:A:T	W220R	1.000
3:10305086:C:G	A219P	1.000
3:10305094:C:G	R216P	1.000
3:10305097:A:T	V215D	1.000
3:10305099:C:A	W214C	1.000
3:10305099:C:G	W214C	1.000
3:10305101:A:G	W214R	1.000
3:10305101:A:T	W214R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000526 (3:10304477 T>G), RS1000272185 (3:10303902 A>G), RS1000296017 (3:10302881 T>C), RS1000513850 (3:10308173 A>C,G,T), RS1000580618 (3:10309516 T>C), RS1000783685 (3:10314478 A>T), RS1000929221 (3:10320932 G>A,T), RS1000949633 (3:10308496 C>T), RS1000952673 (3:10308340 C>T), RS1000980138 (3:10320694 C>T), RS1001113423 (3:10314777 C>T), RS1001376268 (3:10320983 C>T), RS1001564669 (3:10314391 A>G), RS1001639412 (3:10303013 T>A), RS1001672002 (3:10303239 C>T)

Disease associations

OMIM: gene MIM:600152 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004521_106	Autism spectrum disorder or schizophrenia	2.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067369 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.31	Kd	4.933	nM	CHEMBL5653589
8.15	ED50	7.079	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149360: Binding affinity to human SEC13 incubated for 45 mins by Kinobead based pull down assay	kd	0.0049	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	affects expression, decreases expression, increases expression	3
Acetaminophen	decreases expression	2
Tunicamycin	increases expression	2
Cyclosporine	increases expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
beauvericin	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression	1
arsenite	decreases reaction, increases reaction, affects binding	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Aspirin	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases expression	1
Catechin	affects cotreatment, decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	affects expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652402	Binding	Binding affinity to human SEC13 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3GN	Abcam HEK293T SEC13 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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