SEC16A

Summary

SEC16A (SEC16 homolog A, endoplasmic reticulum export factor, HGNC:29006) is a protein-coding gene on chromosome 9q34.3, encoding Protein transport protein Sec16A (O15027). Acts as a molecular scaffold that plays a key role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). It is a selective cancer dependency (DepMap: 67.3% of cell lines).

This gene encodes a protein that forms part of the Sec16 complex. This protein has a role in protein transport from the endoplasmic reticulum (ER) to the Golgi and mediates COPII vesicle formation at the transitional ER. Alternative splicing results in multiple transcript variants that encode different protein isoforms.

Source: NCBI Gene 9919 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 467 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 67.3% of screened cell lines
• MANE Select transcript: NM_014866

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29006
Approved symbol	SEC16A
Name	SEC16 homolog A, endoplasmic reticulum export factor
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	p250, Sec16L
Ensembl gene	ENSG00000148396
Ensembl biotype	protein_coding
OMIM	612854
Entrez	9919

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 16 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000277537, ENST00000290037, ENST00000313050, ENST00000313084, ENST00000371706, ENST00000431893, ENST00000453963, ENST00000467838, ENST00000472305, ENST00000684901, ENST00000688052, ENST00000688461, ENST00000689049, ENST00000689439, ENST00000690691, ENST00000892822, ENST00000926658, ENST00000926659, ENST00000926660, ENST00000926661, ENST00000926662, ENST00000926663

RefSeq mRNA: 2 — MANE Select: NM_014866 NM_001276418, NM_014866

CCDS: CCDS55351, CCDS75936

Canonical transcript exons

ENST00000684901 — 32 exons

Exon	Start	End
ENSE00000984982	136447227	136447364
ENSE00000984984	136443823	136443900
ENSE00000984988	136446855	136446949
ENSE00000984989	136445645	136445719
ENSE00000984990	136445052	136445111
ENSE00001592620	136454109	136454327
ENSE00001594276	136463463	136463601
ENSE00001597267	136448084	136448161
ENSE00001605753	136459444	136459555
ENSE00001612640	136465962	136466136
ENSE00001621689	136453428	136453510
ENSE00001626602	136462887	136463132
ENSE00001646931	136461177	136461274
ENSE00001652294	136464420	136464562
ENSE00001654591	136455601	136455793
ENSE00001657080	136457444	136457584
ENSE00001658203	136471975	136472111
ENSE00001662996	136447853	136447909
ENSE00001665800	136456053	136456166
ENSE00001666012	136466957	136467083
ENSE00001702854	136447569	136447680
ENSE00001704446	136459757	136459874
ENSE00001732698	136468415	136468512
ENSE00001734079	136466264	136466462
ENSE00001742011	136460042	136460123
ENSE00001744569	136451256	136451408
ENSE00001767824	136463679	136463740
ENSE00001773304	136459134	136459239
ENSE00003721682	136474049	136477684
ENSE00003924496	136478709	136478830
ENSE00003926970	136440105	136441823
ENSE00003937896	136482938	136483040

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 96.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.4538 / max 401.0139, expressed in 1813 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103163	33.3322	1808
103164	4.0713	1496
103160	0.0503	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	96.85	gold quality
adenohypophysis	UBERON:0002196	96.43	gold quality
pituitary gland	UBERON:0000007	96.03	gold quality
right lobe of liver	UBERON:0001114	95.98	gold quality
cardia of stomach	UBERON:0001162	95.40	gold quality
pylorus	UBERON:0001166	95.30	gold quality
body of stomach	UBERON:0001161	95.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.68	gold quality
cervix squamous epithelium	UBERON:0006922	94.66	gold quality
body of pancreas	UBERON:0001150	94.49	gold quality
fundus of stomach	UBERON:0001160	94.42	gold quality
cerebellar hemisphere	UBERON:0002245	94.34	gold quality
cerebellar cortex	UBERON:0002129	94.26	gold quality
stomach	UBERON:0000945	93.98	gold quality
nasal cavity epithelium	UBERON:0005384	93.95	gold quality
mucosa of transverse colon	UBERON:0004991	93.91	gold quality
trachea	UBERON:0003126	93.88	gold quality
lower esophagus mucosa	UBERON:0035834	93.88	gold quality
cerebellum	UBERON:0002037	93.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.73	gold quality
prostate gland	UBERON:0002367	93.71	gold quality
stromal cell of endometrium	CL:0002255	93.65	gold quality
right frontal lobe	UBERON:0002810	93.65	gold quality
mucosa of stomach	UBERON:0001199	93.58	gold quality
spleen	UBERON:0002106	93.58	gold quality
upper lobe of lung	UBERON:0008948	93.51	gold quality
upper lobe of left lung	UBERON:0008952	93.50	gold quality
lower lobe of lung	UBERON:0008949	93.49	gold quality
granulocyte	CL:0000094	93.48	gold quality
skin of leg	UBERON:0001511	93.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting SEC16A, 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-4682	100.00	68.89	1258
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-378G	99.71	64.90	1106

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 67.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 14)

• Sar1-GTP-dependent assembly of Sec16 on the endoplasmic reticulum(ER) membrane forms an organized scaffold defining ER exit sites (PMID:17005010)
• Mammalian cells contain two distinct Sec16 homologues: a large protein Sec16L of 2154 aa and a smaller protein Sec16S of 1060 aa. (PMID:17192411)
• Results suggest that KIAA0310p, a mammalian homologue of yeast Sec16, builds up endoplasmic reticulum (ER) exit sites in cooperation with p125 and plays a role in membrane traffic from the ER. (PMID:17428803)
• These data are consistent with a model where Sec16 acts as a platform for COPII assembly at endoplasmic reticulum exit sites. (PMID:19638414)
• Sec16A remains associated with endoplasmic reticulum exit sites throughout mitosis. (PMID:21045114)
• Data show that knockdown of Sec16B but not Sec16A by RNAi affected the morphology of peroxisomes, inhibited the transport of Pex16 from the ER to peroxisomes, and suppressed expression of Pex3. (PMID:21768384)
• LRRK2 regulates the anterograde endoplasmic reticulum (ER)-Golgi transport through anchoring Sec16A at the endoplasmic reticulum exit sites (ERES). (PMID:25201882)
• growth factors modulate Sec16 protein levels and dynamics. Sec16 acts as part of a coherent feed-forward loop, which integrates secretion and growth factor signaling. (PMID:25526736)
• Results suggest that it is the presence of rare syntenic SEC16A and MAMDC4 deletions that increases susceptibility to axial spondyloarthritis in family members who carry the HLA-B*27 allele. (PMID:25956157)
• these findings highlight a novel function of Sec16A as an essential mediator of endoplasmic reticulum stress-associated unconventional secretion. (PMID:28067262)
• Mammalian endoplasmic reticulum exit sites are organized by TANGO1 acting as a scaffold, in cooperation with Sec16 for efficient secretion. (PMID:28442536)
• Nbeal2 interacts with Dock7, Sec16a, and Vac14. (PMID:29187380)
• Sec16A also stabilized the interacting ubiquitin ligase RNF152, which localizes to the lysosome and has structural similarity with RNF183 (PMID:29300766)
• SEC16A Variants Predispose to Chronic Pancreatitis by Impairing ER-to-Golgi Transport and Inducing ER Stress. (PMID:39119875)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sec16a	ENSMUSG00000026924
rattus_norvegicus	Sec16a	ENSRNOG00000019122
drosophila_melanogaster	Sec16	FBGN0052654
caenorhabditis_elegans		WBGENE00017419

Paralogs (1): SEC16B (ENSG00000120341)

Protein

Protein identifiers

Protein transport protein Sec16A — O15027 (reviewed: O15027)

Alternative names: SEC16 homolog A

All UniProt accessions (9): O15027, A0A0C4DH09, A0A3F2YNX0, A0A3F2YNZ0, A0A8I5KPG1, A0A8I5KQ88, F1T0I1, Q8N9G1, X6RGP5

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a molecular scaffold that plays a key role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). SAR1A-GTP-dependent assembly of SEC16A on the ER membrane forms an organized scaffold defining an ERES. Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus. Mediates the recruitment of MIA3/TANGO to ERES. Regulates both conventional (ER/Golgi-dependent) and GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane. Positively regulates the protein stability of E3 ubiquitin-protein ligases RNF152 and RNF183 and the ER localization of RNF183. Acts as a RAB10 effector in the regulation of insulin-induced SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the cell membrane in adipocytes.

Subunit / interactions. SEC16A and SEC16B are each present in multiple copies in a heteromeric complex. Interacts with SEC23A. Interacts with RNF183 and RNF152. Interacts with LRRK2 (via ROC domain). Interacts with SEC13. Interacts with RAB10. Interacts with MIA3. Interacts with GORASP2 in response to ER stress.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane. Cytoplasm. Perinuclear region. Cytosol. Microsome membrane.

Tissue specificity. Ubiquitous. Expressed at higher levels in the pancreas.

Similarity. Belongs to the SEC16 family.

Isoforms (5)

UniProt ID	Names	Canonical?
O15027-1	1	yes
O15027-2	2
O15027-3	3
O15027-4	4
O15027-5	5

RefSeq proteins (2): NP_001263347, NP_055681* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024298	Sec16_Sec23-bd	Domain
IPR024340	Sec16_CCD	Domain

Pfam: PF12931, PF12932

UniProt features (79 total): modified residue 35, region of interest 19, compositionally biased region 17, splice variant 4, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15027-F1	41.07	0.11

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 (35): 296, 314, 331, 559, 569, 587, 589, 592, 593, 595, 1069, 1207, 1229, 1305, 1325, 1327, 1347, 1350, 1356, 1359 …

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
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-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-948021	Transport to the Golgi and subsequent modification

MSigDB gene sets: 154 (showing top): MODULE_97, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_VESICLE_TARGETING, MODULE_182, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_PROTEIN_LOCALIZATION_TO_ENDOPLASMIC_RETICULUM, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_GOLGI_TO_PLASMA_MEMBRANE_TRANSPORT, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (15): obsolete regulation of COPII vesicle coating (GO:0003400), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi to plasma membrane transport (GO:0006893), endoplasmic reticulum organization (GO:0007029), Golgi organization (GO:0007030), substantia nigra development (GO:0021762), protein exit from endoplasmic reticulum (GO:0032527), response to endoplasmic reticulum stress (GO:0034976), protein stabilization (GO:0050821), protein localization to endoplasmic reticulum exit site (GO:0070973), protein localization to plasma membrane (GO:0072659), intracellular protein localization (GO:0008104), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), localization within membrane (GO:0051668)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (11): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), ER to Golgi transport vesicle membrane (GO:0012507), organelle membrane (GO:0031090), perinuclear region of cytoplasm (GO:0048471), endoplasmic reticulum exit site (GO:0070971), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Post-translational protein modification	1
Metabolism of proteins	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	6
cellular anatomical structure	5
organelle organization	2
endomembrane system organization	2
transport	2
endomembrane system	2
intracellular membrane-bounded organelle	2
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
post-Golgi vesicle-mediated transport	1
vesicle-mediated transport to the plasma membrane	1
midbrain development	1
neural nucleus development	1
intracellular protein transport	1
cellular response to stress	1
regulation of protein stability	1
protein localization to endoplasmic reticulum	1
protein localization to membrane	1
protein localization to cell periphery	1
macromolecule localization	1
intracellular protein localization	1
establishment of protein localization	1
cellular process	1
cellular localization	1
binding	1
Golgi apparatus	1
bounding membrane of 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
coated vesicle membrane	1
membrane	1
membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEC16A	SEC13	P55735	994
SEC16A	SEC24B	O95487	975
SEC16A	PREB	Q9HCU5	948
SEC16A	SEC24C	P53992	948
SEC16A	SEC31A	O94979	932
SEC16A	SAR1A	Q9NR31	908
SEC16A	SEC23A	Q15436	906
SEC16A	NTRK1	P04629	883
SEC16A	RGN	Q15493	881
SEC16A	LMAN1	P49257	879
SEC16A	MIA2	Q96PC5	842
SEC16A	GOLPH3	Q9H4A6	818
SEC16A	MIA3	Q5JRA6	795
SEC16A	SEC23B	Q15437	722
SEC16A	SEC24A	O95486	693

IntAct

304 interactions, top by confidence:

A	B	Type	Score
PSMA1	PSMA7	psi-mi:“MI:0914”(association)	0.950
PSMA1	PSMA7	psi-mi:“MI:2364”(proximity)	0.950
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
CDK8	MED19	psi-mi:“MI:0914”(association)	0.850
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
LRRK2	SEC16A	psi-mi:“MI:0915”(physical association)	0.650
SEC16A	LRRK2	psi-mi:“MI:0915”(physical association)	0.650
LRRK2	SEC16A	psi-mi:“MI:0403”(colocalization)	0.650
SEC16A	LRRK2	psi-mi:“MI:0403”(colocalization)	0.650
SEC16A	NBEAL2	psi-mi:“MI:0914”(association)	0.640
SEC16A	NBEAL2	psi-mi:“MI:0915”(physical association)	0.640
NBEAL2	SEC16A	psi-mi:“MI:0914”(association)	0.640
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
AURKB	SEC16A	psi-mi:“MI:0914”(association)	0.570
IRAK1	SEC16A	psi-mi:“MI:0914”(association)	0.530
CSNK1E	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
AIPL1	SUPT5H	psi-mi:“MI:0914”(association)	0.510
XPNPEP3	SEC16A	psi-mi:“MI:0914”(association)	0.510
DOCK7	SEC16A	psi-mi:“MI:0915”(physical association)	0.500
DOCK7	SEC16A	psi-mi:“MI:0914”(association)	0.500
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
SHC1	BCR/ABL fusion	psi-mi:“MI:0914”(association)	0.460
AIFM1	HAX1	psi-mi:“MI:0914”(association)	0.420
AIFM1	SEC16A	psi-mi:“MI:2364”(proximity)	0.420

BioGRID (576): SEC16A (Affinity Capture-MS), SEC16A (Affinity Capture-MS), SEC16A (Affinity Capture-MS), SEC16A (Affinity Capture-MS), SEC16A (Co-fractionation), SEC16A (Co-fractionation), SEC16A (Affinity Capture-MS), SEC16A (Affinity Capture-MS), SEC16A (Proximity Label-MS), SEC16A (Affinity Capture-MS), AP2A1 (Affinity Capture-MS), C4BPA (Affinity Capture-MS), CAD (Affinity Capture-MS), CLTA (Affinity Capture-MS), CLTB (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YXV3, A0A172M4N0, A2VE23, A5PL33, C7EMF5, E7EW31, F1NSM7, I3L273, O15027, O48582, O55189, O55196, O97939, P0C671, P0DV77, P14138, Q14D33, Q1XI13, Q28989, Q3B7M4, Q4R729, Q5R7U0, Q5SWP3, Q62840, Q63003, Q6E0U4, Q6H236, Q6NUN9, Q6UXA7, Q7Z2K8, Q86UU5, Q8BM15, Q8K4E0, Q8K4L6, Q8N1P7, Q8N3D4, Q96D09, Q96JG9, Q9BGL9, Q9D7G9

Diamond homologs: E9QAT4, O15027, Q6AW68, Q6BCB4, Q75N33, Q75NY9, Q91XT4, Q96JE7, Q9FGK9, Q9FGK8, Q6CEV2, Q9HEC9

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TFG	up-regulates	SEC16A	binding
SEC16A	“form complex”	“COPII vesicle”	binding
MAPK1	“up-regulates activity”	SEC16A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 191 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
RHO GTPases activate IQGAPs	5	13.7×	6e-04
HCMV Infection	5	12.9×	7e-04
Transcriptional Regulation by MECP2	5	12.6×	8e-04
Recycling pathway of L1	7	12.4×	8e-05
Centrosome maturation	6	12.1×	3e-04
The role of GTSE1 in G2/M progression after G2 checkpoint	9	11.5×	8e-06
Post NMDA receptor activation events	7	11.3×	1e-04
Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A	7	11.3×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
clathrin-dependent endocytosis	6	22.2×	1e-04
protein phosphorylation	19	8.2×	3e-09
Golgi organization	8	6.8×	6e-03
endocytosis	11	6.7×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	355
Likely benign	48
Benign	17

Top pathogenic / likely-pathogenic (0)

SpliceAI

4646 predictions. Top by Δscore:

Variant	Effect	Δscore
9:136447222:CCTA:C	donor_loss	1.0000
9:136447224:TACC:T	donor_loss	1.0000
9:136447225:ACCTG:A	donor_loss	1.0000
9:136447226:C:A	donor_loss	1.0000
9:136447360:TCCTG:T	acceptor_gain	1.0000
9:136447361:CCTGC:C	acceptor_gain	1.0000
9:136447362:CTG:C	acceptor_gain	1.0000
9:136447362:CTGC:C	acceptor_loss	1.0000
9:136447363:TG:T	acceptor_gain	1.0000
9:136447363:TGCT:T	acceptor_loss	1.0000
9:136447364:GC:G	acceptor_loss	1.0000
9:136447365:C:CC	acceptor_gain	1.0000
9:136447365:C:T	acceptor_loss	1.0000
9:136447366:T:A	acceptor_loss	1.0000
9:136447368:C:CT	acceptor_gain	1.0000
9:136447369:A:T	acceptor_gain	1.0000
9:136447676:TTCTT:T	acceptor_gain	1.0000
9:136447678:CTT:C	acceptor_gain	1.0000
9:136447679:TT:T	acceptor_gain	1.0000
9:136447681:C:A	acceptor_loss	1.0000
9:136447681:C:CC	acceptor_gain	1.0000
9:136447682:T:G	acceptor_loss	1.0000
9:136447854:T:TA	donor_gain	1.0000
9:136448078:ACTC:A	donor_loss	1.0000
9:136448079:CTCA:C	donor_loss	1.0000
9:136448080:TCA:T	donor_loss	1.0000
9:136448081:CACCG:C	donor_loss	1.0000
9:136448082:A:AC	donor_gain	1.0000
9:136448082:ACC:A	donor_loss	1.0000
9:136448083:C:CA	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008267 (9:136443038 C>T), RS1000030222 (9:136457157 AGAGT>A), RS1000051242 (9:136484519 C>G,T), RS1000056662 (9:136456876 A>G), RS1000059244 (9:136478042 G>A), RS1000083247 (9:136482637 G>A,T), RS1000092497 (9:136451824 T>C), RS1000203525 (9:136479943 A>C), RS1000313458 (9:136473309 G>A), RS1000414466 (9:136468359 G>A,C,T), RS1000457649 (9:136486284 C>T), RS1000474140 (9:136458256 G>A), RS1000474925 (9:136468692 C>A,T), RS1000486998 (9:136441491 C>G,T), RS1000584330 (9:136463368 G>A,T)

Disease associations

OMIM: gene MIM:612854 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST000964_39	Ulcerative colitis	3.000000e-19
GCST003655_7	Cutaneous squamous cell carcinoma	8.000000e-09
GCST004131_21	Inflammatory bowel disease	5.000000e-36
GCST004132_11	Crohn’s disease	6.000000e-30
GCST004133_17	Ulcerative colitis	2.000000e-16
GCST004606_4	Eosinophil count	3.000000e-09
GCST008163_563	Height	2.000000e-06
GCST008871_15	Basal cell carcinoma	4.000000e-06
GCST008872_12	Squamous cell carcinoma	2.000000e-10
GCST010148_15	Cutaneous squamous cell carcinoma	2.000000e-11
GCST010173_145	Triglyceride levels	2.000000e-09
GCST012490_38	Femur bone mineral density x serum urate levels interaction	7.000000e-12
GCST90002394_335	Monocyte percentage of white cells	2.000000e-27
GCST90011900_212	Serum alkaline phosphatase levels	4.000000e-19

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:1001927	cutaneous squamous cell carcinoma
EFO:0004842	eosinophil count
EFO:0004530	triglyceride measurement
EFO:0004531	urate measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295654 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.28	Kd	5.204	nM	CHEMBL5653589
8.28	ED50	5.204	nM	CHEMBL5653589
8.17	Kd	6.746	nM	CHEMBL3752910
8.17	ED50	6.746	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 6 total; 2 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	2149361: Binding affinity to human SEC16A incubated for 45 mins by Kinobead based pull down assay	kd	0.0052	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149361: Binding affinity to human SEC16A incubated for 45 mins by Kinobead based pull down assay	kd	0.0067	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol A	affects reaction, decreases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression, affects cotreatment	2
Valproic Acid	affects expression, increases methylation	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases methylation	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization, decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
tamibarotene	decreases expression	1
K 7174	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	decreases expression, increases abundance, increases expression, affects cotreatment	1
Vehicle Emissions	increases abundance, increases expression	1
Benzene	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118665	Binding	Binding affinity to SEC16A in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2EX	Abcam HeLa SEC16A KO	Cancer cell line	Female
CVCL_ZV46	UCD178	Cancer cell line	Female

Clinical trials (associated diseases)

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