SEC24C

Summary

SEC24C (SEC24 homolog C, COPII component, HGNC:10705) is a protein-coding gene on chromosome 10q22.2, encoding Protein transport protein Sec24C (P53992). 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 is a member of the SEC24 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec24p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The product of this gene may play a role in shaping the vesicle, as well as in cargo selection and concentration. Alternatively spliced transcript variants encoding the same protein have been identified.

Source: NCBI Gene 9632 — RefSeq curated summary.

At a glance

• Gene–disease (curated): 22q11.2 deletion syndrome (Supportive, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 194 total — 1 likely-pathogenic
• Phenotypes (HPO): 131
• Druggable target: yes
• MANE Select transcript: NM_198597

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10705
Approved symbol	SEC24C
Name	SEC24 homolog C, COPII component
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0079
Ensembl gene	ENSG00000176986
Ensembl biotype	protein_coding
OMIM	607185
Entrez	9632

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 26 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000339365, ENST00000345254, ENST00000465076, ENST00000477008, ENST00000496827, ENST00000634508, ENST00000635550, ENST00000893961, ENST00000893962, ENST00000893963, ENST00000893964, ENST00000893965, ENST00000893966, ENST00000893967, ENST00000893968, ENST00000893969, ENST00000893970, ENST00000893971, ENST00000893972, ENST00000939917, ENST00000939918, ENST00000939919, ENST00000939920, ENST00000939921, ENST00000939922, ENST00000939923, ENST00000939924, ENST00000939925, ENST00000939926, ENST00000958138

RefSeq mRNA: 2 — MANE Select: NM_198597 NM_004922, NM_198597

CCDS: CCDS7332

Canonical transcript exons

ENST00000345254 — 23 exons

Exon	Start	End
ENSE00000834043	73763856	73763983
ENSE00000834044	73763490	73763601
ENSE00000834045	73760713	73760849
ENSE00001024469	73760018	73760386
ENSE00001184185	73766086	73766210
ENSE00001184188	73765800	73765915
ENSE00001184192	73765451	73765589
ENSE00001611420	73770955	73772161
ENSE00001615079	73769347	73769485
ENSE00001622496	73769615	73769733
ENSE00001625331	73766760	73766853
ENSE00001652801	73770280	73770471
ENSE00001685418	73767837	73768007
ENSE00001723717	73770709	73770798
ENSE00002435205	73767054	73767170
ENSE00003463139	73746805	73747004
ENSE00003475983	73751108	73751243
ENSE00003479798	73766350	73766541
ENSE00003542948	73769007	73769152
ENSE00003543458	73759622	73759794
ENSE00003561092	73769836	73770015
ENSE00003660209	73768810	73768906
ENSE00003848048	73744372	73744437

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 96.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.2993 / max 469.0740, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105536	50.9768	1823
105537	1.2791	641
105538	0.0433	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.88	gold quality
esophagus squamous epithelium	UBERON:0006920	96.14	gold quality
epithelium of esophagus	UBERON:0001976	95.48	gold quality
pharyngeal mucosa	UBERON:0000355	95.39	gold quality
esophagus mucosa	UBERON:0002469	95.38	gold quality
islet of Langerhans	UBERON:0000006	95.10	gold quality
granulocyte	CL:0000094	94.98	gold quality
stromal cell of endometrium	CL:0002255	94.89	gold quality
adenohypophysis	UBERON:0002196	94.47	gold quality
right adrenal gland	UBERON:0001233	94.39	gold quality
pituitary gland	UBERON:0000007	94.33	gold quality
left adrenal gland	UBERON:0001234	94.21	gold quality
esophagus	UBERON:0001043	94.15	gold quality
right adrenal gland cortex	UBERON:0035827	94.02	gold quality
left adrenal gland cortex	UBERON:0035825	93.92	gold quality
adrenal gland	UBERON:0002369	93.72	gold quality
smooth muscle tissue	UBERON:0001135	93.71	gold quality
right coronary artery	UBERON:0001625	93.64	gold quality
ectocervix	UBERON:0012249	93.62	gold quality
adrenal cortex	UBERON:0001235	93.60	gold quality
body of stomach	UBERON:0001161	93.52	gold quality
right lobe of thyroid gland	UBERON:0001119	93.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.38	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.33	gold quality
cortical plate	UBERON:0005343	93.33	gold quality
left uterine tube	UBERON:0001303	93.32	gold quality
body of pancreas	UBERON:0001150	93.27	gold quality
gastrocnemius	UBERON:0001388	93.22	gold quality
oral cavity	UBERON:0000167	93.21	gold quality
body of uterus	UBERON:0009853	93.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	434.14
E-ANND-3	yes	4.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB3L2

miRNA regulators (miRDB)

104 targeting SEC24C, 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-4262	100.00	73.26	3931
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
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-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-5680	99.91	69.83	3421

Literature-anchored findings (GeneRIF, showing 11)

• The interphase form of Sec24Cp was O-N-acetylglucosamine modified, a feature lost upon entering into mitosis. This mitotic deglycosylation was coupled to Sec24p phosphorylation, a process which may contribute to observed mitotic ER-to-Golgi traffic block. (PMID:15013749)
• We found that Sec24C, a component of the host COPII vesicular transport system, interacts specifically with VP40 via VP40 amino acids 303 to 307. (PMID:18329616)
• The serotonin transporter is an exclusive client of the coat protein complex II (COPII) component SEC24C (PMID:21454670)
• A triple arg motif mediates alpha(2B)-adrenergic receptor interaction with Sec24C/D and export (PMID:22404651)
• a lysine residing in the C terminus of the serotonin transporter specifies its preference for the coat protein complex II component SEC24C (PMID:23288844)
• Data indicate that a synthetic polypeptide containing the N terminus of bovine AE1 bound the Sec23A-Sec24C complex through a selective interaction with Sec24C. (PMID:23658022)
• AKT signaling played a role in ATX secretion regulation to facilitate ATX ER export by enhancing the nuclear factor of activated T cell-mediated p23 (Sec24C) expression (PMID:28298439)
• Here, the authors identified an interaction between claudin-1 and Sec24C, a cargo-sorting component of the coat protein complex II (COPII) vesicular transport system. (PMID:28679754)
• These data suggest that SEC24C is a major cargo adapter for COPII-dependent transport in postmitotic neurons in developing and adult brains and that its functions overlap at least partially with those of SEC24D in mammals. (PMID:29939162)
• The role of the C-terminal domain of PCSK9 and SEC24 isoforms in PCSK9 secretion. (PMID:32058034)
• Sec24C is an HIV-1 host dependency factor crucial for virus replication. (PMID:33649557)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sec24c	ENSMUSG00000039367
rattus_norvegicus	Sec24c	ENSRNOG00000009042

Protein

Protein identifiers

Protein transport protein Sec24C — P53992 (reviewed: P53992)

Alternative names: SEC24-related protein C

All UniProt accessions (4): A0A0U1RR49, A0A0U1RR58, P53992, G5EA31

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 SEC24D may have a different specificity compared to SEC24A and SEC24B. May more specifically package GPI-anchored proteins through the cargo receptor TMED10. May also be specific for IxM motif-containing cargos like the SNAREs GOSR2 and STX5.

Subunit / interactions. COPII is composed of at least five proteins: the Sec23/24 complex, the Sec13/31 complex and Sar1. Interacts with TMED2 and TMED10. Interacts with GOSR2 (via IxM motif) and STX5 (via IxM motif); recruits GOSR2 and STX5 into COPII-coated vesicles. Interacts with DDHD1. Interacts with STING1; promoting STING1 translocation to the COPII vesicles.

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

Tissue specificity. Ubiquitous.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P53992-1	1	yes
P53992-2	2

RefSeq proteins (2): NP_004913, NP_940999* (*=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
IPR036174	Znf_Sec23_Sec24_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 (96 total): helix 32, strand 31, compositionally biased region 10, turn 10, binding site 4, region of interest 2, sequence variant 2, chain 1, repeat 1, modified residue 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6PU1	X-RAY DIFFRACTION	2.28
3EH2	X-RAY DIFFRACTION	2.35
8CL3	ELECTRON MICROSCOPY	3.14

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53992-F1	80.29	0.69

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): 425; 428; 447; 450

Post-translational modifications (1): 214

Mutagenesis-validated functional residues (1):

Position	Phenotype
895–897	loss of packaging into copii-coated vesicles of the ixm motif-containing cargos gosr2 and stx5.

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: 537 (showing top): MODULE_97, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, 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, SP3_Q3, ATACCTC_MIR202, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, MODULE_182, MORF_HDAC2, GOBP_VESICLE_MEDIATED_TRANSPORT, RIZKI_TUMOR_INVASIVENESS_3D_DN

GO Biological Process (6): in utero embryonic development (GO:0001701), intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), 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
chordate embryonic development	1
protein transport	1
intercellular transport	1
Golgi vesicle transport	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

1740 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEC24C	SEC13	P55735	963
SEC24C	SEC16A	O15027	948
SEC24C	SAR1A	Q9NR31	920
SEC24C	SEC31A	O94979	914
SEC24C	GOLPH3	Q9H4A6	840
SEC24C	LMAN1	P49257	830
SEC24C	SEC16B	Q96JE7	828
SEC24C	STX5	Q13190	782
SEC24C	ADRA2B	P18089	745
SEC24C	PREB	Q9HCU5	679
SEC24C	SEC23B	Q15437	668
SEC24C	SAR1B	Q9Y6B6	667
SEC24C	SEC24A	O95486	637
SEC24C	GOSR2	O14653	636
SEC24C	COPB1	P53618	633

IntAct

112 interactions, top by confidence:

A	B	Type	Score
SEC23B	SEC24D	psi-mi:“MI:0914”(association)	0.920
SEC23A	SEC24C	psi-mi:“MI:0407”(direct interaction)	0.810
SEC24C	SEC23A	psi-mi:“MI:0915”(physical association)	0.810
SEC23A	SEC24C	psi-mi:“MI:0915”(physical association)	0.810
SEC24C	SEC23B	psi-mi:“MI:0915”(physical association)	0.800
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SCYL1	SEC31A	psi-mi:“MI:0914”(association)	0.710
MOS	SEC24C	psi-mi:“MI:0915”(physical association)	0.670
SEC24C	MOS	psi-mi:“MI:0915”(physical association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
WIPF1	SEC24C	psi-mi:“MI:0915”(physical association)	0.560
SEC24C	FPR1	psi-mi:“MI:0915”(physical association)	0.560
SEC24C	CAF40	psi-mi:“MI:0915”(physical association)	0.560
CAF40	SEC24C	psi-mi:“MI:0915”(physical association)	0.560
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SEC23B	SEC16A	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

BioGRID (277): SEC24C (Two-hybrid), SEC24C (Two-hybrid), SEC24C (Affinity Capture-RNA), SEC24C (Affinity Capture-RNA), SEC24C (Affinity Capture-MS), SEC23B (Two-hybrid), CD2AP (Co-fractionation), SEC23A (Co-fractionation), SEC23B (Co-fractionation), SEC24A (Co-fractionation), SEC24C (Co-fractionation), SH3KBP1 (Co-fractionation), SEC24C (Affinity Capture-MS), SEC24C (Affinity Capture-MS), SEC24C (Proximity Label-MS)

ESM2 similar proteins: A3GFA2, A3LRW3, A5DJW8, A5DPC0, A5DSK2, A5E7S3, B0CS49, O94855, P0CR40, P0CR41, P15303, P38810, P38817, P40482, P53953, P53992, P87163, Q0CVT0, Q0PVD8, Q0U2G5, Q1DU75, Q2H401, Q2MHH3, Q2MHH4, Q4P9K4, Q54U61, Q5A455, Q5AQ76, Q5AVC7, Q6BT80, Q6C2T4, Q6CLE0, Q6CPH3, Q6FSI6, Q6FSK3, Q6FWD3, Q6FX11, Q75B16, Q7SDP4, Q84WV4

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
SEC24C	“form complex”	“COPII vesicle”	binding
SAR1A	“up-regulates quantity”	SEC24C	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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
Signaling by ALK fusions and activated point mutants	8	16.2×	2e-05
COPII-mediated vesicle transport	7	15.4×	8e-05
COPI-dependent Golgi-to-ER retrograde traffic	6	9.0×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	5	18.9×	1e-03
mitophagy	5	17.9×	1e-03
endoplasmic reticulum to Golgi vesicle-mediated transport	9	13.7×	2e-05
Golgi organization	6	9.0×	6e-03
autophagy	7	8.7×	2e-03
intracellular protein transport	8	5.8×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	140
Likely benign	6
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3600349	NM_198597.3(SEC24C):c.333del (p.Ser112fs)	Likely pathogenic

SpliceAI

3614 predictions. Top by Δscore:

Variant	Effect	Δscore
10:73746802:CAGG:C	acceptor_loss	1.0000
10:73746803:A:AG	acceptor_gain	1.0000
10:73746803:AG:A	acceptor_gain	1.0000
10:73746803:AGGT:A	acceptor_gain	1.0000
10:73746804:G:GG	acceptor_gain	1.0000
10:73746804:GG:G	acceptor_gain	1.0000
10:73746804:GGT:G	acceptor_gain	1.0000
10:73746804:GGTG:G	acceptor_gain	1.0000
10:73746804:GGTGA:G	acceptor_gain	1.0000
10:73747002:AAGGT:A	donor_loss	1.0000
10:73747003:AGGT:A	donor_loss	1.0000
10:73747004:GGTA:G	donor_loss	1.0000
10:73747005:G:GA	donor_loss	1.0000
10:73751102:CCTCA:C	acceptor_loss	1.0000
10:73751103:CTCAG:C	acceptor_loss	1.0000
10:73751104:TCAG:T	acceptor_loss	1.0000
10:73751105:CAGGT:C	acceptor_loss	1.0000
10:73751106:A:G	acceptor_loss	1.0000
10:73751107:G:GA	acceptor_loss	1.0000
10:73751241:AAGG:A	donor_loss	1.0000
10:73751242:AGGTA:A	donor_loss	1.0000
10:73751244:G:C	donor_loss	1.0000
10:73760845:GCCCT:G	donor_gain	1.0000
10:73760846:CCCT:C	donor_gain	1.0000
10:73760850:G:GG	donor_gain	1.0000
10:73765798:A:AG	acceptor_gain	1.0000
10:73765799:G:GA	acceptor_gain	1.0000
10:73766399:A:AG	acceptor_gain	1.0000
10:73766538:CCAG:C	donor_gain	1.0000
10:73766539:CAGG:C	donor_loss	1.0000

AlphaMissense

7083 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:73760842:C:A	P327Q	1.000
10:73765493:C:A	R424S	1.000
10:73765496:T:A	C425S	1.000
10:73765496:T:C	C425R	1.000
10:73765497:G:A	C425Y	1.000
10:73765497:G:C	C425S	1.000
10:73765497:G:T	C425F	1.000
10:73765498:C:G	C425W	1.000
10:73765505:T:A	C428S	1.000
10:73765505:T:C	C428R	1.000
10:73765506:G:A	C428Y	1.000
10:73765506:G:C	C428S	1.000
10:73765506:G:T	C428F	1.000
10:73765507:C:G	C428W	1.000
10:73765514:T:C	Y431H	1.000
10:73765535:T:C	F438L	1.000
10:73765537:C:A	F438L	1.000
10:73765537:C:G	F438L	1.000
10:73765547:G:T	G442W	1.000
10:73765548:G:A	G442E	1.000
10:73765548:G:T	G442V	1.000
10:73765562:T:C	C447R	1.000
10:73765564:C:G	C447W	1.000
10:73765571:T:C	C450R	1.000
10:73765572:G:A	C450Y	1.000
10:73765573:C:G	C450W	1.000
10:73765800:T:A	V456D	1.000
10:73765841:C:A	R470S	1.000
10:73765860:G:C	R476P	1.000
10:73765869:T:C	L479P	1.000

dbSNP variants (sampled 300 via entrez): RS1000008222 (10:73754347 A>C,G), RS1000017471 (10:73747698 T>C), RS1000107083 (10:73747760 A>C), RS1000419803 (10:73768682 A>G), RS1000443101 (10:73754006 A>G), RS1000871800 (10:73755041 G>A), RS1000928119 (10:73761997 A>G), RS1001155128 (10:73766924 A>G), RS1001508566 (10:73759068 T>C), RS1001712676 (10:73752897 C>G,T), RS1001813001 (10:73758176 G>A), RS1001837184 (10:73757876 G>A), RS1002012200 (10:73751621 T>C), RS1002037189 (10:73767535 GCA>G), RS1002086323 (10:73753124 A>G)

Disease associations

OMIM: gene MIM:607185 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
22q11.2 deletion syndrome	Supportive	Autosomal dominant

Mondo (3): developmental and epileptic encephalopathy (MONDO:0100620), microcephaly (MONDO:0001149), 22q11.2 deletion syndrome (MONDO:0018923)

Orphanet (0):

HPO phenotypes

131 total (30 of 131 shown, HPO-id order):

HPO	Term
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000076	Vesicoureteral reflux
HP:0000089	Renal hypoplasia
HP:0000113	Polycystic kidney dysplasia
HP:0000130	Abnormality of the uterus
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000262	Turricephaly
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000385	Small earlobe
HP:0000389	Chronic otitis media
HP:0000396	Overfolded helix
HP:0000405	Conductive hearing impairment
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000453	Choanal atresia

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004132_74	Crohn’s disease	2.000000e-09
GCST006620_9	Self-rated health	4.000000e-08
GCST007656_13	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	2.000000e-10
GCST012497_3	Lung function (FEV1)	5.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004778	self rated health
EFO:0004314	forced expiratory volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066868 (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
7.94	Kd	11.58	nM	CHEMBL3752910
7.94	ED50	11.58	nM	CHEMBL3752910
5.83	Kd	1461	nM	CHEMBL5653589
5.83	ED50	1461	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149366: Binding affinity to human SEC24C incubated for 45 mins by Kinobead based pull down assay	kd	0.0116	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149366: Binding affinity to human SEC24C incubated for 45 mins by Kinobead based pull down assay	kd	1.4610	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	4
sodium arsenite	decreases expression, increases abundance, affects binding, increases reaction	2
Air Pollutants	increases oxidation, decreases expression, affects cotreatment, increases abundance	2
Smoke	increases abundance, decreases expression	2
Aflatoxin B1	increases methylation	2
Volatile Organic Compounds	affects expression, affects cotreatment, increases oxidation	2
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	decreases expression, affects cotreatment, affects localization	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Mercury	increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Sodium Chloride	affects cotreatment, affects localization, decreases expression, increases expression	1
Dihydrotestosterone	increases expression	1
Tobacco Smoke Pollution	increases expression	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
CHEMBL5652408	Binding	Binding affinity to human SEC24C 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

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9RD	Ubigene HEK293 SEC24C KO	Transformed cell line	Female
CVCL_E0N9	Ubigene HeLa SEC24C KO	Cancer cell line	Female
CVCL_TK47	HAP1 SEC24C (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00395538	PHASE3	TERMINATED	Effects of PTH Replacement on Bone in Hypoparathyroidism
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT00576407	PHASE2	COMPLETED	Thymus Transplantation in DiGeorge Syndrome #668
NCT00576836	PHASE2	COMPLETED	Thymus Transplantation Dose in DiGeorge #932
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT05149898	PHASE2	COMPLETED	Open-Label Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome (INSPIRE)
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT00566488	PHASE1	COMPLETED	Parathyroid and Thymus Transplantation in DiGeorge #931
NCT00579709	PHASE1	COMPLETED	Thymus Transplantation With Immunosuppression
NCT02895906	PHASE1	COMPLETED	Safety and Efficacy Study of NFC-1 in Subjects Aged 12-17 Years With 22q11.2DS & Associated Neuropsychiatric Conditions
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00005102	Not specified	UNKNOWN	Immunologic Evaluation in Patients With DiGeorge Syndrome or Velocardiofacial Syndrome
NCT00105274	Not specified	COMPLETED	Velocardiofacial (VCFS; 22q11.2; DiGeorge) Syndrome Study
NCT00161109	Not specified	UNKNOWN	Genetics and Psychopathology in the 22q11 Deletion Syndrome
NCT00278005	Not specified	TERMINATED	Infection in DiGeorge Following CHD Surgery
NCT00556530	Not specified	RECRUITING	Examining Genetic Factors That Affect the Severity of 22q11.2 Deletion Syndrome
NCT00916955	Not specified	COMPLETED	Genetic Modifiers for 22q11.2 Syndrome
NCT01220531	Not specified	COMPLETED	Thymus Transplantation Safety-Efficacy
NCT01781923	Not specified	COMPLETED	Cognitive Remediation in 22q11DS
NCT02381457	Not specified	COMPLETED	SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
NCT02430584	Not specified	UNKNOWN	Whole Blood Specimen Collection From Pregnant Subjects
NCT02460328	Not specified	COMPLETED	Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome
NCT02787486	Not specified	COMPLETED	Expanded Noninvasive Genomic Medical Assessment: The Enigma Study
NCT03284060	Not specified	TERMINATED	Social Cognition Training and Cognitive Remediation
NCT03836300	Not specified	ENROLLING_BY_INVITATION	Parent and Infant Inter(X)Action Intervention (PIXI)
NCT04373226	Not specified	TERMINATED	Arithmetic Abilities in Children With 22q11.2DS
NCT04639388	Not specified	RECRUITING	Understanding of Psychotic Disorders in Children With 22q11.2DS
NCT04639960	Not specified	TERMINATED	Neuroprotective Effects of Risperdal on Brain and Cognition in 22q11 Deletion Syndrome
NCT04647500	Not specified	COMPLETED	Effects of Methylphenidate on Brain and Cognition in 22q11 Deletion Syndrome
NCT05924347	Not specified	RECRUITING	Early Scoliotic Changes in Children at Increased Risk for Scoliosis Development
NCT07493096	Not specified	RECRUITING	Intensive Multimodal Neurorehabilitation Targeting Neuroplasticity in Pediatric Neurodevelopmental and Chromosomal Disorders
NCT03876444	PHASE2/PHASE3	UNKNOWN	Intravenous Methylprednisolone Versus Oral Prednisolone for Infantile Spasms
NCT05279118	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome