SEC24D

Summary

SEC24D (SEC24 homolog D, COPII component, HGNC:10706) is a protein-coding gene on chromosome 4q26, encoding Protein transport protein Sec24D (O94855). 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. This gene product is implicated in the shaping of the vesicle, and also in cargo selection and concentration. Mutations in this gene have been associated with Cole-Carpenter syndrome, a disorder affecting bone formation, resulting in craniofacial malformations and bones that break easily. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 9871 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Cole-Carpenter syndrome 2 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 623 total — 26 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 47
• MANE Select transcript: NM_014822

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10706
Approved symbol	SEC24D
Name	SEC24 homolog D, COPII component
Location	4q26
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0755
Ensembl gene	ENSG00000150961
Ensembl biotype	protein_coding
OMIM	607186
Entrez	9871

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 10 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000280551, ENST00000419654, ENST00000502526, ENST00000502830, ENST00000503683, ENST00000505134, ENST00000505280, ENST00000506622, ENST00000509818, ENST00000511033, ENST00000511481, ENST00000511715, ENST00000514418, ENST00000514561, ENST00000899695, ENST00000899696, ENST00000924655, ENST00000924656, ENST00000924657, ENST00000924658

RefSeq mRNA: 2 — MANE Select: NM_014822 NM_001318066, NM_014822

CCDS: CCDS3710

Canonical transcript exons

ENST00000280551 — 23 exons

Exon	Start	End
ENSE00001762033	118722823	118723655
ENSE00001843854	118835941	118836126
ENSE00003481016	118740941	118741037
ENSE00003509768	118815028	118815155
ENSE00003510493	118797683	118797810
ENSE00003510684	118732733	118732912
ENSE00003518727	118731316	118731507
ENSE00003530187	118738261	118738379
ENSE00003534519	118743988	118744158
ENSE00003539639	118757721	118757845
ENSE00003564128	118744944	118745060
ENSE00003581891	118740663	118740808
ENSE00003599096	118739149	118739287
ENSE00003600837	118817264	118817412
ENSE00003610968	118764802	118764917
ENSE00003621660	118728561	118728650
ENSE00003640395	118805843	118805954
ENSE00003641233	118815451	118815726
ENSE00003646497	118768173	118768311
ENSE00003662752	118751996	118752089
ENSE00003669285	118824620	118824749
ENSE00003669813	118752697	118752888
ENSE00003680581	118833579	118833737

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 97.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.5629 / max 1026.3957, expressed in 1822 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53735	48.1491	1821
53734	2.6051	1252
53736	1.7350	1101
53737	1.0304	709
53738	0.0432	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.57	gold quality
jejunal mucosa	UBERON:0000399	97.28	gold quality
islet of Langerhans	UBERON:0000006	96.40	gold quality
ascending aorta	UBERON:0001496	94.61	gold quality
thoracic aorta	UBERON:0001515	94.55	gold quality
right coronary artery	UBERON:0001625	93.90	gold quality
pancreas	UBERON:0001264	93.89	gold quality
descending thoracic aorta	UBERON:0002345	93.74	gold quality
aorta	UBERON:0000947	93.73	gold quality
right lobe of liver	UBERON:0001114	93.60	gold quality
smooth muscle tissue	UBERON:0001135	93.57	gold quality
body of pancreas	UBERON:0001150	93.52	gold quality
tibia	UBERON:0000979	93.50	gold quality
popliteal artery	UBERON:0002250	93.22	gold quality
tibial artery	UBERON:0007610	93.22	gold quality
gall bladder	UBERON:0002110	93.20	gold quality
endocervix	UBERON:0000458	93.19	gold quality
left coronary artery	UBERON:0001626	93.02	gold quality
artery	UBERON:0001637	92.97	gold quality
calcaneal tendon	UBERON:0003701	92.95	gold quality
adenohypophysis	UBERON:0002196	92.52	gold quality
sperm	CL:0000019	92.48	gold quality
rectum	UBERON:0001052	92.45	gold quality
colonic epithelium	UBERON:0000397	92.29	gold quality
palpebral conjunctiva	UBERON:0001812	92.07	gold quality
coronary artery	UBERON:0001621	91.71	gold quality
left uterine tube	UBERON:0001303	91.55	gold quality
body of uterus	UBERON:0009853	91.46	gold quality
ectocervix	UBERON:0012249	91.37	gold quality
pituitary gland	UBERON:0000007	91.29	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.88
E-GEOD-99795	no	70.78
E-ENAD-27	no	3.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

100 targeting SEC24D, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-8062	99.88	68.43	995
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-8067	99.86	69.59	2260
HSA-LET-7G-3P	99.85	70.43	1929

Literature-anchored findings (GeneRIF, showing 8)

• concentrative endoplasmic reticulum-export is contingent on a direct interaction of GAT1 with Sec24D. (PMID:17210573)
• Mutations in the carboxyl-terminal SEC24 binding motif of the serotonin transporter impair folding of the transporter (PMID:20889976)
• A triple arg motif mediates alpha(2B)-adrenergic receptor interaction with Sec24C/D and export (PMID:22404651)
• three mutant SEC24D alleles in a rare autosomal-recessively inherited skeletal disorder characterized by pre- and postnatal bone fragility, skull ossification defects, craniofacial dysmorphism, and short stature (PMID:25683121)
• The study found missense mutations in the SEC24D gene in Chinese families with autosomal recessive osteogenesis imperfect. (PMID:27942778)
• Identification and characterization of SEC24D as a susceptibility gene for hepatitis B virus infection. (PMID:31530870)
• ERp29 as a regulator of Insulin biosynthesis. (PMID:32433667)
• Rare variant modifier analysis identifies variants in SEC24D associated with orofacial cleft subtypes. (PMID:37676273)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sec24d	ENSDARG00000045946
mus_musculus	Sec24d	ENSMUSG00000039234
rattus_norvegicus	Sec24d	ENSRNOG00000014872
drosophila_melanogaster	Sec24CD	FBGN0262126
caenorhabditis_elegans		WBGENE00004755

Paralogs (2): SEC24A (ENSG00000113615), SEC24B (ENSG00000138802)

Protein

Protein identifiers

Protein transport protein Sec24D — O94855 (reviewed: O94855)

Alternative names: SEC24-related protein D

All UniProt accessions (7): O94855, D6RAE2, D6RBM1, D6RGJ5, E9PC44, E9PDM8, E9PG84

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 SEC24C 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 CNIH4. Interacts with GOSR2 (via IxM motif) and STX5 (via IxM motif); recruits GOSR2 and STX5 into COPII-coated vesicles. Interacts with KCNA3; this interaction is reduced in the presence of KCNE4.

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

Tissue specificity. Ubiquitously expressed, with higher amounts in placenta, pancreas, heart and liver.

Disease relevance. Cole-Carpenter syndrome 2 (CLCRP2) [MIM:616294] A form of Cole-Carpenter syndrome, a disorder characterized by features of osteogenesis imperfecta such as bone deformities and severe bone fragility with frequent fractures, in association with craniosynostosis, ocular proptosis, hydrocephalus, growth failure and distinctive facial features. Craniofacial findings include marked frontal bossing, midface hypoplasia, and micrognathia. Despite the craniosynostosis and hydrocephalus, intellectual development is normal. CLCRP2 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O94855-1	1	yes
O94855-2	2

RefSeq proteins (2): NP_001304995, NP_055637* (*=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 (94 total): strand 36, helix 32, turn 8, sequence variant 5, binding site 4, region of interest 2, compositionally biased region 2, chain 1, repeat 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3EFO	X-RAY DIFFRACTION	2.7
3EG9	X-RAY DIFFRACTION	3
5KYW	X-RAY DIFFRACTION	3.2
5KYY	X-RAY DIFFRACTION	3.4
5KYU	X-RAY DIFFRACTION	3.51
5KYX	X-RAY DIFFRACTION	3.52

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94855-F1	83.21	0.71

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): 363; 366; 385; 388

Post-translational modifications (1): 266

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: 409 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, 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, GAANYNYGACNY_UNKNOWN, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOBP_VESICLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, MODULE_264, GOBP_VESICLE_MEDIATED_TRANSPORT

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

1050 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEC24D	SEC13	P55735	937
SEC24D	SEC31A	O94979	892
SEC24D	SAR1B	Q9Y6B6	881
SEC24D	SAR1A	Q9NR31	875
SEC24D	GOLPH3	Q9H4A6	799
SEC24D	PREB	Q9HCU5	780
SEC24D	TMEM38B	Q9NVV0	751
SEC24D	GOSR2	O14653	739
SEC24D	STX5	Q13190	737
SEC24D	SLC6A1	P30531	731
SEC24D	CREB3L1	Q96BA8	716
SEC24D	SEC23B	Q15437	711
SEC24D	SEC23A	Q15436	708
SEC24D	CRTAP	O75718	701
SEC24D	MBTPS2	O43462	683

IntAct

43 interactions, top by confidence:

A	B	Type	Score
SEC24D	SEC23B	psi-mi:“MI:0915”(physical association)	0.920
SEC23B	SEC24D	psi-mi:“MI:0915”(physical association)	0.920
SEC23B	SEC24D	psi-mi:“MI:0914”(association)	0.920
SEC23A	SEC24D	psi-mi:“MI:0914”(association)	0.690
SEC24D	SEC23A	psi-mi:“MI:0914”(association)	0.690
SEC24D	SEC23A	psi-mi:“MI:0407”(direct interaction)	0.690
EWSR1	SEC24D	psi-mi:“MI:0915”(physical association)	0.560
SEC24D	SF3B4	psi-mi:“MI:0915”(physical association)	0.560
SEC24D	EWSR1	psi-mi:“MI:0915”(physical association)	0.560
SF3B4	SEC24D	psi-mi:“MI:0915”(physical association)	0.560
PLEKHO1	UBA6	psi-mi:“MI:0914”(association)	0.530
SEC23B	SEC16A	psi-mi:“MI:0914”(association)	0.530
TMED10	SEC24D	psi-mi:“MI:0915”(physical association)	0.400
SEC24D	TMED2	psi-mi:“MI:0915”(physical association)	0.400
CDK18	SEC24D	psi-mi:“MI:0915”(physical association)	0.370
CDK16	SEC24D	psi-mi:“MI:0915”(physical association)	0.370
LMO4	SEC24D	psi-mi:“MI:0915”(physical association)	0.370
WWP2	SEC24D	psi-mi:“MI:0915”(physical association)	0.370
SEC24D	GCNT1	psi-mi:“MI:0915”(physical association)	0.370
ERN1	SEC24D	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
apa	NUDT21	psi-mi:“MI:0914”(association)	0.350
S	COPE	psi-mi:“MI:0914”(association)	0.350

BioGRID (83): SEC24D (Two-hybrid), SF3B4 (Two-hybrid), SEC23B (Two-hybrid), SEC24D (Affinity Capture-MS), SEC24D (Affinity Capture-MS), SEC23B (Two-hybrid), ARFIP1 (Co-fractionation), CD2AP (Co-fractionation), SEC23A (Co-fractionation), SEC23B (Co-fractionation), SEC24A (Co-fractionation), SEC24C (Co-fractionation), SH3KBP1 (Co-fractionation), SEC24D (Affinity Capture-MS), SEC24D (Two-hybrid)

ESM2 similar proteins: A3GFA2, A3LNJ3, A3LRW3, A5DA00, A5DJW8, A5DPC0, A5DSK2, A5E7S3, B0CS49, O74995, O94855, P0CR40, P0CR41, P15303, P38810, P38817, P40482, P53953, P87163, Q0PVD8, Q0U2G5, Q1DU75, Q2MHH3, Q2MHH4, Q4P9K4, Q54U61, Q5A455, Q5AQ76, Q5AVC7, Q6BQT6, Q6BT80, Q6BU98, Q6C2T4, Q6CLE0, Q6CPH3, Q6FSI6, Q6FSK3, Q6FWD3, Q6FX11, Q75B16

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
SEC24D	“form complex”	“COPII vesicle”	binding
SAR1A	“up-regulates quantity”	SEC24D	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	15
Uncertain significance	242
Likely benign	232
Benign	67

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1381110	NM_014822.4(SEC24D):c.2983C>T (p.Gln995Ter)	Pathogenic
1458019	NM_014822.4(SEC24D):c.1149T>A (p.Tyr383Ter)	Pathogenic
189339	NM_014822.4(SEC24D):c.3044C>T (p.Ser1015Phe)	Pathogenic
189340	NM_014822.4(SEC24D):c.613C>T (p.Gln205Ter)	Pathogenic
189341	NM_014822.4(SEC24D):c.2933A>C (p.Gln978Pro)	Pathogenic
1925313	NM_014822.4(SEC24D):c.150dup (p.Thr51fs)	Pathogenic
1974109	NM_014822.4(SEC24D):c.2055_2056insTATT (p.Gly686fs)	Pathogenic
2021257	NM_014822.4(SEC24D):c.2210_2211del (p.Leu737fs)	Pathogenic
2072182	NM_014822.4(SEC24D):c.267del (p.Val90fs)	Pathogenic
2081044	NM_014822.4(SEC24D):c.457C>T (p.Gln153Ter)	Pathogenic
2161361	NM_014822.4(SEC24D):c.19dup (p.Val7fs)	Pathogenic
2897888	NM_014822.4(SEC24D):c.469C>T (p.Arg157Ter)	Pathogenic
3606564	NM_014822.4(SEC24D):c.703C>T (p.Gln235Ter)	Pathogenic
3618466	NM_014822.4(SEC24D):c.1599del (p.Gln533fs)	Pathogenic
3661126	NM_014822.4(SEC24D):c.252del (p.Pro85fs)	Pathogenic
3727177	NM_014822.4(SEC24D):c.202C>T (p.Gln68Ter)	Pathogenic
4279086	NM_014822.4(SEC24D):c.2496+1811T>G	Pathogenic
4709154	NM_014822.4(SEC24D):c.1597C>T (p.Gln533Ter)	Pathogenic
4719845	NM_014822.4(SEC24D):c.2356dup (p.Ile786fs)	Pathogenic
4727455	NM_014822.4(SEC24D):c.2958+1G>T	Pathogenic
638178	NM_014822.4(SEC24D):c.113dup (p.Thr39fs)	Pathogenic
638179	NM_014822.4(SEC24D):c.2496G>T (p.Gln832His)	Pathogenic
638180	NM_014822.4(SEC24D):c.2723G>A (p.Cys908Tyr)	Pathogenic
638183	NM_014822.4(SEC24D):c.875C>T (p.Pro292Leu)	Pathogenic
638184	NM_014822.4(SEC24D):c.1450C>T (p.Arg484Ter)	Pathogenic
988313	NM_014822.4(SEC24D):c.788_789del (p.Ser263fs)	Pathogenic
1347994	NM_014822.4(SEC24D):c.673+2T>G	Likely pathogenic
1485902	NM_014822.4(SEC24D):c.248+2T>A	Likely pathogenic
2664317	NM_014822.4(SEC24D):c.1055T>A (p.Leu352Ter)	Likely pathogenic
2664324	NM_014822.4(SEC24D):c.1724G>C (p.Gly575Ala)	Likely pathogenic

SpliceAI

3710 predictions. Top by Δscore:

Variant	Effect	Δscore
4:118728652:T:C	acceptor_gain	1.0000
4:118728652:T:TC	acceptor_gain	1.0000
4:118728658:T:C	acceptor_gain	1.0000
4:118728658:T:TC	acceptor_gain	1.0000
4:118731506:TG:T	acceptor_gain	1.0000
4:118731507:GC:G	acceptor_loss	1.0000
4:118731508:C:CC	acceptor_gain	1.0000
4:118732731:A:AC	donor_gain	1.0000
4:118732732:C:CC	donor_gain	1.0000
4:118732909:TAAG:T	acceptor_gain	1.0000
4:118738255:GCTCA:G	donor_loss	1.0000
4:118738256:CTCA:C	donor_loss	1.0000
4:118738257:TCACC:T	donor_loss	1.0000
4:118738258:CACCT:C	donor_loss	1.0000
4:118738259:A:AC	donor_gain	1.0000
4:118738259:ACCT:A	donor_loss	1.0000
4:118738260:C:CC	donor_gain	1.0000
4:118738260:CCTGG:C	donor_gain	1.0000
4:118738375:AAAAG:A	acceptor_gain	1.0000
4:118738376:AAAG:A	acceptor_gain	1.0000
4:118738377:AAG:A	acceptor_gain	1.0000
4:118738378:AG:A	acceptor_gain	1.0000
4:118738380:C:A	acceptor_loss	1.0000
4:118738380:C:CC	acceptor_gain	1.0000
4:118738386:C:CT	acceptor_gain	1.0000
4:118738388:C:CT	acceptor_gain	1.0000
4:118738389:A:T	acceptor_gain	1.0000
4:118739148:CCTGA:C	donor_gain	1.0000
4:118739284:CACA:C	acceptor_gain	1.0000
4:118739286:CA:C	acceptor_gain	1.0000

AlphaMissense

6781 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:118740955:A:T	V693D	1.000
4:118764917:A:T	V394D	1.000
4:118768190:C:T	C388Y	1.000
4:118768200:A:G	C385R	1.000
4:118768257:A:G	C366R	1.000
4:118768264:G:C	C363W	1.000
4:118768265:C:G	C363S	1.000
4:118768265:C:T	C363Y	1.000
4:118768266:A:G	C363R	1.000
4:118768266:A:T	C363S	1.000
4:118738295:C:G	R821P	0.999
4:118739244:C:G	R761P	0.999
4:118739247:A:G	L760P	0.999
4:118739252:T:A	R758S	0.999
4:118739252:T:G	R758S	0.999
4:118739277:A:G	L750P	0.999
4:118739283:G:T	A748D	0.999
4:118740952:C:G	R694P	0.999
4:118740953:G:T	R694S	0.999
4:118740957:C:A	R692S	0.999
4:118740957:C:G	R692S	0.999
4:118740958:C:A	R692M	0.999
4:118752012:C:T	G564D	0.999
4:118752756:A:C	F518L	0.999
4:118752756:A:T	F518L	0.999
4:118752758:A:G	F518L	0.999
4:118752850:A:G	F487S	0.999
4:118764821:G:T	A426D	0.999
4:118764839:C:T	G420E	0.999
4:118764840:C:G	G420R	0.999

dbSNP variants (sampled 300 via entrez): RS10000269 (4:118771911 C>T), RS1000027683 (4:118789256 A>G), RS1000036257 (4:118737430 T>C), RS1000065334 (4:118733487 C>G), RS1000074748 (4:118783782 G>A,C), RS10000973 (4:118783895 T>C), RS10001659 (4:118808755 T>C), RS1000175005 (4:118730871 T>G), RS1000206369 (4:118770702 T>C,G), RS10002360 (4:118777811 C>T), RS1000279507 (4:118800969 G>A,C), RS1000286340 (4:118820187 T>C), RS1000311228 (4:118730465 T>A), RS1000322282 (4:118730765 G>T), RS1000337854 (4:118723822 T>C)

Disease associations

OMIM: gene MIM:607186 | disease phenotypes: MIM:616294

GenCC curated gene-disease

Disease	Classification	Inheritance
Cole-Carpenter syndrome 2	Strong	Autosomal recessive
Cole-Carpenter syndrome	Supportive	Autosomal dominant
osteogenesis imperfecta type 1	Supportive	Autosomal dominant
epilepsy	Limited	Autosomal recessive

Mondo (5): Cole-Carpenter syndrome 2 (MONDO:0014573), intellectual disability (MONDO:0001071), epilepsy (MONDO:0005027), Cole-Carpenter syndrome (MONDO:0016085), osteogenesis imperfecta type 1 (MONDO:0008146)

Orphanet (2): Cole-Carpenter syndrome (Orphanet:2050), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000262	Turricephaly
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000494	Downslanted palpebral fissures
HP:0000520	Proptosis
HP:0000592	Blue sclerae
HP:0000682	Abnormal dental enamel morphology
HP:0000684	Delayed eruption of teeth
HP:0000703	Dentinogenesis imperfecta
HP:0000767	Pectus excavatum
HP:0000772	Abnormal rib morphology
HP:0000883	Thin ribs
HP:0000926	Platyspondyly
HP:0000938	Osteopenia
HP:0000944	Abnormal metaphysis morphology
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001334	Communicating hydrocephalus
HP:0001382	Joint hypermobility
HP:0001511	Intrauterine growth retardation
HP:0001562	Oligohydramnios
HP:0001608	Abnormality of the voice
HP:0001620	Abnormally high-pitched voice
HP:0002007	Frontal bossing

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002892_11	Perioperative myocardial infarction in coronary artery bypass surgery	7.000000e-06
GCST002892_14	Perioperative myocardial infarction in coronary artery bypass surgery	9.000000e-06
GCST002892_15	Perioperative myocardial infarction in coronary artery bypass surgery	6.000000e-07
GCST003465_15	Cannabis dependence symptom count	2.000000e-07
GCST003465_16	Cannabis dependence symptom count	4.000000e-06
GCST90000025_281	Appendicular lean mass	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008457	cannabis dependence measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C535963	Cole Carpenter syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	7
sodium arsenite	decreases expression, increases expression, increases stability	5
Cyclosporine	increases expression	4
trichostatin A	affects cotreatment, increases expression	3
methylmercuric chloride	increases expression	2
bisphenol A	affects expression, decreases expression	2
entinostat	increases expression, affects cotreatment	2
2,2’,4,4’-tetrabromodiphenyl ether	increases expression, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Benzo(a)pyrene	decreases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression	2
Aflatoxin B1	affects cotreatment, decreases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
tremortin	increases expression	1
2,4,6-tribromophenol	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
lead acetate	increases expression	1
methylselenic acid	affects expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
ferrous chloride	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TK48	HAP1 SEC24D (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy