SEC24B

Summary

SEC24B (SEC24 homolog B, COPII component, HGNC:10704) is a protein-coding gene on chromosome 4q25, encoding Protein transport protein Sec24B (O95487). 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 is thought to be a cargo-binding component of the COPII vesicle, and is thought to be involved in the transport of secretory proteins from the endoplasmic reticulum to the Golgi apparatus. Mutations in this gene have been associated with neural tube defects, and are thought to be a result of a disruption in interactions with the protein encoded by the VANGL planar cell polarity protein 2 (VANGL2) gene. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 10427 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 226 total
• MANE Select transcript: NM_006323

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10704
Approved symbol	SEC24B
Name	SEC24 homolog B, COPII component
Location	4q25
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138802
Ensembl biotype	protein_coding
OMIM	607184
Entrez	10427

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 28 protein_coding

ENST00000265175, ENST00000399100, ENST00000504968, ENST00000898580, ENST00000898581, ENST00000898582, ENST00000898583, ENST00000898584, ENST00000898585, ENST00000898586, ENST00000898587, ENST00000898588, ENST00000898589, ENST00000898590, ENST00000898591, ENST00000898592, ENST00000934093, ENST00000934094, ENST00000934095, ENST00000934096, ENST00000934097, ENST00000934098, ENST00000934099, ENST00000950643, ENST00000950644, ENST00000950645, ENST00000950646, ENST00000950647

RefSeq mRNA: 5 — MANE Select: NM_006323 NM_001042734, NM_001300813, NM_001318085, NM_001318086, NM_006323

CCDS: CCDS43260, CCDS47124, CCDS75179

Canonical transcript exons

ENST00000265175 — 24 exons

Exon	Start	End
ENSE00000935025	109506328	109506512
ENSE00000935026	109510009	109510111
ENSE00000935029	109516528	109516640
ENSE00000935030	109520366	109520484
ENSE00000935032	109521420	109521626
ENSE00000935033	109524818	109524941
ENSE00000935034	109525346	109525504
ENSE00000935035	109526226	109526399
ENSE00000935036	109527322	109527432
ENSE00000935038	109531385	109531522
ENSE00000935039	109532639	109532743
ENSE00000935040	109533593	109533685
ENSE00000935041	109538493	109538596
ENSE00001018831	109511957	109512083
ENSE00001018834	109481677	109481781
ENSE00001018844	109491327	109491407
ENSE00001176497	109530289	109530464
ENSE00001205766	109473004	109473186
ENSE00001298686	109462901	109463644
ENSE00001309369	109539561	109540896
ENSE00001536414	109494615	109494856
ENSE00002081193	109433815	109434002
ENSE00002493574	109521117	109521172
ENSE00002506396	109513747	109513856

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 96.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.5281 / max 391.5500, expressed in 1825 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49223	48.5281	1825

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	96.19	gold quality
skin of hip	UBERON:0001554	95.43	gold quality
upper leg skin	UBERON:0004262	95.17	gold quality
pigmented layer of retina	UBERON:0001782	94.71	gold quality
retina	UBERON:0000966	94.68	gold quality
biceps brachii	UBERON:0001507	94.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.60	gold quality
jejunal mucosa	UBERON:0000399	94.50	gold quality
germinal epithelium of ovary	UBERON:0001304	94.19	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.77	gold quality
choroid plexus epithelium	UBERON:0003911	93.61	gold quality
caput epididymis	UBERON:0004358	93.34	gold quality
colonic mucosa	UBERON:0000317	93.31	gold quality
tibialis anterior	UBERON:0001385	93.26	gold quality
amniotic fluid	UBERON:0000173	93.24	gold quality
oral cavity	UBERON:0000167	93.23	gold quality
deltoid	UBERON:0001476	93.22	gold quality
blood vessel layer	UBERON:0004797	93.22	gold quality
cauda epididymis	UBERON:0004360	93.21	gold quality
jejunum	UBERON:0002115	93.13	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.01	gold quality
bronchial epithelial cell	CL:0002328	92.92	gold quality
lower lobe of lung	UBERON:0008949	92.89	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.83	gold quality
corpus epididymis	UBERON:0004359	92.76	gold quality
superficial temporal artery	UBERON:0001614	92.53	gold quality
heart right ventricle	UBERON:0002080	92.48	gold quality
quadriceps femoris	UBERON:0001377	92.33	gold quality
vastus lateralis	UBERON:0001379	92.31	gold quality
eye	UBERON:0000970	92.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.30
E-GEOD-110499	no	710.96
E-GEOD-124858	no	387.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting SEC24B, 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-190A-3P	100.00	80.35	5520
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3660	99.68	67.33	1149

Literature-anchored findings (GeneRIF, showing 4)

• Data show that coupling of the Sec23/24 and Sec13/31 layers of the COPII coat is required to drive export of collagen from the endoplasmic reticulum, and that efficient COPII assembly is essential for normal craniofacial development during embryogenesis. (PMID:18713835)
• results show that functional mutations in SEC24B might contribute to the etiology of a subset of human Neural Tube Defects (NTDs). (PMID:23592378)
• The role of the C-terminal domain of PCSK9 and SEC24 isoforms in PCSK9 secretion. (PMID:32058034)
• Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration. (PMID:36536241)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sec24b	ENSDARG00000071906
mus_musculus	Sec24b	ENSMUSG00000001052
rattus_norvegicus	Sec24b	ENSRNOG00000023373
drosophila_melanogaster	Sec24AB	FBGN0033460
caenorhabditis_elegans		WBGENE00004756

Paralogs (2): SEC24A (ENSG00000113615), SEC24D (ENSG00000150961)

Protein

Protein identifiers

Protein transport protein Sec24B — O95487 (reviewed: O95487)

Alternative names: SEC24-related protein B

All UniProt accessions (1): O95487

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 SEC24A may have a different specificity compared to SEC24C and SEC24D. May package preferentially cargos with cytoplasmic DxE or LxxLE motifs and may also recognize conformational epitopes.

Subunit / interactions. COPII is composed of at least five proteins: the Sec23/24 complex, the Sec13/31 complex and SAR1. Interacts with STING1; promoting STING1 translocation to COPII vesicles in a STEEP1-dependent manner. Interacts with RNF139. Interacts with TMED2 and TMED10. Interacts with CNIH4.

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

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

Isoforms (3)

UniProt ID	Names	Canonical?
O95487-1	1	yes
O95487-2	2
O95487-3	3

RefSeq proteins (5): NP_001036199, NP_001287742, NP_001305014, NP_001305015, NP_006314* (*=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 (101 total): helix 31, strand 30, turn 10, compositionally biased region 8, region of interest 5, modified residue 4, binding site 4, splice variant 3, initiator methionine 1, chain 1, repeat 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3EH1	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95487-F1	72.63	0.55

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): 605; 608; 626; 629

Post-translational modifications (4): 55, 2, 329, 1224

Mutagenesis-validated functional residues (1):

Position	Phenotype
715	decreased ability to package the snare sec22b cargo into copii vesicles. has no effect on other cargos packaging.

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: 260 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, chr4q25, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, 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, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_LUNG_MORPHOGENESIS

GO Biological Process (18): neural tube closure (GO:0001843), outflow tract morphogenesis (GO:0003151), intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), cochlear nucleus development (GO:0021747), aorta morphogenesis (GO:0035909), auditory receptor cell stereocilium organization (GO:0060088), lung lobe morphogenesis (GO:0060463), coronary artery morphogenesis (GO:0060982), pulmonary artery morphogenesis (GO:0061156), COPII-coated vesicle cargo loading (GO:0090110), regulation of establishment of planar polarity involved in neural tube closure (GO:0090178), regulation of cargo loading into COPII-coated vesicle (GO:1901301), auditory receptor cell morphogenesis (GO:0002093), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), lung morphogenesis (GO:0060425), circulatory system development (GO:0072359)

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
artery morphogenesis	3
anatomical structure morphogenesis	2
intracellular protein localization	2
transport	2
primary neural tube formation	1
tube closure	1
heart morphogenesis	1
protein transport	1
intercellular transport	1
Golgi vesicle transport	1
pons development	1
neural nucleus development	1
aorta development	1
auditory receptor cell morphogenesis	1
inner ear receptor cell stereocilium organization	1
lung morphogenesis	1
lung lobe development	1
coronary vasculature morphogenesis	1
vesicle cargo loading	1
COPII-coated vesicle budding	1
regulation of establishment of planar polarity	1
establishment of planar polarity involved in neural tube closure	1
regulation of intracellular transport	1
COPII-coated vesicle cargo loading	1
inner ear morphogenesis	1
embryonic morphogenesis	1
cell morphogenesis involved in neuron differentiation	1
auditory receptor cell development	1
establishment of protein localization	1
cellular process	1
animal organ morphogenesis	1
lung development	1
system development	1
protein binding	1
transition metal ion binding	1
binding	1
cation binding	1

Protein interactions and networks

STRING

2322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEC24B	SEC13	P55735	999
SEC24B	SEC16A	O15027	975
SEC24B	MIA3	Q5JRA6	971
SEC24B	PREB	Q9HCU5	965
SEC24B	GOLPH3	Q9H4A6	946
SEC24B	SEC31A	O94979	933
SEC24B	YIPF5	Q969M3	928
SEC24B	SAR1A	Q9NR31	928
SEC24B	SAR1B	Q9Y6B6	923
SEC24B	BET1	O15155	854
SEC24B	SEC23A	Q15436	854
SEC24B	MIA2	Q96PC5	781
SEC24B	SURF4	O15260	778
SEC24B	SEC31B	Q9NQW1	743
SEC24B	SLC6A4	P31645	723

IntAct

127 interactions, top by confidence:

A	B	Type	Score
SEC23B	SEC24D	psi-mi:“MI:0914”(association)	0.920
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SEC23A	SEC24D	psi-mi:“MI:0914”(association)	0.690
SEC24B	SEC23A	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
SEC13	SEC16A	psi-mi:“MI:0914”(association)	0.640
SEC23B	SEC24A	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
SEC24B	espI	psi-mi:“MI:0915”(physical association)	0.550
RPN1	APBB1	psi-mi:“MI:0914”(association)	0.530
SEC23B	SEC16A	psi-mi:“MI:0914”(association)	0.530
	SEC24B	psi-mi:“MI:0915”(physical association)	0.490
PLCG1	SEC24B	psi-mi:“MI:0915”(physical association)	0.400
SEC24B	TMED10	psi-mi:“MI:0915”(physical association)	0.400
SEC24B	TMED2	psi-mi:“MI:0915”(physical association)	0.400
SEC24B	RAB11FIP1	psi-mi:“MI:0915”(physical association)	0.400
ERN1	SEC24D	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
nleA/espI	SEC24B	psi-mi:“MI:0914”(association)	0.350
espI	DLG1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350

BioGRID (319): SEC24B (Affinity Capture-MS), SEC24B (Affinity Capture-MS), SEC24B (Affinity Capture-MS), SEC24B (Co-fractionation), SEC24B (Co-fractionation), SEC24B (Co-fractionation), SEC24B (Co-fractionation), SEC24B (Co-fractionation), SEC24B (Co-fractionation), VBP1 (Co-fractionation), SEC24B (Proximity Label-MS), SEC24B (Proximity Label-MS), SEC24B (Proximity Label-MS), SEC24B (Proximity Label-MS), SEC24B (Proximity Label-MS)

ESM2 similar proteins: A1YFY6, A2T6X9, A6H7I8, B2RUJ5, F1M5F3, F1N2W9, O35430, O35431, O95487, O95628, O95644, P0C6S7, P14316, P17863, P22681, P22682, P23798, P23906, P35227, P81133, P98084, Q02410, Q0IHY4, Q13469, Q14190, Q14432, Q1L994, Q3UR85, Q52L14, Q5CD77, Q5RD33, Q60591, Q61045, Q61079, Q66JB6, Q69ZT9, Q6NRE7, Q6QB00, Q8BIZ1, Q8BT14

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
SEC24B	“form complex”	“COPII vesicle”	binding
SAR1A	“up-regulates quantity”	SEC24B	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 144 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
PD-L1(CD274) glycosylation and translocation to plasma membrane	5	24.0×	1e-04
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	7	21.8×	4e-06
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	5	18.2×	4e-04
EPHA-mediated growth cone collapse	5	17.6×	4e-04
EPH-ephrin mediated repulsion of cells	8	16.3×	4e-06
Cargo concentration in the ER	5	15.6×	7e-04
Maturation of spike protein	6	14.8×	2e-04
Constitutive Signaling by Aberrant PI3K in Cancer	12	14.1×	3e-08

GO biological processes:

GO term	Partners	Fold	FDR
COPII-coated vesicle cargo loading	5	38.7×	3e-05
peptidyl-tyrosine phosphorylation	10	32.9×	1e-10
cell surface receptor protein tyrosine kinase signaling pathway	15	20.4×	8e-13
ephrin receptor signaling pathway	6	16.1×	2e-04
protein autophosphorylation	14	15.9×	1e-10
protein N-linked glycosylation	5	10.3×	6e-03
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	9.9×	2e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	16	9.8×	2e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	175
Likely benign	14
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3912 predictions. Top by Δscore:

Variant	Effect	Δscore
4:109433998:GAACG:G	donor_gain	1.0000
4:109481672:TACA:T	acceptor_loss	1.0000
4:109481674:CAG:C	acceptor_loss	1.0000
4:109481675:A:AG	acceptor_gain	1.0000
4:109481675:A:AT	acceptor_loss	1.0000
4:109481676:G:GC	acceptor_gain	1.0000
4:109481676:GGC:G	acceptor_gain	1.0000
4:109481754:G:GT	donor_gain	1.0000
4:109481775:G:GT	donor_gain	1.0000
4:109491321:TTTTA:T	acceptor_loss	1.0000
4:109491324:TA:T	acceptor_loss	1.0000
4:109494610:TTTA:T	acceptor_loss	1.0000
4:109494613:A:AG	acceptor_gain	1.0000
4:109494614:G:GG	acceptor_gain	1.0000
4:109494614:GA:G	acceptor_gain	1.0000
4:109494614:GAT:G	acceptor_gain	1.0000
4:109494614:GATA:G	acceptor_gain	1.0000
4:109494614:GATAT:G	acceptor_gain	1.0000
4:109494734:GC:G	donor_gain	1.0000
4:109494822:ACCCG:A	donor_gain	1.0000
4:109494857:G:GG	donor_gain	1.0000
4:109500020:A:AG	donor_gain	1.0000
4:109500043:GAC:G	donor_gain	1.0000
4:109506312:T:TA	acceptor_gain	1.0000
4:109506315:A:AG	acceptor_gain	1.0000
4:109506315:ATT:A	acceptor_gain	1.0000
4:109506316:T:G	acceptor_gain	1.0000
4:109506317:T:A	acceptor_gain	1.0000
4:109506326:A:AG	acceptor_gain	1.0000
4:109506327:G:GG	acceptor_gain	1.0000

AlphaMissense

8168 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:109510080:G:A	G582E	1.000
4:109511985:T:A	I602N	1.000
4:109511990:A:G	R604G	1.000
4:109511991:G:C	R604T	1.000
4:109511991:G:T	R604M	1.000
4:109511992:G:C	R604S	1.000
4:109511992:G:T	R604S	1.000
4:109511993:T:A	C605S	1.000
4:109511993:T:C	C605R	1.000
4:109511994:G:A	C605Y	1.000
4:109511994:G:C	C605S	1.000
4:109511994:G:T	C605F	1.000
4:109511995:C:G	C605W	1.000
4:109512002:T:A	C608S	1.000
4:109512002:T:C	C608R	1.000
4:109512003:G:A	C608Y	1.000
4:109512003:G:C	C608S	1.000
4:109512003:G:T	C608F	1.000
4:109512004:T:G	C608W	1.000
4:109512006:G:C	R609P	1.000
4:109512011:T:C	Y611H	1.000
4:109512011:T:G	Y611D	1.000
4:109512015:T:A	I612N	1.000
4:109512019:C:A	N613K	1.000
4:109512019:C:G	N613K	1.000
4:109512050:T:A	W624R	1.000
4:109512050:T:C	W624R	1.000
4:109512051:G:C	W624S	1.000
4:109512052:G:C	W624C	1.000
4:109512052:G:T	W624C	1.000

dbSNP variants (sampled 300 via entrez): RS1000004125 (4:109446223 A>G), RS1000021036 (4:109459642 G>A,C), RS1000042464 (4:109536122 C>T), RS10000545 (4:109436722 G>C,T), RS10000561 (4:109492801 T>G), RS1000066049 (4:109502072 T>G), RS1000177097 (4:109453780 C>G,T), RS1000237369 (4:109470329 T>C), RS1000253060 (4:109495709 G>T), RS1000254927 (4:109452245 A>G), RS10002595 (4:109463782 T>C), RS1000272673 (4:109469996 A>T), RS1000342701 (4:109448475 A>G), RS10003981 (4:109533150 G>A), RS1000398339 (4:109465262 T>A)

Disease associations

OMIM: gene MIM:607184 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003815_62	Late-onset Alzheimer’s disease	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001870	late-onset Alzheimers disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
cobaltous chloride	increases expression	2
Arsenic Trioxide	affects cotreatment, affects expression, increases expression	2
Aflatoxin B1	decreases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
uranyl acetate	affects expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	decreases expression	1
kojic acid	increases expression	1
trichostatin A	affects expression, decreases reaction	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tetrabromobisphenol A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
nilotinib	affects cotreatment, affects expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TK45	HAP1 SEC24B (-) 1	Cancer cell line	Male
CVCL_TK46	HAP1 SEC24B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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