SEC23B

Summary

SEC23B (SEC23 homolog B, COPII component, HGNC:10702) is a protein-coding gene on chromosome 20p11.23, encoding Protein transport protein Sec23B (Q15437). 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 SEC23 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec23p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The function of this gene product has been implicated in cargo selection and concentration. Multiple alternatively spliced transcript variants have been identified in this gene.

Source: NCBI Gene 10483 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital dyserythropoietic anemia type 2 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 749 total — 44 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 78
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_006363

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10702
Approved symbol	SEC23B
Name	SEC23 homolog B, COPII component
Location	20p11.23
Locus type	gene with protein product
Status	Approved
Aliases	CDA-II, CDAII, HEMPAS
Ensembl gene	ENSG00000101310
Ensembl biotype	protein_coding
OMIM	610512
Entrez	10483

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 34 protein_coding, 1 retained_intron

ENST00000262544, ENST00000336714, ENST00000377465, ENST00000422877, ENST00000450074, ENST00000474619, ENST00000494645, ENST00000643747, ENST00000645851, ENST00000646240, ENST00000650089, ENST00000874272, ENST00000874273, ENST00000874274, ENST00000874275, ENST00000874276, ENST00000874277, ENST00000874278, ENST00000874279, ENST00000874280, ENST00000874281, ENST00000874282, ENST00000874283, ENST00000874284, ENST00000874285, ENST00000929133, ENST00000929134, ENST00000929135, ENST00000929136, ENST00000929137, ENST00000949712, ENST00000949713, ENST00000949714, ENST00000949715, ENST00000949716

RefSeq mRNA: 5 — MANE Select: NM_006363 NM_001172745, NM_001172746, NM_006363, NM_032985, NM_032986

CCDS: CCDS13137, CCDS86935

Canonical transcript exons

ENST00000650089 — 20 exons

Exon	Start	End
ENSE00000660167	18535653	18535742
ENSE00000660170	18545956	18546033
ENSE00000660171	18548609	18548770
ENSE00000660172	18551089	18551175
ENSE00000660173	18554235	18554390
ENSE00000859325	18532664	18532744
ENSE00000859326	18542296	18542402
ENSE00000859327	18543019	18543172
ENSE00000859328	18555108	18555173
ENSE00001474064	18560651	18561415
ENSE00001639307	18524433	18524669
ENSE00001702943	18527496	18527611
ENSE00001754392	18525788	18525932
ENSE00001770638	18524935	18525020
ENSE00001776346	18530680	18530803
ENSE00001792458	18515650	18515736
ENSE00002407714	18510822	18511056
ENSE00003651350	18512225	18512282
ENSE00003787525	18526373	18526531
ENSE00003838689	18507940	18507972

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 97.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.9322 / max 312.3113, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183690	41.1472	1819
183688	7.4726	1716
183689	0.3124	142

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.65	gold quality
islet of Langerhans	UBERON:0000006	96.87	gold quality
parotid gland	UBERON:0001831	96.34	gold quality
epithelium of nasopharynx	UBERON:0001951	95.78	gold quality
nasopharynx	UBERON:0001728	95.77	gold quality
pancreas	UBERON:0001264	95.57	gold quality
body of pancreas	UBERON:0001150	95.49	gold quality
sperm	CL:0000019	95.28	gold quality
right adrenal gland	UBERON:0001233	94.53	gold quality
bronchial epithelial cell	CL:0002328	94.33	gold quality
right adrenal gland cortex	UBERON:0035827	94.20	gold quality
adenohypophysis	UBERON:0002196	94.11	gold quality
oocyte	CL:0000023	94.05	gold quality
pituitary gland	UBERON:0000007	93.83	gold quality
pigmented layer of retina	UBERON:0001782	93.78	gold quality
retina	UBERON:0000966	93.76	gold quality
lower lobe of lung	UBERON:0008949	93.67	gold quality
left adrenal gland	UBERON:0001234	93.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.33	gold quality
corpus epididymis	UBERON:0004359	93.27	gold quality
choroid plexus epithelium	UBERON:0003911	93.20	gold quality
adrenal gland	UBERON:0002369	93.18	gold quality
tonsil	UBERON:0002372	93.11	gold quality
adrenal cortex	UBERON:0001235	93.06	gold quality
esophagus squamous epithelium	UBERON:0006920	92.93	gold quality
bone marrow cell	CL:0002092	92.92	gold quality
left adrenal gland cortex	UBERON:0035825	92.89	gold quality
ganglionic eminence	UBERON:0004023	92.69	gold quality
germinal epithelium of ovary	UBERON:0001304	92.59	gold quality
oral cavity	UBERON:0000167	92.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

47 targeting SEC23B, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-651-5P	99.64	68.49	1104

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 32)

• Hetero- or homozygous mutation of CDAN2 causes hypoglycosylation of band 3, accumulation and hypoglycosylation of polyglycosylceramides, and accumulation of lactotriaosylceramide. (PMID:11836161)
• These results provide in vivo evidence for SEC23B selectivity in erythroid differentiation and show that SEC23A and SEC23B, although highly related paralogous secretory COPII components, are nonredundant in erythrocyte maturation. (PMID:19561605)
• Congenital dyserythropoietic anemia type II (CDAII) is caused by mutations in the SEC23B gene. (PMID:19621418)
• Correlation between SEC23B mutations and congenital dyserythropoietic anemia type II parameters shows that addition of one missense mutation and one nonsense mutation tends to produce a more severe presentation then association of two missense mutations. (PMID:20015893)
• This study found SEC23B mutations in two patients previously classified as atypical congenital dyserythropoietic anemias presenting with hydrops foetalis. (PMID:20381388)
• found 19 novel variants in the homozygous or the compound heterozygous state in 28 CDA II patients from 21 unrelated families enrolled in the CDA II International Registry (PMID:20941788)
• Most congenital dyserythropoietic anemia II patients in Israel are of Moroccan Jewish origin and carry a common SEC23B mutation, E109K, the first to be described as a founder mutation causing CDA II. (PMID:21252497)
• Data indicate that SEC23B founder mutations E109K and R14W account for about 54% of all mutations in CDA II patients in Italy; data suggest R14W occurred Southern Italy, E109K is more widespread within Europe. (PMID:21850656)
• study identified four novel SEC23B mutations associated with ongenital dyserythropoietic anemia type II disease; also demonstrated that the genetic alteration results in a significant decrease of SEC23B transcript in erythroid precursors (PMID:22208203)
• Mutations in SEC23B lead to congenital dyserythropoietic anemia type II due to alterations in coat protein (COP)II complex trafficking machinery. [REVIEW] (PMID:22764119)
• ALG-2 attenuates COPII budding in vitro and stabilizes the Sec23/Sec31A complex. (PMID:24069399)
• Both probands with congenital dyserythropoietic anemia IotaI in the second family were homozygotes of the SEC23B gene with mutation c.938G>A (R313H). (PMID:24196372)
• Congenital dyserythropoietic anemia, type II with SEC23B exon 12 c.1385 A –> G mutation, and pseudo-Gaucher cells in two siblings has been described. (PMID:24801240)
• SEC23B-Y462C congenital dyserythropoietic anemia type II is only seen in a distinct Indian community (Vaish) in whom a recessively inherited shared haplotype can be showed, consistent with a founder effect. (PMID:25418799)
• Germline Heterozygous Variants in SEC23B Are Associated with Cowden Syndrome and Enriched in Apparently Sporadic Thyroid Cancer. (PMID:26522472)
• miR-130a is an epigenetically regulated miRNA involved in regulation of key molecular and phenotypic features of prostate carcinogenesis, acting as a tumour suppressor miRNA by targeting SEC23B and DEPDC1. (PMID:27984115)
• described the functional interaction between GATA1 and SEC23B genes in two patients with suspected congenital dyserythropoietic anemia type II (PMID:28550189)
• A Y462C mutation was found in 5 members of a consanguineous Indian family. In the homozygous patient, it resulted in congenital dyserythropoietic anemia type II. (PMID:28879554)
• Mutation in SEC23B gene is associated with congenital dyserythropoietic anemia. (PMID:29031773)
• novel compound mutations of c.1727T>C and c.1831C>T of the SEC23B gene probably underlie the congenital dyserythropoietic anemia type II in the family (PMID:29188620)
• mutant SEC23B binds to UBF transcription factor, with increased UBF transcription factor binding at the ribosomal DNA promoter. Our data indicate SEC23B has potential non-canonical COPII-independent function, particularly within the ribosome biogenesis pathway, and that may contribute to the pathogenesis of cancer-predisposition. (PMID:29893852)
• these data demonstrate an equivalent function for SEC23A/B, with evolutionary shifts in the transcription program likely accounting for the distinct phenotypes of SEC23A/B deficiency within and across species, a paradigm potentially applicable to other sets of paralogous genes. (PMID:30065114)
• Here, the authors show that the F-box protein FBXW5 targets SEC23B, a component of COPII, for proteasomal degradation and that this event limits the autophagic flux in the presence of nutrients. In response to starvation, ULK1 phosphorylates SEC23B on Serine 186, preventing the interaction of SEC23B with FBXW5 and, therefore, inhibiting SEC23B degradation. (PMID:30596474)
• Mutations in the coat complex II component SEC23B promote colorectal cancer metastasis. (PMID:32123160)
• RAP-011 Rescues the Disease Phenotype in a Cellular Model of Congenital Dyserythropoietic Anemia Type II by Inhibiting the SMAD2-3 Pathway. (PMID:32759740)
• Non-canonical role of wild-type SEC23B in the cellular stress response pathway. (PMID:33753724)
• Compound heterozygosity for two novel mutations of the SEC23B gene in congenital dyserythropoietic anemia type II. (PMID:33914262)
• [Variant analysis of SEC23B gene in 4 families with congenital dyserythropoietic anemia]. (PMID:34365611)
• A common human missense mutation of vesicle coat protein SEC23B leads to growth restriction and chronic pancreatitis in mice. (PMID:34954140)
• SEC23B Loss-of-Function Suppresses Hepcidin Expression by Impairing Glycosylation Pathway in Human Hepatic Cells. (PMID:35163229)
• Congenital Dyserythropoietic Anemia Type II: High Prevalence of c.1385A>G, (p.Tyr462Cys) Mutation in the Indian Population. (PMID:37204595)
• New Cases and Mutations in SEC23B Gene Causing Congenital Dyserythropoietic Anemia Type II. (PMID:37373084)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sec23b	ENSDARG00000019360
mus_musculus	Sec23b	ENSMUSG00000027429
rattus_norvegicus	Sec23b	ENSRNOG00000008411
drosophila_melanogaster	Sec23	FBGN0262125
caenorhabditis_elegans		WBGENE00004754

Paralogs (1): SEC23A (ENSG00000100934)

Protein

Protein identifiers

Protein transport protein Sec23B — Q15437 (reviewed: Q15437)

Alternative names: SEC23-related protein B

All UniProt accessions (7): Q15437, A0A2R8Y633, A0A2R8Y7S7, A0A2R8YF30, A0A2R8YFH5, Q5QPE1, Q5QPE2

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.

Subunit / interactions. COPII is composed of at least five proteins: the Sec23/24 complex, the Sec13/31 complex and Sar1. Interacts with SAR1A.

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

Tissue specificity. Ubiquitously expressed.

Disease relevance. Cowden syndrome 7 (CWS7) [MIM:616858] A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. CWS7 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Anemia, congenital dyserythropoietic, 2 (CDAN2) [MIM:224100] An autosomal recessive blood disorder characterized by morphological abnormalities of erythroblasts, ineffective erythropoiesis, normocytic anemia, iron overload, jaundice, and variable splenomegaly. Ultrastructural features include bi- or multinucleated erythroblasts in bone marrow, karyorrhexis, and the presence of Gaucher-like bone marrow histiocytes. The main biochemical feature of the disease is defective glycosylation of some red blood cells membrane proteins. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (5): NP_001166216, NP_001166217, NP_006354, NP_116780, NP_116781 (=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
IPR037364	Sec23	Family
IPR037550	Sec23_C	Domain

Pfam: PF00626, PF04810, PF04811, PF04815, PF08033

UniProt features (31 total): sequence variant 22, binding site 4, modified residue 2, initiator methionine 1, chain 1, repeat 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15437-F1	92.41	0.87

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): 61; 66; 85; 88

Post-translational modifications (2): 2, 564

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 370 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, SHEPARD_CRASH_AND_BURN_MUTANT_UP, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, BROWNE_HCMV_INFECTION_24HR_UP, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOCC_COATED_VESICLE, GOCC_VESICLE_COAT, CCCNNNNNNAAGWT_UNKNOWN, MODULE_98, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, GOBP_MEMBRANE_ORGANIZATION, YY1_01

GO Biological Process (6): intracellular protein transport (GO:0006886), COPII-coated vesicle cargo loading (GO:0090110), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), COPII-coated vesicle budding (GO:0090114)

GO Molecular Function (4): GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (11): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), endomembrane system (GO:0012505), COPII vesicle coat (GO:0030127), perinuclear region of cytoplasm (GO:0048471), endoplasmic reticulum exit site (GO:0070971), cytoplasm (GO:0005737), ER to Golgi transport vesicle membrane (GO:0012507), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	5
intracellular transport	3
intracellular protein localization	2
transport	2
protein transport	1
vesicle cargo loading	1
COPII-coated vesicle budding	1
intercellular transport	1
Golgi vesicle transport	1
establishment of protein localization	1
cellular process	1
endoplasmic reticulum to Golgi vesicle-mediated transport	1
vesicle budding from membrane	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vacuole	1
plasma membrane	1
ER to Golgi transport vesicle membrane	1
vesicle coat	1
endoplasmic reticulum	1
intracellular anatomical structure	1
COPII-coated ER to Golgi transport vesicle	1
transport vesicle membrane	1
coated vesicle membrane	1
intracellular vesicle	1

Protein interactions and networks

STRING

1980 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEC23B	CDAN1	Q8IWY9	945
SEC23B	SEC24A	O95486	854
SEC23B	TRAPPC3	O43617	846
SEC23B	SAR1A	Q9NR31	844
SEC23B	SEC31A	O94979	801
SEC23B	SEC13	P55735	800
SEC23B	SAR1B	Q9Y6B6	799
SEC23B	GOLPH3	Q9H4A6	781
SEC23B	PREB	Q9HCU5	770
SEC23B	KLF1	Q13351	741
SEC23B	CDIN1	Q9Y2V0	723
SEC23B	SEC16A	O15027	722
SEC23B	SEC24D	O94855	711
SEC23B	SEC24C	P53992	668
SEC23B	SCIN	Q9Y6U3	628

IntAct

169 interactions, top by confidence:

A	B	Type	Score
EIF4A3	CASC3	psi-mi:“MI:0914”(association)	0.980
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
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
SEC24C	SEC23B	psi-mi:“MI:0915”(physical association)	0.800
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SEC24D	SEC23A	psi-mi:“MI:0914”(association)	0.690
HOXA3	SEC23B	psi-mi:“MI:0915”(physical association)	0.670
SEC23B	HOXA3	psi-mi:“MI:0915”(physical association)	0.670
SEC23A	SEC23B	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
SEC23B	SEC24A	psi-mi:“MI:0914”(association)	0.640
BOL3	SEC23B	psi-mi:“MI:0915”(physical association)	0.610
SEC23B	BOL3	psi-mi:“MI:0915”(physical association)	0.610

BioGRID (311): SEC23B (Two-hybrid), SEC23B (Two-hybrid), SEC23B (Two-hybrid), CPSF7 (Two-hybrid), FATE1 (Two-hybrid), DTX2 (Two-hybrid), PRRC1 (Two-hybrid), SYNE4 (Two-hybrid), SEC23B (Affinity Capture-MS), SEC23B (Affinity Capture-MS), SEC23B (Two-hybrid), SEC23B (Two-hybrid), CPNE2 (Co-fractionation), SEC13 (Co-fractionation), SEC23B (Co-fractionation)

ESM2 similar proteins: A2VDL8, A7YWS7, O35142, O54956, O55029, O70133, O88544, O94973, O95782, P17426, P17427, P18484, P35605, P35606, P38024, P48444, P53619, P56282, Q01405, Q05AS9, Q08211, Q0VCK5, Q15436, Q15437, Q28141, Q3SZA0, Q3SZN2, Q41141, Q4R4I8, Q5E9U9, Q5F418, Q5R5G2, Q5R664, Q5R874, Q5R9P3, Q5RA77, Q5XJY5, Q5ZK03, Q5ZKQ6, Q5ZL57

Diamond homologs: A1CRW7, A1D4S4, A2Q8L1, A2VDL8, A3GFA2, A4R1J7, A5DA00, A5E7S3, O74873, O94672, P0CR38, P0CR39, P15303, Q01405, Q05AS9, Q0CUU1, Q0US25, Q15436, Q15437, Q1DY01, Q2HB00, Q2URM9, Q3SZN2, Q4PE39, Q4WK80, Q54T59, Q5A455, Q5BGR9, Q5R5G2, Q5R9P3, Q5ZK03, Q6BQT6, Q6C5L5, Q6CPH3, Q6FSI6, Q6FSK3, Q758M7, Q7SZE5, Q84WI4, Q8H0S3

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
ULK1	“up-regulates quantity by stabilization”	SEC23B	phosphorylation
FBXW5	“down-regulates quantity by destabilization”	SEC23B	ubiquitination
SEC23B	“form complex”	“COPII vesicle”	binding
SEC23IP	“up-regulates activity”	SEC23B	binding
SAR1A	“up-regulates quantity”	SEC23B	binding
SEC23B	unknown	UBA52	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 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
Activation of BAD and translocation to mitochondria	5	35.2×	1e-05
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	31.1×	2e-05
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	31.1×	2e-05
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	7	25.5×	1e-06
Activation of BH3-only proteins	5	23.0×	7e-05
EPHA-mediated growth cone collapse	6	21.1×	2e-05
EPH-ephrin mediated repulsion of cells	10	20.3×	2e-08
Cargo concentration in the ER	5	15.6×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
COPII-coated vesicle cargo loading	6	47.6×	6e-07
peptidyl-tyrosine phosphorylation	8	27.0×	2e-07
ephrin receptor signaling pathway	8	22.0×	7e-07
cell surface receptor protein tyrosine kinase signaling pathway	12	16.7×	9e-09
positive regulation of G1/S transition of mitotic cell cycle	5	16.1×	1e-03
protein targeting	5	14.7×	2e-03
protein autophosphorylation	12	13.9×	4e-08
insulin receptor signaling pathway	7	12.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	44
Likely pathogenic	31
Uncertain significance	193
Likely benign	327
Benign	62

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1176123	GRCh37/hg19 20p11.23(chr20:18492869-18496380)x1	Pathogenic
1222	NM_006363.6(SEC23B):c.325G>A (p.Glu109Lys)	Pathogenic
1225	NM_006363.6(SEC23B):c.790C>T (p.Arg264Ter)	Pathogenic
1358676	NM_006363.6(SEC23B):c.1603C>T (p.Arg535Ter)	Pathogenic
167667	NM_006363.6(SEC23B):c.1489C>T (p.Arg497Cys)	Pathogenic
167668	NM_006363.6(SEC23B):c.1648C>T (p.Arg550Ter)	Pathogenic
1806373	NM_006363.6(SEC23B):c.640C>T (p.Gln214Ter)	Pathogenic
2199307	NM_006363.6(SEC23B):c.1909del (p.Val637fs)	Pathogenic
2690492	NM_006363.6(SEC23B):c.1753del (p.His585fs)	Pathogenic
2921892	NM_006363.6(SEC23B):c.1402C>T (p.Gln468Ter)	Pathogenic
2921906	NM_006363.6(SEC23B):c.2190_2191dup (p.Asn731fs)	Pathogenic
2922469	NM_006363.6(SEC23B):c.873del (p.Phe291fs)	Pathogenic
2923149	NM_006363.6(SEC23B):c.235C>T (p.Arg79Ter)	Pathogenic
2924090	NC_000020.11:g.18512225_18512228del	Pathogenic
2925278	NM_006363.6(SEC23B):c.1015C>T (p.Arg339Ter)	Pathogenic
2925649	NM_006363.6(SEC23B):c.1129_1130del (p.Asp377fs)	Pathogenic
2925651	NM_006363.6(SEC23B):c.1989dup (p.Glu664Ter)	Pathogenic
2925652	NM_006363.6(SEC23B):c.2152C>T (p.Arg718Ter)	Pathogenic
2932853	NM_006363.6(SEC23B):c.1741C>T (p.Gln581Ter)	Pathogenic
2939496	NM_006363.6(SEC23B):c.2212C>T (p.Gln738Ter)	Pathogenic
2940684	NM_006363.6(SEC23B):c.249G>A (p.Trp83Ter)	Pathogenic
2943473	NM_006363.6(SEC23B):c.545del (p.Gly182fs)	Pathogenic
2945496	NM_006363.6(SEC23B):c.983dup (p.Ala329fs)	Pathogenic
2946593	NM_006363.6(SEC23B):c.2202T>A (p.Tyr734Ter)	Pathogenic
2948437	NM_006363.6(SEC23B):c.1831del (p.Arg611fs)	Pathogenic
2950689	NM_006363.6(SEC23B):c.1660C>T (p.Arg554Ter)	Pathogenic
2951473	NM_006363.6(SEC23B):c.337del (p.Gln113fs)	Pathogenic
2953423	NM_006363.6(SEC23B):c.584dup (p.Leu195fs)	Pathogenic
3248266	NC_000020.10:g.(?18522920)(18523066_?)del	Pathogenic
3248269	NC_000020.10:g.(?18491480)(18535837_?)del	Pathogenic

SpliceAI

3518 predictions. Top by Δscore:

Variant	Effect	Δscore
20:18512223:A:AG	acceptor_gain	1.0000
20:18512224:G:GG	acceptor_gain	1.0000
20:18512224:GT:G	acceptor_gain	1.0000
20:18512224:GTCA:G	acceptor_gain	1.0000
20:18515648:A:AG	acceptor_gain	1.0000
20:18515649:G:GT	acceptor_gain	1.0000
20:18515649:GT:G	acceptor_gain	1.0000
20:18515649:GTT:G	acceptor_gain	1.0000
20:18515649:GTTT:G	acceptor_gain	1.0000
20:18515649:GTTTC:G	acceptor_gain	1.0000
20:18515724:G:GG	donor_gain	1.0000
20:18515733:ACAG:A	donor_loss	1.0000
20:18515734:CAGG:C	donor_loss	1.0000
20:18515735:AGGTA:A	donor_loss	1.0000
20:18515736:GGTA:G	donor_loss	1.0000
20:18515737:G:C	donor_loss	1.0000
20:18515738:T:G	donor_loss	1.0000
20:18524424:T:TA	acceptor_gain	1.0000
20:18524429:A:AG	acceptor_gain	1.0000
20:18524429:AAAGC:A	acceptor_gain	1.0000
20:18524430:A:G	acceptor_gain	1.0000
20:18524432:GC:G	acceptor_gain	1.0000
20:18524464:AT:A	acceptor_gain	1.0000
20:18524464:ATGT:A	acceptor_gain	1.0000
20:18524464:ATGTG:A	acceptor_gain	1.0000
20:18524465:T:G	acceptor_gain	1.0000
20:18524465:T:TA	acceptor_gain	1.0000
20:18524467:T:TA	acceptor_gain	1.0000
20:18524468:G:A	acceptor_gain	1.0000
20:18524476:C:G	acceptor_gain	1.0000

AlphaMissense

5042 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:18512250:T:A	W83R	1.000
20:18512250:T:C	W83R	1.000
20:18535680:T:A	W448R	1.000
20:18535680:T:C	W448R	1.000
20:18548615:T:C	F584L	1.000
20:18548617:C:A	F584L	1.000
20:18548617:C:G	F584L	1.000
20:18548618:C:G	H585D	1.000
20:18548622:T:C	L586P	1.000
20:18548625:G:C	R587T	1.000
20:18548625:G:T	R587I	1.000
20:18548626:A:C	R587S	1.000
20:18548626:A:T	R587S	1.000
20:18548628:G:C	R588T	1.000
20:18548628:G:T	R588I	1.000
20:18548629:A:C	R588S	1.000
20:18548629:A:T	R588S	1.000
20:18548663:G:C	D600H	1.000
20:18551135:T:C	L651P	1.000
20:18555118:T:A	L720H	1.000
20:18555134:C:A	N725K	1.000
20:18555134:C:G	N725K	1.000
20:18555136:C:A	P726Q	1.000
20:18560673:C:T	T746I	1.000
20:18560696:T:C	F754L	1.000
20:18560698:C:A	F754L	1.000
20:18560698:C:G	F754L	1.000
20:18510893:A:C	S20R	0.999
20:18510895:T:A	S20R	0.999
20:18510895:T:G	S20R	0.999

dbSNP variants (sampled 300 via entrez): RS1000005964 (20:18522909 A>T), RS1000048974 (20:18545610 A>G), RS1000056684 (20:18522724 G>A), RS1000103617 (20:18540188 T>C), RS1000167167 (20:18527378 A>C,T), RS1000194071 (20:18542439 A>G), RS1000313213 (20:18534786 T>C), RS1000327231 (20:18535915 C>T), RS1000445034 (20:18536154 C>T), RS1000472633 (20:18512883 C>T), RS1000524038 (20:18557810 T>C), RS1000526689 (20:18517351 A>G), RS1000615702 (20:18516375 C>T), RS1000621926 (20:18555346 G>A), RS1000712536 (20:18542825 A>G)

Disease associations

OMIM: gene MIM:610512 | disease phenotypes: MIM:224100, MIM:616858, MIM:224120

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital dyserythropoietic anemia type 2	Definitive	Autosomal recessive
Cowden disease	Supportive	Autosomal dominant
congenital dyserythropoietic anemia	Limited	Autosomal recessive
Cowden syndrome 7	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital dyserythropoietic anemia type 2	Definitive	AR

Mondo (5): congenital dyserythropoietic anemia type 2 (MONDO:0009134), Cowden syndrome 7 (MONDO:0014802), hereditary ataxia (MONDO:0100309), congenital dyserythropoietic anemia (MONDO:0019403), Cowden disease (MONDO:0016063)

Orphanet (4): Cowden syndrome (Orphanet:201), Congenital dyserythropoietic anemia type II (Orphanet:98873), Hereditary ataxia (Orphanet:183518), Congenital dyserythropoietic anemia (Orphanet:85)

HPO phenotypes

78 total (30 of 78 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000036	Abnormal penis morphology
HP:0000077	Abnormality of the kidney
HP:0000130	Abnormality of the uterus
HP:0000158	Macroglossia
HP:0000218	High palate
HP:0000221	Furrowed tongue
HP:0000256	Macrocephaly
HP:0000365	Hearing impairment
HP:0000518	Cataract
HP:0000545	Myopia
HP:0000717	Autism
HP:0000767	Pectus excavatum
HP:0000771	Gynecomastia
HP:0000820	Abnormality of the thyroid gland
HP:0000853	Goiter
HP:0000872	Hashimoto thyroiditis
HP:0000952	Jaundice
HP:0000982	Palmoplantar keratoderma
HP:0000995	Melanocytic nevus
HP:0001028	Hemangioma
HP:0001048	Cavernous hemangioma
HP:0001053	Hypopigmented skin patches
HP:0001081	Cholelithiasis
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001263	Global developmental delay

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_62	Refractive error	2.000000e-08

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000742	Anemia, Dyserythropoietic, Congenital	C15.378.050.141.150.095; C16.320.070.095
D006223	Hamartoma Syndrome, Multiple	C04.445.435; C04.651.435; C04.700.435; C16.320.700.435
C531684	Hereditary spinal ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066275 (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
7.40	Kd	39.67	nM	CHEMBL5653589
7.40	ED50	39.67	nM	CHEMBL5653589
5.03	Kd	9392	nM	CHEMBL3752910
5.03	ED50	9392	nM	CHEMBL3752910

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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149364: Binding affinity to human SEC23B incubated for 45 mins by Kinobead based pull down assay	kd	0.0397	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149364: Binding affinity to human SEC23B incubated for 45 mins by Kinobead based pull down assay	kd	9.3920	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	4
bisphenol A	affects expression, decreases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
sodium arsenite	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
bisphenol F	affects cotreatment, decreases expression	1
urushiol	increases expression	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
lead acetate	affects cotreatment, decreases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, increases reaction	1
zinc protoporphyrin	affects cotreatment, decreases expression	1
cobaltous chloride	decreases expression	1
nickel sulfate	decreases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases 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
LDN 193189	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, 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
CHEMBL5652406	Binding	Binding affinity to human SEC23B 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

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

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

Cellosaurus	Name	Category	Sex
CVCL_A9Y2	B-LCL-CDG4	Transformed cell line	Female
CVCL_A9Y3	B-LCL-CDG7	Transformed cell line	Male
CVCL_TK38	HAP1 SEC23B (-) 1	Cancer cell line	Male
CVCL_TK39	HAP1 SEC23B (-) 2	Cancer cell line	Male
CVCL_TK40	HAP1 SEC23B (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03306446	PHASE4	UNKNOWN	Changing the coUrse of cRohn’s Disease With an Early Use of Adalimumab
NCT00971789	PHASE2	COMPLETED	Sirolimus to Treat Cowden Syndrome and Other PTEN Hamartomatous Tumor Syndromes
NCT04094675	PHASE2	COMPLETED	Sirolimus for Cowden Syndrome With Colon Polyposis
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00620594	PHASE1	COMPLETED	A Phase I/II Study of BEZ235 in Patients With Advanced Solid Malignancies Enriched by Patients With Advanced Breast Cancer
NCT01757964	PHASE1	COMPLETED	Bacteriotherapy in Pediatric Inflammatory Bowel Disease
NCT07471516	PHASE1/PHASE2	RECRUITING	Zoledronic Acid Treatment in Patients With Congenital Dyserythropoietic Anemia
NCT02964494	Not specified	RECRUITING	The Congenital Dyserythropoietic Anemia Registry (CDAR)
NCT03983629	Not specified	UNKNOWN	Registry of Congenital Dyserythropoietic Anemia
NCT06213402	Not specified	RECRUITING	RADeep Multicenter European Epidemiological Platform for Patients Diagnosed With Rare Anemia Disorders (RADs)
NCT07206095	Not specified	RECRUITING	Integrative Diagnosis for SCD and Other RADs
NCT07218575	PHASE2/PHASE3	NOT_YET_RECRUITING	Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations
NCT00600275	PHASE1/PHASE2	COMPLETED	A Phase I/II Study of BGT226 in Adult Patients With Advanced Solid Malignancies Including Patients With Advanced Breast Cancer
NCT02856763	Not specified	COMPLETED	Predictive Factors of ANTI-TNF Response in Luminal Crohn’s Disease Complicated by Abscess
NCT03487900	Not specified	UNKNOWN	Is the Endoscopic Remission Evaluation, Using the CREDO 1 Index / Score in CD Patients in Clinical Remission at Baseline, Predictive of Sustained Clinical Remission Using a 2-year Follow up
NCT03498625	Not specified	COMPLETED	Crohn’s Disease Endoscopic REmission Definition in an Objective Way
NCT03702309	Not specified	RECRUITING	Liquid Biopsy Evaluation and Repository Development at Princess Margaret
NCT06163365	Not specified	UNKNOWN	Inherited Cancer Early Diagnosis (ICED) Study
NCT06523582	Not specified	RECRUITING	Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients
NCT01360164	PHASE1/PHASE2	UNKNOWN	Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Therapy for Patients With Hereditary Ataxia
NCT00004306	Not specified	COMPLETED	Clinical and Molecular Correlations in Spinocerebellar Ataxia Type 10 (SCA10)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04750850	Not specified	COMPLETED	Core Stability Exercises and Hereditary Ataxia
NCT05160870	Not specified	UNKNOWN	Genotype-phenotype Correlation and Pathogenic Mechanism in Hereditary Ataxia
NCT05160883	Not specified	UNKNOWN	Neuroimaging Changes in Hereditary Ataxia
NCT06034886	Not specified	AVAILABLE	Expanded Access Protocol of Troriluzole in Patients With Spinocerebellar Ataxia (SCA)
NCT06152133	Not specified	COMPLETED	Telerehabilitation, Core Stability Exercises and Hereditary Ataxia (TRCore-ataxia)
NCT06267222	Not specified	ENROLLING_BY_INVITATION	Trans-spinal Electrical Stimulation in Individuals With Spinocerebellar Ataxia
NCT07092358	Not specified	RECRUITING	Hereditary Ataxia Research on Multi-Omics and Neuroclinical Insights in the Yangtze Delta
NCT07200505	Not specified	NOT_YET_RECRUITING	Telerehabilitation for Core Stability and Strength in Hereditary Ataxia