SEC23B

SEC23 homolog B, COPII coat complex component, the group of COPII coat complex

Basic information

Region (hg38): 20:18507520-18561415

Previous symbols: [ "CDAN2" ]

Links

ENSG00000101310 ∙ NCBI:10483 ∙ OMIM:610512 ∙ HGNC:10702 ∙ Uniprot:Q15437 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital dyserythropoietic anemia type 2 (Definitive), mode of inheritance: AR
• congenital dyserythropoietic anemia (Limited), mode of inheritance: AR
• congenital dyserythropoietic anemia type 2 (Strong), mode of inheritance: AR
• Cowden disease (Supportive), mode of inheritance: AD
• congenital dyserythropoietic anemia type 2 (Supportive), mode of inheritance: AR
• Cowden syndrome 7 (Limited), mode of inheritance: AD
• congenital dyserythropoietic anemia type 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cowden syndrome 7; Anemia, dyserythropoietic congenital, type II	AD/AR	Gastrointestinal; Hematologic; Oncologic	Individuals with Cowden syndrome have been described with cancer, and awareness may be beneficial to allow screening, prompt diagnosis, and management; Individuals with Anemia, dyserythropoietic congenital, type II may require RBC transfusions in the neonatal period; Splenectomy may be beneficial; Gallbladder complications are common, and early treatment may be beneficial; Iron overload is common	Endocrine; Gastrointestinal; Hematologic; Oncologic	13884336; 5807784; 5807786; 4340898; 10753261; 11493480; 19621418; 19561605; 20381388; 20941788;21252497; 21378561; 21850656; 22208203; 22428539; 23065504; 23453696; 23940284; 23978024; 24196372; 26522472
Heterozygotes with variants related to Anemia, dyserythropoietic congenital, type II may have mild manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEC23B gene.

• Congenital dyserythropoietic anemia, type II;Cowden syndrome 7 (26 variants)
• Cowden syndrome 7;Congenital dyserythropoietic anemia, type II (16 variants)
• not provided (11 variants)
• Congenital dyserythropoietic anemia, type II (9 variants)
• Cowden syndrome 7 (1 variants)
• SEC23B-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEC23B gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	164	3	169
missense	4	4	113	9	2	132
nonsense	21	2				23
start loss						0
frameshift	16	7	1			24
inframe indel			1			1
splice donor/acceptor (+/-2bp)	4	10	1	1		16
splice region		1	4	35	5	45
non coding			20	123	57	200
Total	45	23	138	297	62

Highest pathogenic variant AF is 0.000243

Variants in SEC23B

This is a list of pathogenic ClinVar variants found in the SEC23B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-18507593-A-C		Congenital dyserythropoietic anemia	Uncertain significance (Jun 14, 2016)
20-18507686-G-A		Congenital dyserythropoietic anemia	Uncertain significance (Jun 14, 2016)
20-18507704-C-T		Congenital dyserythropoietic anemia	Uncertain significance (Jun 14, 2016)
20-18507755-C-G		Congenital dyserythropoietic anemia	Benign (Jul 27, 2018)
20-18507801-G-T		Congenital dyserythropoietic anemia	Uncertain significance (Jun 14, 2016)
20-18507893-C-G		Congenital dyserythropoietic anemia	Uncertain significance (Jun 14, 2016)
20-18507907-G-A		Congenital dyserythropoietic anemia	Uncertain significance (Jun 14, 2016)
20-18507911-G-C		Congenital dyserythropoietic anemia	Uncertain significance (Jun 14, 2016)
20-18507930-G-C		Congenital dyserythropoietic anemia	Likely benign (Jun 14, 2016)
20-18507935-T-G		Congenital dyserythropoietic anemia	Uncertain significance (Jun 14, 2016)
20-18507963-C-T		Congenital dyserythropoietic anemia, type II	Benign (Jan 13, 2018)
20-18508031-G-A			Uncertain significance (Dec 01, 2020)
20-18508110-G-C			Benign (Jul 27, 2018)
20-18508193-G-C			Likely benign (Jun 17, 2019)
20-18510821-G-A		Congenital dyserythropoietic anemia, type II	Uncertain significance (Dec 16, 2019)
20-18510828-T-C		Congenital dyserythropoietic anemia, type II	Uncertain significance (Jan 13, 2018)
20-18510840-C-T		Congenital dyserythropoietic anemia, type II;Cowden syndrome 7	Uncertain significance (Apr 11, 2022)
20-18510841-G-A		Congenital dyserythropoietic anemia, type II;Cowden syndrome 7	Likely benign (Dec 11, 2023)
20-18510844-A-G		Congenital dyserythropoietic anemia, type II;Cowden syndrome 7	Likely benign (Dec 18, 2023)
20-18510859-C-A		Congenital dyserythropoietic anemia, type II;Cowden syndrome 7	Likely benign (Mar 08, 2023)
20-18510859-C-T		Congenital dyserythropoietic anemia, type II;Cowden syndrome 7	Likely benign (Oct 15, 2023)
20-18510875-C-T		Congenital dyserythropoietic anemia, type II • Congenital dyserythropoietic anemia, type II;Cowden syndrome 7 • SEC23B-related disorder	Pathogenic/Likely pathogenic (Aug 01, 2024)
20-18510888-G-A		Congenital dyserythropoietic anemia, type II;Cowden syndrome 7 • not specified	Conflicting classifications of pathogenicity (Mar 22, 2024)
20-18510899-A-G			Uncertain significance (Jul 01, 2022)
20-18510901-C-A			Uncertain significance (Mar 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEC23B	protein_coding	protein_coding	ENST00000336714	19	53923

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.10e-20	0.282	125574	0	174	125748	0.000692

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.473	390	417	0.935	0.0000234	5029
Missense in Polyphen		105	128.73	0.81568		1496
Synonymous	0.291	145	150	0.970	0.00000826	1510
Loss of Function	1.68	37	49.8	0.743	0.00000329	486

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000830	0.000828
Ashkenazi Jewish	0.00	0.00
East Asian	0.000544	0.000544
Finnish	0.000416	0.000416
European (Non-Finnish)	0.000951	0.000932
Middle Eastern	0.000544	0.000544
South Asian	0.000719	0.000719
Other	0.000655	0.000652

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000250|UniProtKB:Q15436}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:19561605, ECO:0000269|PubMed:19621418}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);Sterol Regulatory Element-Binding Proteins (SREBP) signalling (Consensus)

Recessive Scores

• pRec: 0.152

Intolerance Scores

• loftool: 0.120
• rvis_EVS: 0.49
• rvis_percentile_EVS: 79.61

Haploinsufficiency Scores

• pHI: 0.104
• hipred: N
• hipred_score: 0.333
• ghis: 0.554

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.738

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sec23b
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; immune system phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: sec23b
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: immature

Gene ontology

• Biological process: intracellular protein transport;positive regulation of GTPase activity;COPII-coated vesicle cargo loading
• Cellular component: Golgi membrane;endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;endomembrane system;COPII vesicle coat;endoplasmic reticulum exit site
• Molecular function: GTPase activator activity;protein binding