SEC23B
protein-codingSEC23 homolog B, COPII coat complex component, the group of COPII coat complex
Gene summary
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. [provided by RefSeq, Feb 2010]
- CDAN2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~53.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009134
Submitter: ClinGen
SEC23B was first reported in relation to autosomal recessive congenital dyserythropoietic anemia II (CDANII) in 2009 (Bianchi et al. (PMID: 19621418) & Schwarz et al. (PMID:19561605)). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found differences in inheritance pattern and phenotypic variability. Therefore, the following disease entities have been split into two disease entities: autosomal recessive CDAN2 (OMIM: 224100) & autosomal dominant Cowden Syndrome 7 (OMIM: 616858). A separate curation for Cowden Syndrome 7 was deemed not necessary by the Prenatal GCEP. 17 variants (missense, nonsense, splicing, frameshift) that have been reported in well over 20 probands probands in 4 publications (PMIDs: 19561605, 19621418, 27471141, 37373084) are included in this curation. Much more evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The prenatal phenotype includes fetal hydrops and anemia requiring transfusions before birth. The literature suggests that biallelic loss-of-function variants in SEC23B are incompatible with life. Neonatal jaundice and anemia are common in patients. The mechanism of pathogenicity is reported to be loss-of-function. This gene-disease relationship is also supported by experimental evidence (mouse model, expression-level evidence (PMIDs: 19561605, 34954140)). Expression-level data shows that SEC23B is expressed during differentiation of hematopoietic stem cells. The mouse model shows significant reduction in red blood cell count, hemoglobin levels, and hematocrit in the mutant mice compared to the wild-type. In summary, there is definitive evidence supporting the relationship between SEC23B and autosomal recessive CDANII. This been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Prenatal GCEP on the meeting date 10/2/2024 (SOP Version 10).
Inheritance Pattern: AR
Disease ID:MONDO:0009134
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0019403
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0014802
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0009134
Submitter: Laboratory for Molecular Medicine
This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.
Inheritance Pattern: AR
Disease ID:MONDO:0009134
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0009134
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009134
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0014802
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Endocrine; Gastrointestinal; Hematologic; Oncologic
Intervention: Gastrointestinal; Hematologic; Oncologic
Rationale: 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
Comments: Heterozygotes with variants related to Anemia, dyserythropoietic congenital, type II may have mild manifestations
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SEC23B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006363.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 202 | 2 | 208 | ||
| missense | 3 | 26 | 205 | 17 | 251 | |
| nonsense | 18 | 8 | 1 | 27 | ||
| start loss | 1 | 1 | ||||
| frameshift | 18 | 17 | 1 | 36 | ||
| splice donor/acceptor (+/-2bp) | 7 | 18 | 8 | 33 | ||
| Total | 46 | 69 | 220 | 219 | 2 | 556 |
Highest pathogenic variant AF is 0.0002654807
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006354.2 | 19 | MANE Select | |
| Ensembl | ENSP00000497473.1 | 19 | MANE Select | |
| RefSeq | NP_001166216.1 | 19 | Standard | |
| RefSeq | NP_001166217.1 | 19 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sec23b | Danio rerio | Structure: nucleate erythrocyte Quality: immature abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Sterol Regulatory Element-Binding Proteins (SREBP) signalling
Biological Process
- intracellular protein transport
- positive regulation of GTPase activity
- COPII-coated vesicle cargo loading
Molecular Function
- GTPase activator activity
- protein binding
Cellular Component
- Golgi membrane
- endoplasmic reticulum
- endoplasmic reticulum membrane
- cytosol
- endomembrane system
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000336714
- Coding exons
- 19
- Length
- 53923
- Individuals with no LoFs
- 125574
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 174
- Defined
- 125748
- p
- 0.000692
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.473 | 390 | 417 | 0.935 | 0.0000234 | 5029 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00052 | 0.00052 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00054 | 0.00054 | rare |
| Finnish | 0.00042 | 0.00042 | rare |
| European (Non-Finnish) | 0.00095 | 0.00093 | rare |
| South Asian | 0.00072 | 0.00072 | rare |
| Other | 0.00066 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.152
Intolerance Scores
- LoFtool
- 0.120
- RVIS EVS
- 0.49
- RVIS percentile EVS
- 79.61
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.738
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |