SEC23A

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

Basic information

Region (hg38): 14:39031918-39109646

Links

ENSG00000100934 ∙ NCBI:10484 ∙ OMIM:610511 ∙ HGNC:10701 ∙ Uniprot:Q15436 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• craniolenticulosutural dysplasia (Limited), mode of inheritance: AR
• craniolenticulosutural dysplasia (Supportive), mode of inheritance: AR
• craniolenticulosutural dysplasia (Limited), mode of inheritance: AR
• craniolenticulosutural dysplasia (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Craniolenticulosutural dysplasia	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Ophthalmologic	12677423; 16980979; 21039434; 34580982

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEC23A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEC23A 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				23	3	26
missense		1	61	1	1	64
nonsense			3			3
start loss						0
frameshift			3			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			1	5	2	8
non coding				15	52	67
Total	0	2	68	39	56

Variants in SEC23A

This is a list of pathogenic ClinVar variants found in the SEC23A region.

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

Position	Type	Phenotype	Significance	ClinVar
14-39033275-AT-A		Craniolenticulosutural dysplasia	Uncertain significance (Nov 07, 2022)
14-39033335-G-GA		Craniolenticulosutural dysplasia	Benign (Jan 31, 2024)
14-39033422-A-AAATAGAAC			Benign (Jul 27, 2018)
14-39033426-G-GAA			Benign (May 23, 2021)
14-39033427-C-CAATAA			Benign (May 23, 2021)
14-39038863-G-T			Benign (Sep 05, 2018)
14-39039011-G-A		Craniolenticulosutural dysplasia	Likely benign (Feb 24, 2022)
14-39039025-A-T		Craniolenticulosutural dysplasia	Uncertain significance (Jan 23, 2023)
14-39039048-T-C		not specified	Uncertain significance (Dec 08, 2023)
14-39039073-G-A		Craniolenticulosutural dysplasia • SEC23A-related disorder	Likely benign (Sep 01, 2022)
14-39039085-G-A		Craniolenticulosutural dysplasia	Likely benign (Feb 03, 2022)
14-39039093-G-A			Uncertain significance (Apr 22, 2021)
14-39039403-C-T			Benign (Jul 27, 2018)
14-39040727-C-CTT		Craniolenticulosutural dysplasia	Likely benign (Aug 04, 2023)
14-39040770-T-C		Craniolenticulosutural dysplasia	Uncertain significance (Jul 26, 2023)
14-39040813-G-T		SEC23A-related disorder	Likely benign (Sep 28, 2020)
14-39040823-A-C			Uncertain significance (Oct 22, 2019)
14-39040830-G-A		not specified	Uncertain significance (Mar 29, 2023)
14-39040836-T-C		Craniolenticulosutural dysplasia • not specified	Uncertain significance (Dec 05, 2022)
14-39040902-A-G		Craniolenticulosutural dysplasia	Likely benign (Jun 20, 2023)
14-39040969-T-C			Benign (Jul 27, 2018)
14-39042748-CT-C			Benign (Sep 05, 2018)
14-39042866-G-A		Craniolenticulosutural dysplasia • not specified	Conflicting classifications of pathogenicity (Feb 09, 2023)
14-39042878-G-A		Craniolenticulosutural dysplasia	Likely benign (Sep 28, 2023)
14-39042882-A-G		Craniolenticulosutural dysplasia	Benign (Jan 18, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEC23A	protein_coding	protein_coding	ENST00000307712	19	77728

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.07e-11	0.999	125692	0	56	125748	0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.78	319	422	0.756	0.0000216	5009
Missense in Polyphen		77	124.95	0.61626		1500
Synonymous	0.507	123	130	0.944	0.00000602	1476
Loss of Function	3.01	26	48.7	0.534	0.00000270	527

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000437	0.000437
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000599	0.000598
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000599	0.000598
South Asian	0.000229	0.000229
Other	0.00	0.00

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:0000269|PubMed:16980979, ECO:0000269|PubMed:17499046, ECO:0000269|PubMed:18843296, ECO:0000269|PubMed:27551091, ECO:0000269|PubMed:8898360}.
• Disease: DISEASE: Craniolenticulosutural dysplasia (CLSD) [MIM:607812]: Autosomal recessive syndrome characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms and skeletal defects. {ECO:0000269|PubMed:16980979}. 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;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;MHC class II antigen presentation;Immune System;Adaptive Immune System;Class I MHC mediated antigen processing & presentation;Cargo concentration in the ER;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport;Antigen Presentation: Folding, assembly and peptide loading of class I MHC (Consensus)

Recessive Scores

• pRec: 0.168

Intolerance Scores

• loftool: 0.500
• rvis_EVS: -0.78
• rvis_percentile_EVS: 12.88

Haploinsufficiency Scores

• pHI: 0.689
• hipred: Y
• hipred_score: 0.589
• ghis: 0.657

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sec23a
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: sec23a
• Affected structure: pharyngeal arch cartilage
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: antigen processing and presentation of peptide antigen via MHC class I;intracellular protein transport;endoplasmic reticulum to Golgi vesicle-mediated transport;antigen processing and presentation of exogenous peptide antigen via MHC class II;positive regulation of GTPase activity;COPII vesicle coating;protein localization to plasma membrane;COPII-coated vesicle cargo loading
• Cellular component: endoplasmic reticulum membrane;cytosol;ER to Golgi transport vesicle membrane;extrinsic component of membrane;COPII vesicle coat;endoplasmic reticulum exit site
• Molecular function: GTPase activator activity;protein binding;zinc ion binding