SEC24D

SEC24 homolog D, COPII coat complex component, the group of COPII coat complex

Basic information

Region (hg38): 4:118722823-118838683

Links

ENSG00000150961 ∙ NCBI:9871 ∙ OMIM:607186 ∙ HGNC:10706 ∙ Uniprot:O94855 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Cole-Carpenter syndrome 2 (Moderate), mode of inheritance: AR
• Cole-Carpenter syndrome (Supportive), mode of inheritance: AD
• osteogenesis imperfecta type 1 (Supportive), mode of inheritance: AD
• Cole-Carpenter syndrome 2 (Moderate), mode of inheritance: AR
• epilepsy (Limited), mode of inheritance: AR
• Cole-Carpenter syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cole-Carpenter syndrome 2	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; Dental; Musculoskeletal	25683121; 26467156; 27942778; 30462379

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEC24D gene.

• not provided (11 variants)
• Cole-Carpenter syndrome 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEC24D 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				83	6	89
missense	1	1	149	13	4	168
nonsense	4	3				7
start loss						0
frameshift	6	1	1			8
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)		5				5
splice region			7	11	8	26
non coding			4	84	46	134
Total	11	11	158	180	56

Highest pathogenic variant AF is 0.0000197

Variants in SEC24D

This is a list of pathogenic ClinVar variants found in the SEC24D region.

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

Position	Type	Phenotype	Significance	ClinVar
4-118723343-T-C			Likely benign (May 18, 2019)
4-118723512-CAATT-C			Likely benign (Jan 28, 2023)
4-118723540-T-C		Inborn genetic diseases	Uncertain significance (May 15, 2024)
4-118723551-A-C		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
4-118723555-A-T			Uncertain significance (Aug 24, 2023)
4-118723562-C-T			Uncertain significance (Aug 04, 2023)
4-118723566-A-G		SEC24D-related disorder	Likely benign (Mar 20, 2019)
4-118723565-C-CTT			Uncertain significance (Feb 14, 2023)
4-118723567-TAAG-T			Uncertain significance (May 19, 2022)
4-118723570-G-A		Cole-Carpenter syndrome 2	Pathogenic (Oct 23, 2020)
4-118723573-G-A			Uncertain significance (Jul 01, 2022)
4-118723579-C-G			Uncertain significance (Jul 06, 2022)
4-118723580-C-T			Uncertain significance (Aug 19, 2022)
4-118723600-A-C			Uncertain significance (Nov 19, 2023)
4-118723602-C-G			Likely benign (Sep 19, 2022)
4-118723612-C-T			Uncertain significance (Apr 26, 2022)
4-118723621-A-G			Uncertain significance (Jul 28, 2022)
4-118723631-G-A			Pathogenic (Jun 28, 2022)
4-118723636-C-T			Uncertain significance (Feb 05, 2022)
4-118723637-G-A		SEC24D-related disorder	Pathogenic/Likely pathogenic (Sep 22, 2023)
4-118723649-T-C		Inborn genetic diseases	Uncertain significance (Feb 07, 2023)
4-118723657-TA-T			Uncertain significance (Aug 16, 2022)
4-118723660-G-A			Likely benign (Jan 24, 2018)
4-118723660-GA-G			Benign (Sep 17, 2022)
4-118723660-G-GA		Cole-Carpenter syndrome 2	Benign (Jan 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEC24D	protein_coding	protein_coding	ENST00000280551	22	115861

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.33e-7	1.00	125673	0	75	125748	0.000298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.43	465	560	0.830	0.0000279	6744
Missense in Polyphen		149	216.16	0.6893		2606
Synonymous	0.664	190	202	0.941	0.0000108	2018
Loss of Function	3.97	21	51.8	0.405	0.00000269	614

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00119	0.00119
Ashkenazi Jewish	0.000208	0.000198
East Asian	0.000581	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000216	0.000211
Middle Eastern	0.000581	0.000544
South Asian	0.0000330	0.0000327
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 (PubMed:17499046, PubMed:20427317, PubMed:18843296). Plays a central role in cargo selection within the COPII complex and together with SEC24C may have a different specificity compared to SEC24A and SEC24B (PubMed:17499046, PubMed:20427317, PubMed:18843296). May more specifically package GPI-anchored proteins through the cargo receptor TMED10 (PubMed:20427317). May also be specific for IxM motif-containing cargos like the SNAREs GOSR2 and STX5 (PubMed:18843296). {ECO:0000269|PubMed:17499046, ECO:0000269|PubMed:18843296, ECO:0000269|PubMed:20427317}.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);Sterol Regulatory Element-Binding Proteins (SREBP) signalling;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: 0.124

Intolerance Scores

• loftool: 0.443
• rvis_EVS: 1.18
• rvis_percentile_EVS: 92.84

Haploinsufficiency Scores

• pHI: 0.691
• hipred: Y
• hipred_score: 0.593
• ghis: 0.444

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.757

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sec24d
• 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); normal phenotype

Zebrafish Information Network

• Gene name: sec24d
• Affected structure: chondrocyte
• Phenotype tag: abnormal
• Phenotype quality: undifferentiated

Gene ontology

• Biological process: in utero embryonic development;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;COPII vesicle coating;COPII-coated vesicle cargo loading
• Cellular component: Golgi membrane;endoplasmic reticulum membrane;cytosol;ER to Golgi transport vesicle membrane;COPII vesicle coat
• Molecular function: SNARE binding;protein binding;zinc ion binding