GeneBe

SEC24D

protein-coding

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

Gene summary

The protein encoded by this gene is a member of the SEC24 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec24p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. This gene product is implicated in the shaping of the vesicle, and also in cargo selection and concentration. Mutations in this gene have been associated with Cole-Carpenter syndrome, a disorder affecting bone formation, resulting in craniofacial malformations and bones that break easily. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

MANE transcript

NM_014822.4

Inheritance

AR, AD

ClinVar variants

P:45U:238B:152

Top phenotype

Cole-Carpenter syndrome 2

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr4:118,722,823-118,838,683

External References & Databases

Ensembl (ENSG00000150961)NCBI Gene (9871)OMIM (607186)HGNC:10706GenCCUniProt (O94855)AlphaFoldClinVar (SEC24D)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~115.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Cole-Carpenter syndrome 2MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014573

Submitter: Genomics England PanelApp

Cole-Carpenter syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014573

Submitter: G2P

Cole-Carpenter syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016085

Submitter: Orphanet

osteogenesis imperfecta type 1SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008146

Submitter: Orphanet

epilepsyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005027

Submitter: Ambry Genetics

Cole-Carpenter syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014573

Submitter: Labcorp Genetics (formerly Invitae)

Cole-Carpenter syndrome 2MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014573

Submitter: Ambry Genetics

Cole-Carpenter syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014573

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Cole-Carpenter syndrome 2AR

Manifestation: Craniofacial; Dental; Musculoskeletal

Intervention: General

Rationale: 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

Refs: 25683121; 26467156; 27942778; 30462379Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEC24D variants in ClinVar

7 Conditions Cataloged
not providedTotal: 451
Inborn genetic diseasesTotal: 135
not specifiedTotal: 46
Cole-Carpenter syndrome 2Total: 42
SEC24D-related disorderTotal: 29
SeizureTotal: 1
Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014822.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
123
clinvar
3
clinvar
 128
missense
5
clinvar
3
clinvar
229
clinvar
22
clinvar
4
clinvar
 263
nonsense
9
clinvar
5
clinvar
 14
start loss
1
clinvar
 1
frameshift
9
clinvar
5
clinvar
1
clinvar
 15
splice donor/acceptor (+/-2bp)
1
clinvar
6
clinvar
7
clinvar
 14
Total24212381457435

Highest pathogenic variant AF is 0.000039251456

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_014822.4RefSeqNP_055637.222MANE Select
ENST00000280551.11EnsemblENSP00000280551.622MANE Select
NM_001318066.2RefSeqNP_001304995.122Standard
ENST00000419654.6EnsemblENSP00000388324.210Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
sec24dDanio rerio

Structure: chondrocyte

Quality: undifferentiated

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
  • Vesicle-mediated transport
  • Membrane Trafficking
  • Post-translational protein modification

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

Molecular Function

  • SNARE binding
  • protein binding
  • zinc ion binding

Cellular Component

  • Golgi membrane
  • endoplasmic reticulum membrane
  • cytosol
  • ER to Golgi transport vesicle membrane
  • COPII vesicle coat

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000280551
Coding exons
22
Length
115861
Individuals with no LoFs
125673
Homozygous LoFs
0
Heterozygous LoFs
75
Defined
125748
p
0.000298
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.434655600.8300.00002796744
Missense (PolyPhen)149216.160.68932606
Synonymous0.6641902020.9410.00001082018
Loss of Function3.972151.80.4050.00000269614

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.00110.0010notable
Ashkenazi Jewish0.000210.00020rare
East Asian0.000580.00054rare
Finnish00.0absent
European (Non-Finnish)0.000220.00021rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.124

Intolerance Scores

LoFtool
0.443
RVIS EVS
1.18
RVIS percentile EVS
92.84

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.757

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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