SEC24D

Chr 4AR

SEC24 homolog D, COPII component

Also known as: CLCRP2

NCBI Gene: 9871ENSG00000150961UniProt: O94855

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]

Primary Disease Associations & Inheritance

Cole-Carpenter syndrome 2MIM #616294
AR
541
ClinVar variants
53
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SEC24D
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 Pathogenic / Likely Pathogenic· 194 VUS of 541 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.58LOEUF
pLI 0.000
Z-score 3.97
OE 0.41 (0.29–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.43Z-score
OE missense 0.83 (0.77–0.90)
465 obs / 560.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.41 (0.29–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.77–0.90)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 21 / 51.8Missense obs/exp: 465 / 560.1Syn Z: 0.66

ClinVar Variant Classifications

541 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic12
VUS194
Likely Benign221
Benign65
Conflicting8
41
Pathogenic
12
Likely Pathogenic
194
VUS
221
Likely Benign
65
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
5
27
0
41
Likely Pathogenic
5
2
5
0
12
VUS
1
176
16
1
194
Likely Benign
1
13
104
103
221
Benign
0
4
54
7
65
Conflicting
—8
Total16200206111541

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SEC24D · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SEC24D-related syndromic osteogenesis imperfecta

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cole-Carpenter syndrome 2

MIM #616294

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.
Alazami AM et al.·Cell Rep
2015
SEC24D depletion induces osteogenic differentiation deficiency by inactivating the ATF6/TGF-β/Runx2 regulatory loop.
Zhang J et al.·Commun Biol
2025
RTP801 interacts with the tRNA ligase complex and dysregulates its RNA ligase activity in Alzheimer's disease.
Campoy-Campos G et al.·Nucleic Acids Res
2024
SEC24C deficiency causes trafficking and glycosylation abnormalities in an epileptic encephalopathy with cataracts and dyserythropoeisis.
Bögershausen N et al.·JCI Insight
2025
Rare variant modifier analysis identifies variants in SEC24D associated with orofacial cleft subtypes.
Curtis SW et al.·Hum Genet
2023
Clinical and Pathologic Description of Three Aneurysmal Bone Cyst Cases With Novel USP6 Fusion Partners Including SEC24D, HNRNPC, and ERRFI1.
Blackburn PR et al.·Genes Chromosomes Cancer
2025Case report
Identifying rare variants in genes related to bone phenotypes in a cohort of postmenopausal women.
Patiño-Salazar JD et al.·Osteoporos Int
2025Cohort
A homozygous pathogenic missense variant broadens the phenotypic and mutational spectrum of CREB3L1-related osteogenesis imperfecta.
Guillemyn B et al.·Hum Mol Genet
2019
Monoallelic and biallelic CREB3L1 variant causes mild and severe osteogenesis imperfecta, respectively.
Keller RB et al.·Genet Med
2018Case report
Phenotypic Expansion: Fetus With Cole-Carpenter Type 2 Presenting With Novel Neonatal Lethal Skeletal Dysplasia.
Burrill N et al.·Am J Med Genet A
2025Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools