SEC24D

Chr 4

SEC24 homolog D, COPII component

Also known as: CLCRP2

NCBI Gene: 9871 ENSG00000150961 UniProt: O94855

SEC24D encodes a component of the COPII coat protein complex that promotes vesicle formation from the endoplasmic reticulum and plays a central role in selecting cargo molecules for transport to the Golgi complex. Mutations cause Cole-Carpenter syndrome, an autosomal recessive disorder characterized by craniofacial malformations and bone fragility. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.584), consistent with its role in fundamental cellular transport processes.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.58

Clinical Summary— SEC24D

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

42 unique Pathogenic / Likely Pathogenic· 242 VUS of 623 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.43Z-score

OE missense 0.83 (0.77–0.90)

465 obs / 560.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.29–0.58)

0≤0.351.4

Missense OE?0.83 (0.77–0.90)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 21 / 51.8Missense obs/exp: 465 / 560.1Syn Z: 0.66

ClinVar Variant Classifications

623 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26

Likely Pathogenic16

VUS242

Likely Benign246

Benign67

Conflicting8

Pathogenic

Likely Pathogenic

242

VUS

246

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	20	5	1	0	26
Likely Pathogenic	11	4	0	1	16
VUS	1	230	10	1	242
Likely Benign	1	13	116	116	246
Benign	0	4	56	7	67
Conflicting	—				8
Total	33	256	183	125	605

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap SEC24D — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →