SEC24D

Chr 4AR

SEC24 homolog D, COPII component

Also known as: CLCRP2

NCBI Gene: 9871 ENSG00000150961 UniProt: O94855 OMIM: 607186

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cole-Carpenter syndrome 2MIM #616294

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Cole-Carpenter syndrome 2; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.58

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in SEC24D?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 41

1,216 rare PASS variants

Rare truncating (LoF)

1 in 640

166 rare PASS variants

Rare synonymous (reference)

1 in 92

441 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SEC24D. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 67	1 in 870
South Asian	~43k	1 in 39	1 in 390
Remaining (unassigned)	~30k	1 in 37	1 in 800
European (Finnish)	~27k	1 in 180	≈ 1 in 6,400
Admixed American	~22k	1 in 45	1 in 260
African / African American	~21k	1 in 48	1 in 530
East Asian	~20k	1 in 56	1 in 220
Ashkenazi Jewish	~13k	1 in 130	1 in 990
Middle Eastern	~2,884	1 in 34	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 17 of 22 coding exons well covered in gnomAD exomes; exons 7, 10, 14, 16, 22 marginal. Genomes: all 22.? see exons ↓