Cole-Carpenter syndrome 2

Summary

Cole-Carpenter syndrome 2 (MONDO:0014573) is a disease caused by SEC24D (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SEC24D (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 46

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Cole-Carpenter syndrome 2
Mondo ID	MONDO:0014573
OMIM	616294
UMLS	C4225382
MedGen	905199
GARD	0016077
Is cancer (heuristic)	no

Also known as: CLCRP2 · Cole-Carpenter syndrome 2 · Cole-Carpenter syndrome caused by mutation in SEC24D · Cole-Carpenter syndrome type 2 · SEC24D Cole-Carpenter syndrome

Data availability: 46 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Cole-Carpenter syndrome › Cole-Carpenter syndrome 2

Related subtypes (1): Cole-Carpenter syndrome 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

46 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 10 pathogenic, 8 likely pathogenic, 7 benign/likely benign, 6 benign, 2 conflicting classifications of pathogenicity, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
189339	NM_014822.4(SEC24D):c.3044C>T (p.Ser1015Phe)	SEC24D	Pathogenic	criteria provided, multiple submitters, no conflicts
189340	NM_014822.4(SEC24D):c.613C>T (p.Gln205Ter)	SEC24D	Pathogenic	no assertion criteria provided
189341	NM_014822.4(SEC24D):c.2933A>C (p.Gln978Pro)	SEC24D	Pathogenic	no assertion criteria provided
2072182	NM_014822.4(SEC24D):c.267del (p.Val90fs)	SEC24D	Pathogenic	criteria provided, multiple submitters, no conflicts
4279086	NM_014822.4(SEC24D):c.2496+1811T>G	SEC24D	Pathogenic	criteria provided, single submitter
638178	NM_014822.4(SEC24D):c.113dup (p.Thr39fs)	SEC24D	Pathogenic	criteria provided, single submitter
638179	NM_014822.4(SEC24D):c.2496G>T (p.Gln832His)	SEC24D	Pathogenic	no assertion criteria provided
638180	NM_014822.4(SEC24D):c.2723G>A (p.Cys908Tyr)	SEC24D	Pathogenic	no assertion criteria provided
638183	NM_014822.4(SEC24D):c.875C>T (p.Pro292Leu)	SEC24D	Pathogenic	no assertion criteria provided
638184	NM_014822.4(SEC24D):c.1450C>T (p.Arg484Ter)	SEC24D	Pathogenic	no assertion criteria provided
2664317	NM_014822.4(SEC24D):c.1055T>A (p.Leu352Ter)	SEC24D	Likely pathogenic	criteria provided, single submitter
2664324	NM_014822.4(SEC24D):c.1724G>C (p.Gly575Ala)	SEC24D	Likely pathogenic	criteria provided, single submitter
3242255	NM_014822.4(SEC24D):c.958C>T (p.Pro320Ser)	SEC24D	Likely pathogenic	no assertion criteria provided
4077493	NM_014822.4(SEC24D):c.40C>T (p.Gln14Ter)	SEC24D	Likely pathogenic	criteria provided, single submitter
4292519	NM_014822.4(SEC24D):c.8_23dup (p.Pro10fs)	SEC24D	Likely pathogenic	criteria provided, single submitter
4813292	NM_014822.4(SEC24D):c.2361C>T (p.Asn787=)	SEC24D	Likely pathogenic	criteria provided, single submitter
4813750	NM_014822.4(SEC24D):c.2T>C (p.Met1Thr)	SEC24D	Likely pathogenic	criteria provided, single submitter
4819376	NM_014822.4(SEC24D):c.2168_2169delinsAA (p.Cys723Ter)	SEC24D	Likely pathogenic	criteria provided, single submitter
1080663	NM_014822.4(SEC24D):c.2681C>T (p.Thr894Met)	SEC24D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
733430	NM_014822.4(SEC24D):c.2135A>C (p.Asn712Thr)	SEC24D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3363159	NM_014822.4(SEC24D):c.-167C>T	LOC121725182	Uncertain significance	criteria provided, single submitter
1032642	NM_014822.4(SEC24D):c.1614-10T>A	SEC24D	Uncertain significance	criteria provided, single submitter
1205869	NM_014822.4(SEC24D):c.2734C>T (p.Arg912Cys)	SEC24D	Uncertain significance	criteria provided, multiple submitters, no conflicts
1315221	NM_014822.4(SEC24D):c.1790A>T (p.Asp597Val)	SEC24D	Uncertain significance	criteria provided, multiple submitters, no conflicts
183297	NM_014822.4(SEC24D):c.697G>C (p.Gly233Arg)	SEC24D	Uncertain significance	criteria provided, single submitter
2066124	NM_014822.4(SEC24D):c.781C>T (p.Pro261Ser)	SEC24D	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435798	NM_014822.4(SEC24D):c.1261T>C (p.Ser421Pro)	SEC24D	Uncertain significance	criteria provided, single submitter
2435799	NM_014822.4(SEC24D):c.719G>A (p.Gly240Glu)	SEC24D	Uncertain significance	criteria provided, single submitter
4161785	NM_014822.4(SEC24D):c.722G>T (p.Gly241Val)	SEC24D	Uncertain significance	criteria provided, multiple submitters, no conflicts
638181	NM_014822.4(SEC24D):c.2842T>C (p.Ser948Pro)	SEC24D	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SEC24D	Strong	Autosomal recessive	Cole-Carpenter syndrome 2	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SEC24D	Orphanet:2050	Cole-Carpenter syndrome
SEC24D	Orphanet:216796	Osteogenesis imperfecta type 1

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SEC24D	HGNC:10706	ENSG00000150961	O94855	Protein transport protein Sec24D	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SEC24D	Protein transport protein Sec24D	Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SEC24D	Transcription factor	no		Znf_Sec23_Sec24, Sec23/24_trunk_dom, Sec23/24_helical_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
islet of Langerhans	1
jejunal mucosa	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SEC24D	263	ubiquitous	marker	stromal cell of endometrium, jejunal mucosa, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SEC24D	1,176

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SEC24D	O94855	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	1	393.8×	0.026	SEC24D
Cargo concentration in the ER	1	335.9×	0.026	SEC24D
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	317.2×	0.026	SEC24D
COPII-mediated vesicle transport	1	163.1×	0.028	SEC24D
Metabolism of steroids	1	137.6×	0.028	SEC24D
ER to Golgi Anterograde Transport	1	132.8×	0.028	SEC24D
SARS-CoV-2-host interactions	1	119.0×	0.028	SEC24D
Transport to the Golgi and subsequent modification	1	102.9×	0.028	SEC24D
MHC class II antigen presentation	1	89.2×	0.028	SEC24D
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.028	SEC24D
SARS-CoV-2 Infection	1	80.4×	0.028	SEC24D
Class I MHC mediated antigen processing & presentation	1	70.1×	0.030	SEC24D
Asparagine N-linked glycosylation	1	60.1×	0.032	SEC24D
SARS-CoV Infections	1	55.4×	0.032	SEC24D
Membrane Trafficking	1	37.1×	0.044	SEC24D
Vesicle-mediated transport	1	34.8×	0.044	SEC24D
Metabolism of lipids	1	31.6×	0.044	SEC24D
Viral Infection Pathways	1	30.8×	0.044	SEC24D
Adaptive Immune System	1	29.8×	0.044	SEC24D
Infectious disease	1	24.8×	0.050	SEC24D
Post-translational protein modification	1	19.2×	0.062	SEC24D
Disease	1	13.1×	0.084	SEC24D
Immune System	1	13.0×	0.084	SEC24D
Metabolism of proteins	1	12.4×	0.084	SEC24D
Metabolism	1	11.6×	0.086	SEC24D

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
COPII-coated vesicle cargo loading	1	991.3×	0.004	SEC24D
endoplasmic reticulum to Golgi vesicle-mediated transport	1	135.9×	0.015	SEC24D
in utero embryonic development	1	72.0×	0.015	SEC24D
intracellular protein transport	1	64.8×	0.015	SEC24D

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SEC24D	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SEC24D

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SEC24D	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.