RAB23-related Carpenter syndrome

Summary

RAB23-related Carpenter syndrome (MONDO:0008710) is a disease caused by RAB23 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: RAB23 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 105

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	RAB23-related Carpenter syndrome
Mondo ID	MONDO:0008710
OMIM	201000
DOID	DOID:0061098
SNOMED CT	205813009
UMLS	C4551510
MedGen	1644017
GARD	0015128
Is cancer (heuristic)	no

Also known as: ACPS 2 · acrocephalopolysyndactyly type 2 · Carpenter syndrome · Carpenter syndrome 1 · Carpenter syndrome caused by mutation in RAB23 · Carpenter syndrome type 1 · CRPT1 · RAB23 Carpenter syndrome · RAB23-related Carpenter syndrome

Data availability: 105 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic craniosynostosis › acrocephalosyndactyly › acrocephalopolysyndactyly › Carpenter syndrome › RAB23-related Carpenter syndrome

Related subtypes (1): MEGF8-related Carpenter syndrome

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

105 retrieved; paginated sample, class counts are floors:

50 uncertain significance, 13 likely benign, 12 likely pathogenic, 10 conflicting classifications of pathogenicity, 7 benign, 6 pathogenic, 4 pathogenic/likely pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1073623	NM_016277.5(RAB23):c.145C>T (p.Arg49Ter)	RAB23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1210114	NM_016277.5(RAB23):c.398+1G>A	RAB23	Pathogenic	criteria provided, single submitter
18426	NM_016277.5(RAB23):c.86dup (p.Tyr29Ter)	RAB23	Pathogenic	no assertion criteria provided
2740005	NM_016277.5(RAB23):c.238C>T (p.Arg80Ter)	RAB23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280858	NM_016277.5(RAB23):c.82C>T (p.Arg28Ter)	RAB23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3764578	NM_016277.5(RAB23):c.208del (p.Glu70fs)	RAB23	Pathogenic	criteria provided, single submitter
4060661	NM_016277.5(RAB23):c.362_363insG (p.Asn121fs)	RAB23	Pathogenic	criteria provided, single submitter
4591	NM_016277.5(RAB23):c.434T>A (p.Leu145Ter)	RAB23	Pathogenic	criteria provided, multiple submitters, no conflicts
4592	NM_016277.5(RAB23):c.408dup (p.Glu137Ter)	RAB23	Pathogenic	criteria provided, multiple submitters, no conflicts
664887	NM_016277.5(RAB23):c.5del (p.Leu2fs)	RAB23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1210462	NM_016277.5(RAB23):c.559del (p.Ser187fs)	RAB23	Likely pathogenic	criteria provided, single submitter
3594052	NM_016277.5(RAB23):c.399-2A>G	RAB23	Likely pathogenic	criteria provided, single submitter
3594053	NM_016277.5(RAB23):c.394A>T (p.Lys132Ter)	RAB23	Likely pathogenic	criteria provided, single submitter
3594054	NM_016277.5(RAB23):c.315_316del (p.Lys106fs)	RAB23	Likely pathogenic	criteria provided, single submitter
4077457	NM_016277.5(RAB23):c.155+1G>T	RAB23	Likely pathogenic	criteria provided, single submitter
4817031	NM_016277.5(RAB23):c.156-1G>T	RAB23	Likely pathogenic	criteria provided, single submitter
4817032	NM_016277.5(RAB23):c.16dup (p.Met6fs)	RAB23	Likely pathogenic	criteria provided, single submitter
4817033	NM_016277.5(RAB23):c.177_183del (p.Arg59fs)	RAB23	Likely pathogenic	criteria provided, single submitter
4817034	NM_016277.5(RAB23):c.510del (p.Gln171fs)	RAB23	Likely pathogenic	criteria provided, single submitter
4817035	NM_016277.5(RAB23):c.522_525del (p.Lys174fs)	RAB23	Likely pathogenic	criteria provided, single submitter
4817036	NM_016277.5(RAB23):c.575-2A>C	RAB23	Likely pathogenic	criteria provided, single submitter
4817037	NM_016277.5(RAB23):c.606del (p.Gly203fs)	RAB23	Likely pathogenic	criteria provided, single submitter
1055018	NM_016277.5(RAB23):c.712T>G (p.Ter238Glu)	RAB23	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211976	NM_016277.5(RAB23):c.218C>T (p.Ala73Val)	RAB23	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3357168	NM_016277.5(RAB23):c.398+6del	RAB23	Conflicting classifications of pathogenicity	no assertion criteria provided
357639	NM_016277.5(RAB23):c.714A>G (p.Ter238=)	RAB23	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357642	NM_016277.5(RAB23):c.536A>C (p.Glu179Ala)	RAB23	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357643	NM_016277.5(RAB23):c.398+9G>A	RAB23	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
772095	NM_016277.5(RAB23):c.54A>G (p.Gly18=)	RAB23	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
908657	NM_016277.5(RAB23):c.156-9T>C	RAB23	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
RAB23	Definitive	Autosomal recessive	RAB23-related Carpenter syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAB23	Orphanet:65759	Carpenter syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RAB23	HGNC:14263	ENSG00000112210	Q9ULC3	Ras-related protein Rab-23	gencc,clinvar
BAG2	HGNC:938	ENSG00000112208	O95816	BAG family molecular chaperone regulator 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAB23	Ras-related protein Rab-23	The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.
BAG2	BAG family molecular chaperone regulator 2	Co-chaperone for HSP70 and HSC70 chaperone proteins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RAB23	Other/Unknown	no		Small_GTPase, Small_GTP-bd, P-loop_NTPase
BAG2	Other/Unknown	no		BAG_domain, BAG2

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cauda epididymis	2
saphenous vein	1
secondary oocyte	1
biceps brachii	1
heart right ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAB23	264	ubiquitous	marker	cauda epididymis, saphenous vein, secondary oocyte
BAG2	249	ubiquitous	marker	cauda epididymis, heart right ventricle, biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BAG2	3,692
RAB23	1,223

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RAB23	Q9ULC3	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BAG2	O95816	86.55

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cellular response to heat stress	1	196.9×	0.019	BAG2
Dengue Virus Genome Translation and Replication	1	158.6×	0.019	BAG2
RAB geranylgeranylation	1	86.5×	0.021	RAB23
Regulation of HSF1-mediated heat shock response	1	69.6×	0.021	BAG2
Cellular responses to stress	1	18.4×	0.063	BAG2
Cellular responses to stimuli	1	15.7×	0.063	BAG2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein metabolic process	1	2808.7×	0.005	BAG2
craniofacial suture morphogenesis	1	842.6×	0.005	RAB23
positive regulation of protein processing	1	601.9×	0.005	BAG2
GTP metabolic process	1	561.7×	0.005	RAB23
positive regulation of proteasomal protein catabolic process	1	495.6×	0.005	BAG2
negative regulation of protein import into nucleus	1	468.1×	0.005	RAB23
cellular defense response	1	159.0×	0.011	RAB23
negative regulation of protein ubiquitination	1	142.8×	0.011	BAG2
autophagosome assembly	1	112.3×	0.013	RAB23
protein folding	1	51.7×	0.025	BAG2
cilium assembly	1	36.8×	0.031	RAB23
protein stabilization	1	33.4×	0.031	BAG2
intracellular protein transport	1	32.4×	0.031	RAB23

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BAG2	1	2
RAB23	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	BAG2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BAG2	8	Binding:8

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	BAG2

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	1	BAG2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RAB23

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)
RAB23	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.