Smith-McCort dysplasia

Summary

Smith-McCort dysplasia (MONDO:0015799) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		16	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Smith-McCort dysplasia
Mondo ID	MONDO:0015799
MeSH	C564589
OMIM	607326
Orphanet	178355
DOID	DOID:0060247
ICD-11	1800275830
SNOMED CT	715862006
UMLS	C1846431
MedGen	375887
GARD	0010620
Is cancer (heuristic)	no

Also known as: Smith McCort dysplasia · Smith-McCort dwarfism

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › spondyloepiphyseal dysplasia › Smith-McCort dysplasia

Related subtypes (43): hip dysplasia, Beukes type, spondyloepiphyseal dysplasia with congenital joint dislocations, Marshall syndrome, metatropic dysplasia, spondyloepiphyseal dysplasia with punctate corneal dystrophy, spondyloepiphyseal dysplasia, MacDermot type, progressive pseudorheumatoid arthropathy of childhood, otospondylomegaepiphyseal dysplasia, Dyggve-Melchior-Clausen disease, dyssegmental dysplasia, Rolland-Desbuquois type, Silverman-Handmaker type dyssegmental dysplasia, Wolcott-Rallison syndrome, Schimke immuno-osseous dysplasia, Richieri Costa-da Silva syndrome, Schwartz-Jampel syndrome, X-linked spondyloepimetaphyseal dysplasia, CODAS syndrome, spondyloepiphyseal dysplasia, Reardon type, brachyolmia-amelogenesis imperfecta syndrome, spondyloepiphyseal dysplasia with coronal craniosynostosis, cataracts, cleft palate, and intellectual disability, anauxetic dysplasia, spondyloepiphyseal dysplasia, Kimberley type, spondyloepiphyseal dysplasia, Cantu type, Ehlers-Danlos syndrome, spondylocheirodysplastic type, spondylo-megaepiphyseal-metaphyseal dysplasia, brachydactylous dwarfism, Mseleni type, TMEM165-congenital disorder of glycosylation, Steel syndrome, cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome, Roifman syndrome, progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome, even-plus syndrome, cono-spondylar dysplasia, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, Stickler syndrome, spondyloepiphyseal dysplasia tarda, spondyloepiphyseal dysplasia, kondo-fu type, spondyloepiphyseal dysplasia, nishimura type, immunoskeletal dysplasia with neurodevelopmental abnormalities, COL2A1-related spondyloepiphyseal dysplasia, MIR140-related spondyloepiphyseal dysplasia, MGP-related spondyloepiphyseal dysplasia, spondyloepiphyseal dysplasia, Holling type

Subtypes (2): Smith-McCort dysplasia 1, Smith-McCort dysplasia 2

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 3 · 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
DYM	Strong	Autosomal recessive	Smith-McCort dysplasia 1	8
RAB33B	Strong	Autosomal recessive	Smith-McCort dysplasia 2	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAB33B	Orphanet:178355	Smith-McCort dysplasia
DYM	Orphanet:178355	Smith-McCort dysplasia
DYM	Orphanet:239	Dyggve-Melchior-Clausen disease

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
RAB33B	HGNC:16075	ENSG00000172007	Q9H082	Ras-related protein Rab-33B	gencc
DYM	HGNC:21317	ENSG00000141627	Q7RTS9	Dymeclin	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAB33B	Ras-related protein Rab-33B	The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.
DYM	Dymeclin	Necessary for correct organization of Golgi apparatus.

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)
RAB33B	Other/Unknown	no		Small_GTPase, Small_GTP-bd, P-loop_NTPase
DYM	Other/Unknown	no		Dymeclin

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
calcaneal tendon	1
saphenous vein	1
vein	1
bone marrow cell	1
embryo	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAB33B	282	ubiquitous	marker	calcaneal tendon, saphenous vein, vein
DYM	254	ubiquitous	marker	bone marrow cell, embryo, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAB33B	1,936
DYM	1,298

Intra-cohort edges

A	B	Sources
DYM	RAB33B	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RAB33B	Q9H082	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DYM	Q7RTS9	87.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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
Intra-Golgi traffic	1	259.6×	0.006	RAB33B
TBC/RABGAPs	1	259.6×	0.006	RAB33B
RAB geranylgeranylation	1	173.0×	0.006	RAB33B

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
negative regulation of constitutive secretory pathway	1	8426.0×	0.002	RAB33B
regulation of retrograde vesicle-mediated transport, Golgi to ER	1	4213.0×	0.002	RAB33B
regulation of Golgi organization	1	561.7×	0.005	RAB33B
Rab protein signal transduction	1	495.6×	0.005	RAB33B
protein localization to phagophore assembly site	1	495.6×	0.005	RAB33B
protein localization to Golgi apparatus	1	401.2×	0.005	RAB33B
regulation of exocytosis	1	351.1×	0.005	RAB33B
intra-Golgi vesicle-mediated transport	1	263.3×	0.006	RAB33B
skeletal system morphogenesis	1	247.8×	0.006	RAB33B
bone development	1	138.1×	0.009	DYM
autophagosome assembly	1	112.3×	0.010	RAB33B
Golgi organization	1	66.9×	0.016	DYM
protein transport	1	21.9×	0.045	RAB33B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
RAB33B	0	0
DYM	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	2	RAB33B, DYM

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RAB33B	0	—
DYM	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.