Smith-McCort dysplasia 1

Summary

Smith-McCort dysplasia 1 (MONDO:0011814) is a disease caused by DYM (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: DYM (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Smith-McCort dysplasia 1
Mondo ID	MONDO:0011814
OMIM	607326
DOID	DOID:0081270
UMLS	C3888088
MedGen	854757
GARD	0015411
Is cancer (heuristic)	no

Also known as: DYM Smith-McCort dysplasia · SMC · Smc1 · Smith-McCort dysplasia · Smith-McCort dysplasia 1 · Smith-McCort dysplasia caused by mutation in DYM · Smith-McCort dysplasia type 1

Data availability: 12 ClinVar variants · 3 GenCC gene-disease records.

Disease family

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 › Smith-McCort dysplasia 1

Related subtypes (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

ClinVar germline variants

12 retrieved; paginated sample, class counts are floors:

4 conflicting classifications of pathogenicity, 3 pathogenic, 2 pathogenic/likely pathogenic, 1 benign, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
198883	NM_001353214.3(DYM):c.621-2A>G	DYM	Pathogenic	criteria provided, single submitter
3186	NM_001353214.3(DYM):c.396T>A (p.Tyr132Ter)	DYM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3189	NM_001353214.3(DYM):c.259G>A (p.Glu87Lys)	DYM	Pathogenic	criteria provided, single submitter
3191	NM_001353214.3(DYM):c.2043del (p.Lys681fs)	DYM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3193	NM_001353214.3(DYM):c.1789T>C (p.Cys597Arg)	DYM	Pathogenic	no assertion criteria provided
4812814	NM_001353214.3(DYM):c.107T>G (p.Leu36Arg)	DYM	Likely pathogenic	criteria provided, single submitter
287525	NM_001353214.3(DYM):c.620+4T>G	DYM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290755	NM_001353214.3(DYM):c.288-10G>A	DYM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
326895	NM_001353214.3(DYM):c.1251+12T>C	DYM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
726259	NM_017653.6(DYM):c.1461-8T>G	DYM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3583367	NM_001353214.3(DYM):c.1751AAG[1] (p.Glu585del)	DYM	Uncertain significance	criteria provided, single submitter
326907	NM_001353214.3(DYM):c.193+9G>A	DYM	Benign	criteria provided, multiple submitters, no conflicts

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
DYM	Strong	Autosomal recessive	Smith-McCort dysplasia 1	8

Orphanet rare-disease linkage (cohort genes)

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

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
DYM	HGNC:21317	ENSG00000141627	Q7RTS9	Dymeclin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DYM	Dymeclin	Necessary for correct organization of Golgi apparatus.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DYM	Other/Unknown	no		Dymeclin

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
bone marrow cell	1
embryo	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DYM	254	ubiquitous	marker	bone marrow cell, embryo, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DYM	1,298

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DYM	Q7RTS9	87.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
bone development	1	276.3×	0.007	DYM
Golgi organization	1	133.8×	0.007	DYM

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
DYM	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	DYM

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)
DYM	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05650502	Not specified	COMPLETED	Impact of Seasonal Malaria Chemoprevention on Immunity Against Malaria Among Children in Northern Benin