spondyloepiphyseal dysplasia tarda, X-linked

Summary

spondyloepiphyseal dysplasia tarda, X-linked (MONDO:0010737) is a disease caused by TRAPPC2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: TRAPPC2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spondyloepiphyseal dysplasia tarda, X-linked
Mondo ID	MONDO:0010737
OMIM	313400
DOID	DOID:0080362
ICD-11	219612045
UMLS	C3541456
MedGen	762085
GARD	0004985
Is cancer (heuristic)	no

Also known as: SED · SEDT · spondyloepiphyseal dysplasia tarda X-linked · spondyloepiphyseal dysplasia tarda, X-linked · spondyloepiphyseal dysplasia tarda, X-linked recessive · X linked spondyloepiphyseal dysplasia tarda · X-linked spondyloepiphyseal dysplasia

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

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › X-linked disease › spondyloepiphyseal dysplasia tarda, X-linked

Related subtypes (49): X-linked Opitz G/BBB syndrome, X-linked immunoneurologic disorder, X-linked adrenal hypoplasia congenita, X-linked lissencephaly with abnormal genitalia, X-linked severe congenital neutropenia, X-linked distal spinal muscular atrophy type 3, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders, Aland island eye disease, X-linked erythropoietic protoporphyria, X-linked central congenital hypothyroidism with late-onset testicular enlargement, X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome, X-linked acrogigantism due to Xq26 microduplication, Wiskott-Aldrich syndrome, X-linked Alport syndrome, X-linked mandibulofacial dysostosis, X-linked chondrodysplasia punctata, choroideremia, cone dystrophy, X-linked, with tapetal-like sheen, diabetes insipidus, nephrogenic, X-linked, Dyggve-Melchior-Clausen syndrome, X-linked, dyskeratosis congenita, X-linked, X-linked hypohidrotic ectodermal dysplasia, X-linked Ehlers-Danlos syndrome, epidermodysplasia verruciformis, X-linked, exudative vitreoretinopathy 2, X-linked, Aarskog-Scott syndrome, X-linked, hemophilia A, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius, hyper-IgM syndrome type 1, X-linked lymphoproliferative syndrome, macular dystrophy, X-linked, X-linked Emery-Dreifuss muscular dystrophy, X-linked myotubular myopathy, X-linked lethal multiple pterygium syndrome, X-linked retinoschisis, X-linked cerebellar ataxia, adrenoleukodystrophy, Charcot-Marie-Tooth disease type X, X-linked dominant disease, X-linked recessive disease, X-linked hypophosphatemic rickets, X-linked sideroblastic anemia 1, X-linked deafness, X-linked cone-rod dystrophy, X-linked congenital stationary night blindness, X-linked congenital hemolytic anemia, X-linked complex neurodevelopmental disorder, X-linked intellectual disability, leukemia, acute, X-linked

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:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
11512	NM_001011658.4(TRAPPC2):c.93+5G>A	OFD1	Pathogenic	criteria provided, multiple submitters, no conflicts
1802535	NM_001011658.4(TRAPPC2):c.137_138del (p.Leu46fs)	OFD1	Pathogenic	criteria provided, single submitter
2575107	NM_001011658.4(TRAPPC2):c.91A>T (p.Lys31Ter)	OFD1	Pathogenic	no assertion criteria provided
2577913	NM_001011658.4(TRAPPC2):c.225del (p.Phe75fs)	OFD1	Pathogenic	criteria provided, single submitter
3899362	NM_001011658.4(TRAPPC2):c.18del (p.Phe7fs)	OFD1	Pathogenic	criteria provided, single submitter
3382952	NM_001011658.4(TRAPPC2):c.144dup (p.Val49fs)	OFD1	Likely pathogenic	criteria provided, single submitter
4795848	NM_001011658.4(TRAPPC2):c.239-20_239-12delinsAATGAA	OFD1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1332782	NM_001011658.4(TRAPPC2):c.239-10_239-7del	OFD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1706552	NM_001011658.4(TRAPPC2):c.-19G>T	OFD1	Uncertain significance	criteria provided, single submitter
3382470	NM_001011658.4(TRAPPC2):c.-19-2_-19delinsGGA	OFD1	Uncertain significance	criteria provided, single submitter
2437253	NM_001011658.4(TRAPPC2):c.351del (p.Asn118fs)	TRAPPC2	Uncertain significance	criteria provided, single submitter
2428760	NM_001011658.4(TRAPPC2):c.308A>G (p.Tyr103Cys)	OFD1	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 6 · 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
TRAPPC2	Definitive	X-linked	spondyloepiphyseal dysplasia tarda, X-linked	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRAPPC2	Orphanet:93284	Spondyloepiphyseal dysplasia tarda
OFD1	Orphanet:244	Primary ciliary dyskinesia
OFD1	Orphanet:2750	Orofaciodigital syndrome type 1
OFD1	Orphanet:2754	Orofaciodigital syndrome type 6
OFD1	Orphanet:475	Isolated Joubert syndrome
OFD1	Orphanet:791	Retinitis pigmentosa

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
TRAPPC2	HGNC:23068	ENSG00000196459	P0DI81	Trafficking protein particle complex subunit 2	gencc,clinvar
OFD1	HGNC:2567	ENSG00000046651	O75665	Centriole and centriolar satellite protein OFD1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRAPPC2	Trafficking protein particle complex subunit 2	Prevents transcriptional repression and induction of cell death by ENO1.
OFD1	Centriole and centriolar satellite protein OFD1	Component of the centrioles controlling mother and daughter centrioles length.

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)
TRAPPC2	Other/Unknown	no		Sedlin, Longin-like_dom_sf
OFD1	Other/Unknown	no		LisH, OFD1

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
cerebellar cortex	1
cerebellar vermis	1
cortical plate	1
bronchial epithelial cell	1
cervix squamous epithelium	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRAPPC2	279	ubiquitous	marker	cortical plate, cerebellar vermis, cerebellar cortex
OFD1	288	ubiquitous	marker	sperm, bronchial epithelial cell, cervix squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OFD1	2,878
TRAPPC2	1,220

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TRAPPC2	P0DI81	92.44
OFD1	O75665	68.41

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Hedgehog ‘off’ state	1	89.2×	0.018	OFD1
COPII-mediated vesicle transport	1	81.6×	0.018	TRAPPC2
Loss of Nlp from mitotic centrosomes	1	79.3×	0.018	OFD1
Loss of proteins required for interphase microtubule organization from the centrosome	1	79.3×	0.018	OFD1
AURKA Activation by TPX2	1	76.1×	0.018	OFD1
Recruitment of mitotic centrosome proteins and complexes	1	68.0×	0.018	OFD1
Regulation of PLK1 Activity at G2/M Transition	1	63.4×	0.018	OFD1
RAB GEFs exchange GTP for GDP on RABs	1	62.1×	0.018	TRAPPC2
Recruitment of NuMA to mitotic centrosomes	1	58.3×	0.018	OFD1
Anchoring of the basal body to the plasma membrane	1	56.5×	0.018	OFD1

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
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation	1	4213.0×	0.002	OFD1
embryonic body morphogenesis	1	1053.2×	0.004	OFD1
vesicle coat assembly	1	766.0×	0.004	TRAPPC2
epithelial cilium movement involved in determination of left/right asymmetry	1	648.1×	0.004	OFD1
obsolete vesicle tethering	1	495.6×	0.004	TRAPPC2
COPII vesicle coat assembly	1	351.1×	0.005	TRAPPC2
axoneme assembly	1	271.8×	0.005	OFD1
endoplasmic reticulum to Golgi vesicle-mediated transport	1	68.0×	0.018	TRAPPC2
skeletal system development	1	62.9×	0.018	TRAPPC2
cilium assembly	1	36.8×	0.027	OFD1

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
TRAPPC2	0	0
OFD1	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	TRAPPC2, OFD1

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)
TRAPPC2	0	—
OFD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.