Spondyloepiphyseal dysplasia, kondo-fu type

Summary

Spondyloepiphyseal dysplasia, kondo-fu type (MONDO:0032721) is a disease caused by MBTPS1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MBTPS1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spondyloepiphyseal dysplasia, kondo-fu type
Mondo ID	MONDO:0032721
OMIM	618392
DOID	DOID:0112283
UMLS	C5193071
MedGen	1683128
GARD	0025729
NORD	2027
Is cancer (heuristic)	no

Also known as: SEDKF

Data availability: 16 ClinVar variants · 4 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 › spondyloepiphyseal dysplasia, kondo-fu type

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, Smith-McCort dysplasia, cono-spondylar dysplasia, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, Stickler syndrome, spondyloepiphyseal dysplasia tarda, 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

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

16 retrieved; paginated sample, class counts are floors:

7 pathogenic, 4 likely pathogenic, 3 uncertain significance, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1334154	NM_003791.4(MBTPS1):c.3157T>C (p.Ter1053Arg)	MBTPS1	Pathogenic	no assertion criteria provided
1334417	NM_003791.4(MBTPS1):c.1064T>G (p.Val355Gly)	MBTPS1	Pathogenic	no assertion criteria provided
3906948	D365*	MBTPS1	Pathogenic	no assertion criteria provided
625457	NM_003791.4(MBTPS1):c.285dup (p.Asp96Ter)	MBTPS1	Pathogenic	no assertion criteria provided
625458	NM_003791.4(MBTPS1):c.1094A>G (p.Asp365Gly)	MBTPS1	Pathogenic	no assertion criteria provided
812671	NM_003791.4(MBTPS1):c.2948G>A (p.Trp983Ter)	MBTPS1	Pathogenic	criteria provided, multiple submitters, no conflicts
976662	NM_003791.4(MBTPS1):c.1995C>G (p.Tyr665Ter)	MBTPS1	Pathogenic	criteria provided, single submitter
976663	NM_003791.4(MBTPS1):c.955G>T (p.Val319Phe)	LOC126862423	Likely pathogenic	criteria provided, single submitter
2582787	NM_003791.4(MBTPS1):c.2255G>T (p.Gly752Val)	MBTPS1	Likely pathogenic	no assertion criteria provided
3065874	NM_003791.4(MBTPS1):c.2896C>T (p.Arg966Ter)	MBTPS1	Likely pathogenic	criteria provided, single submitter
4849444	NM_003791.4(MBTPS1):c.2781T>A (p.Cys927Ter)	MBTPS1	Likely pathogenic	criteria provided, single submitter
1469225	NM_003791.4(MBTPS1):c.371A>G (p.Lys124Arg)	MBTPS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2582788	NM_003791.4(MBTPS1):c.2831+5G>T	MBTPS1	Uncertain significance	criteria provided, single submitter
3067824	NM_003791.4(MBTPS1):c.2927C>T (p.Ser976Phe)	MBTPS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1598351	NM_003791.4(MBTPS1):c.17T>C (p.Ile6Thr)	MBTPS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1632561	NM_003791.4(MBTPS1):c.738G>A (p.Gly246=)	MBTPS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
MBTPS1	Strong	Autosomal recessive	spondyloepiphyseal dysplasia, kondo-fu type	4

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
MBTPS1	HGNC:15456	ENSG00000140943	Q14703	Membrane-bound transcription factor site-1 protease	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MBTPS1	Membrane-bound transcription factor site-1 protease	Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and FAM20C.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MBTPS1	Protease	yes	3.4.21.112	Peptidase_S8/S53_dom, Peptidase_S8_subtilisin-rel, Peptidase_S8_His-AS

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
endometrium epithelium	1
pituitary gland	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MBTPS1	286	ubiquitous	marker	stromal cell of endometrium, endometrium epithelium, pituitary gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MBTPS1	2,242

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MBTPS1	Q14703	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
ATF6B (ATF6-beta) activates chaperones	1	2855.0×	0.005	MBTPS1
ATF6 (ATF6-alpha) activates chaperones	1	1903.3×	0.005	MBTPS1
CREB3 factors activate genes	1	1268.9×	0.005	MBTPS1
Assembly of active LPL and LIPC lipase complexes	1	601.0×	0.007	MBTPS1
Plasma lipoprotein remodeling	1	475.8×	0.008	MBTPS1
Unfolded Protein Response (UPR)	1	356.9×	0.008	MBTPS1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	317.2×	0.008	MBTPS1
Plasma lipoprotein assembly, remodeling, and clearance	1	228.4×	0.010	MBTPS1
Metabolism of steroids	1	137.6×	0.015	MBTPS1
Post-translational protein phosphorylation	1	100.2×	0.018	MBTPS1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.019	MBTPS1
Cellular responses to stress	1	36.8×	0.041	MBTPS1
Metabolism of lipids	1	31.6×	0.041	MBTPS1
Cellular responses to stimuli	1	31.5×	0.041	MBTPS1
Transport of small molecules	1	25.1×	0.048	MBTPS1
Post-translational protein modification	1	19.2×	0.059	MBTPS1
Metabolism of proteins	1	12.4×	0.086	MBTPS1
Metabolism	1	11.6×	0.086	MBTPS1

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
ATF6-mediated unfolded protein response	1	2106.5×	0.003	MBTPS1
regulation of cholesterol biosynthetic process	1	1532.0×	0.003	MBTPS1
membrane protein intracellular domain proteolysis	1	1203.7×	0.003	MBTPS1
regulation of vesicle-mediated transport	1	1123.5×	0.003	MBTPS1
mitotic G2 DNA damage checkpoint signaling	1	443.5×	0.006	MBTPS1
lysosome organization	1	306.4×	0.006	MBTPS1
endoplasmic reticulum unfolded protein response	1	295.6×	0.006	MBTPS1
cholesterol metabolic process	1	195.9×	0.007	MBTPS1
protein processing	1	170.2×	0.007	MBTPS1
response to endoplasmic reticulum stress	1	166.8×	0.007	MBTPS1
protein maturation	1	163.6×	0.007	MBTPS1
protein import into nucleus	1	144.0×	0.008	MBTPS1
proteolysis	1	34.2×	0.029	MBTPS1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MBTPS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MBTPS1	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MBTPS1	3.4.21.112	site-1 protease

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	1	MBTPS1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
MBTPS1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.