Spondyloepimetaphyseal dysplasia, di rocco type

Summary

Spondyloepimetaphyseal dysplasia, di rocco type (MONDO:0060702) is a disease caused by UFSP2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: UFSP2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spondyloepimetaphyseal dysplasia, di rocco type
Mondo ID	MONDO:0060702
OMIM	617974
UMLS	C4693799
MedGen	1646454
GARD	0026004
Is cancer (heuristic)	no

Also known as: SEMDDR

Data availability: 8 ClinVar variants · 1 GenCC gene-disease record.

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 › spondyloepimetaphyseal dysplasia › spondyloepimetaphyseal dysplasia, di rocco type

Related subtypes (22): spondyloepimetaphyseal dysplasia-hypotrichosis syndrome, spondyloepimetaphyseal dysplasia, Maroteaux type, spondyloepimetaphyseal dysplasia, Strudwick type, spondyloepimetaphyseal dysplasia, sponastrime type, spondyloepimetaphyseal dysplasia, Irapa type, spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome, spondyloepimetaphyseal dysplasia, Bieganski type, spondyloepimetaphyseal dysplasia-abnormal dentition syndrome, spondyloepimetaphyseal dysplasia, Missouri type, spondyloepimetaphyseal dysplasia, Shohat type, spondyloepimetaphyseal dysplasia, matrilin-3 type, spondyloepimetaphyseal dysplasia, Genevieve type, spondyloepimetaphyseal dysplasia, aggrecan type, spondyloepimetaphyseal dysplasia, Handigodu type, spondyloepimetaphyseal dysplasia, Isidor type, spondyloepimetaphyseal dysplasia, PAPSS2 type, spondyloepimetaphyseal dysplasia with joint laxity, spondyloepimetaphyseal dysplasia, Krakow type, spondyloepimetaphyseal dysplasia, Isidor-Toutain type, COL2A1-related spondyloepiphyseal dysplasia, spondyloepimetaphyseal dysplasia, Guo-Campeau type, spondyloepimetaphyseal dysplasia, Li-Shao-Li 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

8 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 benign, 2 likely pathogenic, 1 uncertain significance, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1098423	NM_018359.5(UFSP2):c.905G>C (p.Cys302Ser)	UFSP2	Pathogenic	no assertion criteria provided
437868	NM_018359.5(UFSP2):c.1277A>C (p.Asp426Ala)	UFSP2	Pathogenic	criteria provided, multiple submitters, no conflicts
4526333	NM_018359.5(UFSP2):c.1277A>G (p.Asp426Gly)	UFSP2	Likely pathogenic	criteria provided, single submitter
916581	NM_018359.5(UFSP2):c.1283A>G (p.His428Arg)	UFSP2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3892811	NM_018359.5(UFSP2):c.253C>G (p.Leu85Val)	CFAP96	Uncertain significance	criteria provided, multiple submitters, no conflicts
1684235	NM_018359.5(UFSP2):c.333+11T>C	CFAP96	Benign	criteria provided, multiple submitters, no conflicts
1684236	NM_018359.5(UFSP2):c.-33C>T	CFAP96	Benign	criteria provided, multiple submitters, no conflicts
780512	NM_018359.5(UFSP2):c.932G>C (p.Cys311Ser)	UFSP2	Benign/Likely 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
UFSP2	Strong	Autosomal dominant	spondyloepimetaphyseal dysplasia, di rocco type	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UFSP2	Orphanet:2114	Hip dysplasia, Beukes type
UFSP2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

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
UFSP2	HGNC:25640	ENSG00000109775	Q9NUQ7	Ufm1-specific protease 2	gencc,clinvar
CFAP96	HGNC:34346	ENSG00000205129	A7E2U8	Cilia-and flagella-associated protein 96	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UFSP2	Ufm1-specific protease 2	Thiol-dependent isopeptidase that specifically cleaves UFM1, a ubiquitin-like modifier protein, from conjugated proteins, such as CD274/PD-L1, CYB5R3, DDRGK1, MRE11, RPL26/uL24, TRIP4 and RPL26/uL24.

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)
UFSP2	Other/Unknown	no		UFSP1/2_DUB_cat, UFSP2-like_2nd
CFAP96	Other/Unknown	no		CFAP96

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
hindlimb stylopod muscle	1
triceps brachii	1
bronchial epithelial cell	1
oocyte	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UFSP2	290	ubiquitous	marker	calcaneal tendon, hindlimb stylopod muscle, triceps brachii
CFAP96	187	broad	marker	oocyte, right uterine tube, bronchial epithelial cell

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UFSP2	1,045
CFAP96	378

Intra-cohort edges

A	B	Sources
CFAP96	UFSP2	string_interaction

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
UFSP2	Q9NUQ7	91.21
CFAP96	A7E2U8	74.34

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
obsolete negative regulation of proteolysis involved in protein catabolic process	1	4213.0×	0.001	UFSP2
regulation of type II interferon production	1	2106.5×	0.001	UFSP2
regulation of intracellular estrogen receptor signaling pathway	1	1872.4×	0.001	UFSP2
ribosome disassembly	1	991.3×	0.002	UFSP2
rescue of stalled cytosolic ribosome	1	481.5×	0.002	UFSP2
proteolysis	1	34.2×	0.029	UFSP2

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
UFSP2	0	0
CFAP96	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	UFSP2, CFAP96

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)
UFSP2	0	—
CFAP96	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.