hip dysplasia, Beukes type

Summary

hip dysplasia, Beukes type (MONDO:0007726) is a disease with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Cohort genes: 3
• ClinVar variants: 9
• Phenotypes (HPO): 11

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0001385	Hip dysplasia	Very frequent (80-99%)
HP:0002758	Osteoarthritis	Very frequent (80-99%)
HP:0004348	Abnormality of bone mineral density	Very frequent (80-99%)
HP:0005930	Abnormality of epiphysis morphology	Very frequent (80-99%)
HP:0006429	Broad femoral neck	Very frequent (80-99%)
HP:0009107	Abnormal ossification involving the femoral head and neck	Very frequent (80-99%)
HP:0010574	Abnormality of the epiphysis of the femoral head	Very frequent (80-99%)
HP:0011849	Abnormal bone ossification	Very frequent (80-99%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002808	Kyphosis	Occasional (5-29%)
HP:0002812	Coxa vara	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hip dysplasia, Beukes type
Mondo ID	MONDO:0007726
MeSH	C564185
OMIM	142669
Orphanet	2114
DOID	DOID:0111367
SNOMED CT	721148005
UMLS	C1840572
MedGen	333593
GARD	0002690
Is cancer (heuristic)	no

Also known as: Beukes familial hip dysplasia · Beukes hip dysplasia · BFHD · BHD · Cilliers-Beighton syndrome · hip dysplasia Beukes type · hip dysplasia, Beukes type · premature degenerative osteoarthropathy of the hip

Data availability: 9 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 › hip dysplasia, Beukes type

Related subtypes (43): 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, 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

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

9 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
204613	NM_018359.5(UFSP2):c.868T>C (p.Tyr290His)	UFSP2	Pathogenic	no assertion criteria provided
437868	NM_018359.5(UFSP2):c.1277A>C (p.Asp426Ala)	UFSP2	Pathogenic	criteria provided, multiple submitters, no conflicts
932944	NM_018359.5(UFSP2):c.344T>A (p.Val115Glu)	UFSP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3065681	NM_018359.5(UFSP2):c.1333G>A (p.Gly445Arg)	ANKRD37	Uncertain significance	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
4080963	NM_018359.5(UFSP2):c.38T>C (p.Ile13Thr)	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

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
UFSP2	HGNC:25640	ENSG00000109775	Q9NUQ7	Ufm1-specific protease 2	gencc,clinvar
ANKRD37	HGNC:29593	ENSG00000186352	Q7Z713	Ankyrin repeat domain-containing protein 37	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: 1 · 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
Scaffold/PPI	1	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UFSP2	Other/Unknown	no		UFSP1/2_DUB_cat, UFSP2-like_2nd
ANKRD37	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
CFAP96	Other/Unknown	no		CFAP96

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	2
calcaneal tendon	1
hindlimb stylopod muscle	1
triceps brachii	1
lower esophagus mucosa	1
secondary oocyte	1
bronchial epithelial cell	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
ANKRD37	249	ubiquitous	marker	lower esophagus mucosa, oocyte, secondary oocyte
CFAP96	187	broad	marker	oocyte, right uterine tube, bronchial epithelial cell

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANKRD37	1,048
UFSP2	1,045
CFAP96	378

Intra-cohort edges

A	B	Sources
ANKRD37	CFAP96	string_interaction
CFAP96	UFSP2	string_interaction

Structural data

PDB: 0 · AlphaFold-only: 3 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
UFSP2	Q9NUQ7	91.21
CFAP96	A7E2U8	74.34
ANKRD37	Q7Z713	71.93

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 3 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: 3

Druggability breadth: 0 of 3 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
ANKRD37	0	0
CFAP96	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	UFSP2, ANKRD37, CFAP96

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
UFSP2	0	—
ANKRD37	0	—
CFAP96	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.