Bruck syndrome 2

Summary

Bruck syndrome 2 (MONDO:0012217) is a disease caused by PLOD2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: PLOD2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 108

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bruck syndrome 2
Mondo ID	MONDO:0012217
MeSH	C537407
OMIM	609220
UMLS	C1836602
MedGen	373129
GARD	0010023
Is cancer (heuristic)	no

Also known as: BRKS2 · Bruck syndrome 2 · Bruck syndrome caused by mutation in PLOD2 · Bruck syndrome type 2 · PLOD2 Bruck syndrome

Data availability: 108 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Bruck syndrome › Bruck syndrome 2

Related subtypes (1): Bruck syndrome 1

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

108 retrieved; paginated sample, class counts are floors:

53 uncertain significance, 12 benign, 11 conflicting classifications of pathogenicity, 11 likely pathogenic, 10 benign/likely benign, 6 pathogenic, 4 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323472	NM_182943.3(PLOD2):c.67del (p.Cys23fs)	PLOD2	Pathogenic	criteria provided, single submitter
1324939	NM_182943.3(PLOD2):c.1483C>T (p.Arg495Ter)	PLOD2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458515	NM_182943.3(PLOD2):c.8dup (p.Cys4fs)	PLOD2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1696826	NM_182943.3(PLOD2):c.648C>A (p.Cys216Ter)	PLOD2	Pathogenic	criteria provided, single submitter
2574996	NM_182943.3(PLOD2):c.1318C>T (p.Arg440Ter)	PLOD2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374012	NM_182943.3(PLOD2):c.2038C>T (p.Arg680Ter)	PLOD2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
41424	NM_182943.3(PLOD2):c.1559dup (p.Val523fs)	PLOD2	Pathogenic	criteria provided, multiple submitters, no conflicts
4292588	NM_182943.3(PLOD2):c.1501-2A>G	PLOD2	Pathogenic	criteria provided, single submitter
7641	NM_182943.3(PLOD2):c.1886C>T (p.Thr629Ile)	PLOD2	Pathogenic	no assertion criteria provided
7642	NM_182943.3(PLOD2):c.1865G>T (p.Gly622Val)	PLOD2	Pathogenic	no assertion criteria provided
2581069	NM_182943.3(PLOD2):c.1872T>G (p.Tyr624Ter)	PLOD2	Likely pathogenic	criteria provided, single submitter
3065125	NM_182943.3(PLOD2):c.1848+1G>T	PLOD2	Likely pathogenic	criteria provided, single submitter
3363157	NM_182943.3(PLOD2):c.1754A>T (p.Asp585Val)	PLOD2	Likely pathogenic	criteria provided, single submitter
3588642	NM_182943.3(PLOD2):c.1359-1G>A	PLOD2	Likely pathogenic	criteria provided, single submitter
3588643	NM_182943.3(PLOD2):c.502G>T (p.Gly168Ter)	PLOD2	Likely pathogenic	criteria provided, single submitter
3588644	NM_182943.3(PLOD2):c.202-2A>G	PLOD2	Likely pathogenic	criteria provided, single submitter
3775580	NM_182943.3(PLOD2):c.900dup (p.Gly301fs)	PLOD2	Likely pathogenic	criteria provided, single submitter
4278143	NM_182943.3(PLOD2):c.1599dup (p.Gly534fs)	PLOD2	Likely pathogenic	criteria provided, single submitter
4846892	NM_182943.3(PLOD2):c.1682G>A (p.Trp561Ter)	PLOD2	Likely pathogenic	criteria provided, single submitter
7643	NM_182943.3(PLOD2):c.1856G>A (p.Arg619His)	PLOD2	Likely pathogenic	criteria provided, single submitter
930725	NM_182943.3(PLOD2):c.351dup (p.Phe118fs)	PLOD2	Likely pathogenic	criteria provided, single submitter
343650	NM_182943.3(PLOD2):c.471G>A (p.Val157=)	LOC129389144	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1444936	NM_182943.3(PLOD2):c.1045A>G (p.Lys349Glu)	PLOD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1705607	NM_182943.3(PLOD2):c.1958C>G (p.Pro653Arg)	PLOD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
343644	NM_182943.3(PLOD2):c.2121+14T>C	PLOD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
343645	NM_182943.3(PLOD2):c.1732A>G (p.Ile578Val)	PLOD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
343648	NM_182943.3(PLOD2):c.616-13T>A	PLOD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
374011	NM_182943.3(PLOD2):c.1361G>T (p.Gly454Val)	PLOD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
753441	NM_182943.3(PLOD2):c.1451G>A (p.Arg484His)	PLOD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
807467	NM_182943.3(PLOD2):c.1280A>G (p.Asn427Ser)	PLOD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
PLOD2	Definitive	Autosomal recessive	Bruck syndrome 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLOD2	Orphanet:2771	Bruck syndrome

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
PLOD2	HGNC:9082	ENSG00000152952	O00469	Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLOD2	Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2	Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLOD2	Enzyme (other)	yes	1.14.11.4	Procol_lys_dOase, Oxoglu/Fe-dep_dioxygenase_dom, Pro_4_hyd_alph

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
calcaneal tendon	1
jejunal mucosa	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLOD2	288	ubiquitous	marker	tibia, calcaneal tendon, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLOD2	1,703

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLOD2	O00469	92.63

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Collagen biosynthesis and modifying enzymes	1	170.4×	0.006	PLOD2

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 hydroxylysine biosynthetic process	1	5617.3×	7e-04	PLOD2
collagen biosynthetic process	1	1053.2×	0.002	PLOD2
collagen fibril organization	1	224.7×	0.006	PLOD2
response to hypoxia	1	95.8×	0.010	PLOD2

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
PLOD2	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
PLOD2	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PLOD2	1.14.11.4, 2.4.1.50	procollagen-lysine 5-dioxygenase, procollagen galactosyltransferase

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	1	PLOD2
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)
PLOD2	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.