Bent bone dysplasia syndrome 2

Summary

Bent bone dysplasia syndrome 2 (MONDO:0859573) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	bent bone dysplasia syndrome 2
Mondo ID	MONDO:0859573
OMIM	620076
DOID	DOID:0060993
UMLS	C5774233
MedGen	1824006
GARD	0026746
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › bent bone dysplasia › familial bent bone dysplasia syndrome › bent bone dysplasia syndrome 2

Related subtypes (1): bent bone dysplasia 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

4 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4849351	NM_005560.6(LAMA5):c.1336C>T (p.Arg446Ter)	LAMA5	Likely pathogenic	criteria provided, single submitter
1710302	NM_005560.6(LAMA5):c.6157C>T (p.Arg2053Cys)	LAMA5	Uncertain significance	criteria provided, single submitter
3251980	NM_005560.6(LAMA5):c.10703C>A (p.Pro3568His)	LAMA5	Uncertain significance	criteria provided, single submitter
1184836	NM_005560.6(LAMA5):c.4213G>A (p.Ala1405Thr)	LAMA5	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LAMA5	Orphanet:521450	LAMA5-related multisystemic syndrome
LAMA5	Orphanet:656	Hereditary steroid-resistant nephrotic 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
LAMA5	HGNC:6485	ENSG00000130702	O15230	Laminin subunit alpha-5	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LAMA5	Laminin subunit alpha-5	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LAMA5	Other/Unknown	no		Laminin_IV, EGF, TNFR/NGFR_Cys_rich_reg

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
metanephros cortex	1
right hemisphere of cerebellum	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LAMA5	264	ubiquitous	marker	right uterine tube, right hemisphere of cerebellum, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LAMA5	2,519

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LAMA5	O15230	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. 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
MET promotes cell motility	1	601.0×	0.009	LAMA5
Attachment of bacteria to epithelial cells	1	496.5×	0.009	LAMA5
Laminin interactions	1	380.7×	0.009	LAMA5
MET activates PTK2 signaling	1	380.7×	0.009	LAMA5
Signaling by MET	1	317.2×	0.009	LAMA5
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.009	LAMA5
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.011	LAMA5
Non-integrin membrane-ECM interactions	1	154.3×	0.013	LAMA5
ECM proteoglycans	1	150.3×	0.013	LAMA5
Degradation of the extracellular matrix	1	117.7×	0.014	LAMA5
Interleukin-4 and Interleukin-13 signaling	1	102.9×	0.015	LAMA5
Signaling by Interleukins	1	64.2×	0.021	LAMA5
Extracellular matrix organization	1	63.1×	0.021	LAMA5
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.023	LAMA5
Cytokine Signaling in Immune system	1	40.8×	0.028	LAMA5
Immune System	1	13.0×	0.082	LAMA5
Signal Transduction	1	10.2×	0.098	LAMA5

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
trunk neural crest cell migration	1	8426.0×	0.002	LAMA5
morphogenesis of a polarized epithelium	1	4213.0×	0.002	LAMA5
postsynapse organization	1	2407.4×	0.003	LAMA5
morphogenesis of embryonic epithelium	1	1532.0×	0.003	LAMA5
branching involved in salivary gland morphogenesis	1	1404.3×	0.003	LAMA5
regulation of epithelial cell proliferation	1	936.2×	0.004	LAMA5
skeletal system morphogenesis	1	495.6×	0.005	LAMA5
hair follicle development	1	383.0×	0.005	LAMA5
branching involved in ureteric bud morphogenesis	1	366.4×	0.005	LAMA5
substrate adhesion-dependent cell spreading	1	343.9×	0.005	LAMA5
regulation of embryonic development	1	330.4×	0.005	LAMA5
regulation of cell adhesion	1	306.4×	0.005	LAMA5
odontogenesis of dentin-containing tooth	1	300.9×	0.005	LAMA5
lung development	1	198.3×	0.008	LAMA5
muscle organ development	1	166.8×	0.008	LAMA5
integrin-mediated signaling pathway	1	160.5×	0.008	LAMA5
regulation of cell migration	1	157.5×	0.008	LAMA5
protein localization to plasma membrane	1	108.7×	0.011	LAMA5
cilium assembly	1	73.6×	0.015	LAMA5
cell migration	1	61.5×	0.017	LAMA5
cell adhesion	1	37.5×	0.027	LAMA5

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
LAMA5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
E	Difficult family or no structure, no drug	1	LAMA5

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)
LAMA5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.