brachydactyly type B1

Summary

brachydactyly type B1 (MONDO:0007220) is a disease caused by ROR2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ROR2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 344

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	brachydactyly type B1
Mondo ID	MONDO:0007220
MeSH	C566196
OMIM	113000
Orphanet	572385
DOID	DOID:0110969
UMLS	C1862112
MedGen	349432
GARD	0018009
Is cancer (heuristic)	no

Also known as: BDB1 · brachydactyly type B caused by mutation in ROR2 · brachydactyly, type B1 · ROR2 brachydactyly type B

Data availability: 344 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › brachydactyly › brachydactyly type B › brachydactyly type B1

Related subtypes (1): brachydactyly type B2

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

344 retrieved; paginated sample, class counts are floors:

195 uncertain significance, 67 conflicting classifications of pathogenicity, 20 likely benign, 20 benign/likely benign, 19 benign, 11 pathogenic, 10 likely pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
268044	46;XX;ins(2;9)(q24.3;p22.1p24.3)dn		Pathogenic	criteria provided, single submitter
1455301	NM_004560.4(ROR2):c.1582C>T (p.Arg528Ter)	ROR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3381923	NM_004560.4(ROR2):c.1205dup (p.Met402fs)	ROR2	Pathogenic	criteria provided, single submitter
4293893	NM_004560.4(ROR2):c.1398dup (p.Glu467fs)	ROR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7304	NM_004560.4(ROR2):c.2265C>A (p.Tyr755Ter)	ROR2	Pathogenic	criteria provided, single submitter
7305	NM_004560.4(ROR2):c.2246G>A (p.Trp749Ter)	ROR2	Pathogenic	no assertion criteria provided
7306	NM_004560.4(ROR2):c.2249del (p.Gly750fs)	ROR2	Pathogenic	no assertion criteria provided
7311	NM_004560.4(ROR2):c.1321_1325del (p.Arg441fs)	ROR2	Pathogenic	no assertion criteria provided
7312	NM_004560.4(ROR2):c.2247G>A (p.Trp749Ter)	ROR2	Pathogenic	no assertion criteria provided
7316	NM_004560.4(ROR2):c.1366dup (p.Leu456fs)	ROR2	Pathogenic	criteria provided, single submitter
7317	NM_004560.4(ROR2):c.2244del (p.Trp749fs)	ROR2	Pathogenic	no assertion criteria provided
7318	NM_004560.4(ROR2):c.1324C>T (p.Arg442Ter)	ROR2	Pathogenic	criteria provided, multiple submitters, no conflicts
983455	NM_004560.4(ROR2):c.1189C>T (p.Arg397Ter)	ROR2	Pathogenic	criteria provided, multiple submitters, no conflicts
1066325	NM_004560.4(ROR2):c.175+1G>A	ROR2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3597717	NM_004560.4(ROR2):c.2353del (p.Arg785fs)	ROR2	Likely pathogenic	criteria provided, single submitter
3597728	NM_004560.4(ROR2):c.2018C>G (p.Ser673Ter)	ROR2	Likely pathogenic	criteria provided, single submitter
3597736	NM_004560.4(ROR2):c.1855del (p.Arg619fs)	ROR2	Likely pathogenic	criteria provided, single submitter
3597756	NM_004560.4(ROR2):c.1137del (p.Gln380fs)	ROR2	Likely pathogenic	criteria provided, single submitter
3597761	NM_004560.4(ROR2):c.1083dup (p.His362fs)	ROR2	Likely pathogenic	criteria provided, single submitter
3597771	NM_004560.4(ROR2):c.799G>T (p.Glu267Ter)	ROR2	Likely pathogenic	criteria provided, single submitter
4532131	NM_004560.4(ROR2):c.2265delinsTT (p.Tyr755_Asn756insTer)	ROR2	Likely pathogenic	criteria provided, single submitter
7308	NM_004560.4(ROR2):c.550C>T (p.Arg184Cys)	ROR2	Likely pathogenic	criteria provided, single submitter
983464	NM_004560.4(ROR2):c.1096C>T (p.Arg366Trp)	ROR2	Likely pathogenic	criteria provided, single submitter
1006928	NM_004560.4(ROR2):c.1746G>A (p.Thr582=)	ROR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030817	NM_004560.4(ROR2):c.2305C>T (p.Gln769Ter)	ROR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1148887	NM_004560.4(ROR2):c.2698G>A (p.Ala900Thr)	ROR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1187123	NM_004560.4(ROR2):c.1969C>T (p.Arg657Cys)	ROR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1418155	NM_004560.4(ROR2):c.768C>T (p.Cys256=)	ROR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1429220	NM_004560.4(ROR2):c.1606G>A (p.Val536Ile)	ROR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1529738	NM_004560.4(ROR2):c.1480G>A (p.Gly494Ser)	ROR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
ROR2	Definitive	Autosomal dominant	brachydactyly type B1	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ROR2	Orphanet:1507	Autosomal recessive Robinow syndrome
ROR2	Orphanet:572385	Brachydactyly type B1

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
ROR2	HGNC:10257	ENSG00000169071	Q01974	Tyrosine-protein kinase transmembrane receptor ROR2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ROR2	Tyrosine-protein kinase transmembrane receptor ROR2	Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ROR2	Kinase	yes	2.7.10.1	Kringle, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom

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
body of uterus	1
mucosa of stomach	1
muscle layer of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ROR2	188	ubiquitous	marker	muscle layer of sigmoid colon, mucosa of stomach, body of uterus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ROR2	1,813

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ROR2	Q01974	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
WNT5A-dependent internalization of FZD2, FZD5 and ROR2	1	878.5×	0.006	ROR2
PCP/CE pathway	1	300.5×	0.006	ROR2
Beta-catenin independent WNT signaling	1	292.8×	0.006	ROR2
Signaling by WNT	1	112.0×	0.011	ROR2
Signal Transduction	1	10.2×	0.098	ROR2

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
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.020	ROR2
Wnt signaling pathway	1	99.7×	0.020	ROR2
positive regulation of cell migration	1	61.7×	0.022	ROR2
signal transduction	1	16.1×	0.062	ROR2

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
ROR2	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
ROR2	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ROR2	2.7.10.1	receptor protein-tyrosine kinase

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	ROR2
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)
ROR2	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.