brachydactyly type B2

Summary

brachydactyly type B2 (MONDO:0012658) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 7
• Phenotypes (HPO): 9

Clinical features

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0001773	Short foot	Very frequent (80-99%)
HP:0001817	Absent fingernail	Very frequent (80-99%)
HP:0001831	Short toe	Very frequent (80-99%)
HP:0001857	Short distal phalanx of toe	Very frequent (80-99%)
HP:0005831	Type B brachydactyly	Very frequent (80-99%)
HP:0009882	Short distal phalanx of finger	Very frequent (80-99%)
HP:0005048	Synostosis of carpal bones	Frequent (30-79%)
HP:0006101	Finger syndactyly	Frequent (30-79%)
HP:0009773	Symphalangism affecting the phalanges of the hand	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	brachydactyly type B2
Mondo ID	MONDO:0012658
OMIM	611377
Orphanet	140908
DOID	DOID:0110975
ICD-11	891810441
SNOMED CT	770406002
UMLS	C1969652
MedGen	409880
GARD	0016963
Is cancer (heuristic)	no

Also known as: BDB2 · brachydactyly, type B2

Data availability: 7 ClinVar variants · 1 GenCC gene-disease record.

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 B2

Related subtypes (1): brachydactyly type B1

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

7 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1299560	NM_005450.6(NOG):c.379G>T (p.Glu127Ter)	NOG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6702	NM_005450.6(NOG):c.499C>G (p.Arg167Gly)	NOG	Pathogenic	no assertion criteria provided
6703	NM_005450.6(NOG):c.103C>T (p.Pro35Ser)	NOG	Pathogenic	criteria provided, single submitter
6708	NM_005450.6(NOG):c.103C>G (p.Pro35Ala)	NOG	Pathogenic	no assertion criteria provided
3382219	NM_005450.6(NOG):c.509del (p.Pro170fs)	NOG	Likely pathogenic	criteria provided, single submitter
375295	NM_005450.6(NOG):c.611G>A (p.Arg204Gln)	NOG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3382452	NM_005450.6(NOG):c.545G>C (p.Arg182Pro)	NOG	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 5 · 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
NOG	Supportive	Autosomal dominant	brachydactyly type B2	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NOG	Orphanet:140908	Brachydactyly type B2
NOG	Orphanet:140917	Stapes ankylosis with broad thumbs and toes
NOG	Orphanet:1412	Tarsal-carpal coalition syndrome
NOG	Orphanet:3237	Multiple synostoses syndrome
NOG	Orphanet:3250	Proximal symphalangism

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
NOG	HGNC:7866	ENSG00000183691	Q13253	Noggin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NOG	Noggin	Inhibitor of bone morphogenetic proteins (BMP) signaling which is required for growth and patterning of the neural tube and somite.

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)
NOG	Other/Unknown	no		Noggin, Cystine-knot_cytokine

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
buccal mucosa cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
pigmented layer of retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NOG	155	broad	marker	pigmented layer of retina, buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NOG	2,338

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NOG	Q13253	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Formation of paraxial mesoderm	1	407.9×	0.003	NOG
Signaling by BMP	1	356.9×	0.003	NOG

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
negative regulation of cardiac epithelial to mesenchymal transition	1	16852.0×	0.002	NOG
positive regulation of glomerulus development	1	8426.0×	0.002	NOG
neural plate morphogenesis	1	5617.3×	0.002	NOG
cell differentiation in hindbrain	1	5617.3×	0.002	NOG
neural plate anterior/posterior regionalization	1	5617.3×	0.002	NOG
short-term synaptic potentiation	1	5617.3×	0.002	NOG
prostatic bud formation	1	4213.0×	0.002	NOG
axial mesoderm development	1	3370.4×	0.002	NOG
notochord morphogenesis	1	3370.4×	0.002	NOG
ventricular compact myocardium morphogenesis	1	2407.4×	0.002	NOG
regulation of fibroblast growth factor receptor signaling pathway	1	2407.4×	0.002	NOG
atrial cardiac muscle tissue morphogenesis	1	2407.4×	0.002	NOG
ureteric bud formation	1	2407.4×	0.002	NOG
negative regulation of cartilage development	1	2106.5×	0.002	NOG
negative regulation of cardiac muscle cell proliferation	1	1872.4×	0.002	NOG
heart trabecula morphogenesis	1	1872.4×	0.002	NOG
membranous septum morphogenesis	1	1685.2×	0.002	NOG
pharyngeal arch artery morphogenesis	1	1685.2×	0.002	NOG
negative regulation of astrocyte differentiation	1	1532.0×	0.002	NOG
embryonic skeletal joint morphogenesis	1	1532.0×	0.002	NOG
endoderm formation	1	1404.3×	0.002	NOG
endocardial cushion formation	1	1404.3×	0.002	NOG
nodal signaling pathway	1	1123.5×	0.003	NOG
somite development	1	1123.5×	0.003	NOG
lung morphogenesis	1	1053.2×	0.003	NOG
cranial skeletal system development	1	936.2×	0.003	NOG
positive regulation of branching involved in ureteric bud morphogenesis	1	802.5×	0.003	NOG
motor neuron axon guidance	1	702.2×	0.003	NOG
middle ear morphogenesis	1	702.2×	0.003	NOG
regulation of neuronal synaptic plasticity	1	674.1×	0.003	NOG

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 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
NOG	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	NOG

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)
NOG	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.