brachydactyly type A1A

Summary

brachydactyly type A1A (MONDO:0020701) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	brachydactyly type A1A
Mondo ID	MONDO:0020701
GARD	0025215
Is cancer (heuristic)	no

Also known as: BDA1

Data availability: 6 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › brachydactyly › brachydactyly type A1A

Related subtypes (21): Cooks syndrome, brachydactyly-arterial hypertension syndrome, Ballard syndrome, brachydactyly type A1, brachydactyly type A2, brachydactyly type A3, brachydactyly type A4, Osebold-Remondini syndrome, brachydactyly type C, brachydactyly type D, camptobrachydactyly, brachydactyly type A1B, brachydactyly type A1C, brachydactyly type A1D, non-syndromic brachydactyly, brachydactyly type B, brachydactyly type E, brachydactyly type A5, brachydactyly type A7, Berk-Tabatznik syndrome, preaxial digit brachydactyly-webbed fingers

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

6 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1803981	NM_002181.4(IHH):c.415dup (p.His139fs)	IHH	Pathogenic	criteria provided, single submitter
8869	NM_002181.4(IHH):c.298G>A (p.Asp100Asn)	IHH	Pathogenic	criteria provided, multiple submitters, no conflicts
2584388	NM_002181.4(IHH):c.1A>G (p.Met1Val)	IHH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2505482	NM_002181.4(IHH):c.787C>T (p.Gln263Ter)	IHH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683476	NM_002181.4(IHH):c.851C>T (p.Thr284Met)	IHH	Uncertain significance	criteria provided, multiple submitters, no conflicts
334437	NM_002181.4(IHH):c.819C>T (p.Pro273=)	IHH	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
IHH	Orphanet:63446	Acrocapitofemoral dysplasia
IHH	Orphanet:93388	Brachydactyly type A1

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
IHH	HGNC:5956	ENSG00000163501	Q14623	Indian hedgehog protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IHH	Indian hedgehog protein	Plays a role in embryonic morphogenesis; it is involved in the regulation of endochondral skeleton formation, and the development of retinal pigment epithelium (RPE), photoreceptors and periocular tissues.

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)
IHH	Other/Unknown	no		Hedgehog_signalling_dom, Hedgehog, Hedgehog_Hint

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
male germ line stem cell (sensu Vertebrata) in testis	1
mucosa of transverse colon	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IHH	94	broad	marker	mucosa of transverse colon, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IHH	2,370

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IHH	Q14623	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
HHAT G278V doesn’t palmitoylate Hh-Np	1	2284.0×	0.001	IHH
RUNX2 regulates chondrocyte maturation	1	2284.0×	0.001	IHH
Formation of lateral plate mesoderm	1	2284.0×	0.001	IHH
Release of Hh-Np from the secreting cell	1	1427.5×	0.001	IHH
Ligand-receptor interactions	1	1427.5×	0.001	IHH
Activation of SMO	1	634.4×	0.002	IHH
Hedgehog ligand biogenesis	1	211.5×	0.006	IHH
Class B/2 (Secretin family receptors)	1	190.3×	0.006	IHH
Hedgehog ‘on’ state	1	158.6×	0.006	IHH

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
vitelline membrane formation	1	16852.0×	0.001	IHH
negative regulation of eye pigmentation	1	16852.0×	0.001	IHH
camera-type eye photoreceptor cell fate commitment	1	16852.0×	0.001	IHH
intein-mediated protein splicing	1	8426.0×	0.002	IHH
negative regulation of alpha-beta T cell differentiation	1	5617.3×	0.002	IHH
embryonic skeletal joint development	1	3370.4×	0.002	IHH
chondrocyte differentiation involved in endochondral bone morphogenesis	1	2808.7×	0.002	IHH
negative regulation of T cell differentiation in thymus	1	2808.7×	0.002	IHH
negative regulation of immature T cell proliferation in thymus	1	2808.7×	0.002	IHH
head morphogenesis	1	2106.5×	0.002	IHH
proteoglycan metabolic process	1	1872.4×	0.002	IHH
retinal pigment epithelium development	1	1685.2×	0.002	IHH
positive regulation of alpha-beta T cell differentiation	1	1685.2×	0.002	IHH
positive regulation of T cell differentiation in thymus	1	1532.0×	0.002	IHH
self proteolysis	1	1532.0×	0.002	IHH
epithelial cell-cell adhesion	1	1203.7×	0.002	IHH
embryonic camera-type eye morphogenesis	1	1123.5×	0.002	IHH
somite development	1	1123.5×	0.002	IHH
chondrocyte proliferation	1	1053.2×	0.002	IHH
smooth muscle tissue development	1	1053.2×	0.002	IHH
epithelial cell morphogenesis	1	936.2×	0.002	IHH
regulation of growth	1	936.2×	0.002	IHH
embryonic digestive tract morphogenesis	1	936.2×	0.002	IHH
maternal process involved in female pregnancy	1	936.2×	0.002	IHH
pancreas development	1	674.1×	0.003	IHH
negative regulation of chondrocyte differentiation	1	674.1×	0.003	IHH
protein autoprocessing	1	648.1×	0.003	IHH
positive regulation of collagen biosynthetic process	1	648.1×	0.003	IHH
positive regulation of mesenchymal cell proliferation	1	601.9×	0.003	IHH
bone resorption	1	581.1×	0.003	IHH

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
IHH	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	IHH

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)
IHH	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.