Autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome

Summary

Autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome (MONDO:0018777) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

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

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome
Mondo ID	MONDO:0018777
Orphanet	476119
UMLS	C5568802
MedGen	1800225
GARD	0021953
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › disorder of pilosebaceous unit › hypertrichosis › autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome

Related subtypes (10): hypertrichosis of eyelid, gingival fibromatosis-hypertrichosis syndrome, hypertrichosis cubiti-short stature syndrome, cataract-hypertrichosis-intellectual disability syndrome, cervical hypertrichosis-peripheral neuropathy syndrome, Rabson-Mendenhall syndrome, isolated anterior cervical hypertrichosis, acquired hypertrichosis lanuginosa, hypertrichosis lanuginosa congenita, hypertrichosis-acromegaloid facial appearance syndrome

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 13 · 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
SHH	Definitive	Autosomal dominant	polydactyly of a triphalangeal thumb	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SHH	Orphanet:220386	Semilobar holoprosencephaly
SHH	Orphanet:280195	Septopreoptic holoprosencephaly
SHH	Orphanet:280200	Microform holoprosencephaly
SHH	Orphanet:476119	Autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome
SHH	Orphanet:485275	Acquired schizencephaly
SHH	Orphanet:93321	Isolated radial hemimelia
SHH	Orphanet:93336	Polydactyly of a triphalangeal thumb
SHH	Orphanet:93405	Syndactyly type 4
SHH	Orphanet:93924	Lobar holoprosencephaly
SHH	Orphanet:93925	Alobar holoprosencephaly
SHH	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
SHH	Orphanet:988	Tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome
SHH	Orphanet:98938	Colobomatous microphthalmia

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
SHH	HGNC:10848	ENSG00000164690	Q15465	Sonic hedgehog protein	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SHH	Sonic hedgehog protein	The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity.

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)
SHH	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
buccal mucosa cell	1
epithelial cell of pancreas	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SHH	131	broad	marker	buccal mucosa cell, right lobe of liver, epithelial cell of pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SHH	4,953

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SHH	Q15465	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. 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×	0.003	SHH
Formation of lateral plate mesoderm	1	2284.0×	0.003	SHH
Release of Hh-Np from the secreting cell	1	1427.5×	0.003	SHH
Hh mutants abrogate ligand secretion	1	1427.5×	0.003	SHH
Ligand-receptor interactions	1	1427.5×	0.003	SHH
Formation of axial mesoderm	1	815.7×	0.004	SHH
Activation of SMO	1	634.4×	0.005	SHH
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	601.0×	0.005	SHH
Developmental Lineage of Pancreatic Acinar Cells	1	300.5×	0.008	SHH
Gastrulation	1	259.6×	0.008	SHH
Hh mutants are degraded by ERAD	1	243.0×	0.008	SHH
Developmental Cell Lineages	1	223.9×	0.008	SHH
Hedgehog ligand biogenesis	1	211.5×	0.008	SHH
Class B/2 (Secretin family receptors)	1	190.3×	0.008	SHH
Signaling by Hedgehog	1	184.2×	0.008	SHH
Hedgehog ‘on’ state	1	158.6×	0.009	SHH
GPCR ligand binding	1	64.2×	0.020	SHH
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.022	SHH
Signaling by GPCR	1	40.1×	0.029	SHH
Developmental Biology	1	14.5×	0.076	SHH
Disease	1	13.1×	0.080	SHH
Signal Transduction	1	10.2×	0.098	SHH

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
polarity specification of anterior/posterior axis	1	16852.0×	7e-04	SHH
trachea morphogenesis	1	16852.0×	7e-04	SHH
right lung development	1	16852.0×	7e-04	SHH
left lung development	1	16852.0×	7e-04	SHH
primary prostatic bud elongation	1	16852.0×	7e-04	SHH
regulation of prostatic bud formation	1	16852.0×	7e-04	SHH
obsolete regulation of mesenchymal cell proliferation involved in prostate gland development	1	16852.0×	7e-04	SHH
mesenchymal smoothened signaling pathway involved in prostate gland development	1	16852.0×	7e-04	SHH
positive regulation of sclerotome development	1	16852.0×	7e-04	SHH
tracheoesophageal septum formation	1	16852.0×	7e-04	SHH
negative regulation of ureter smooth muscle cell differentiation	1	16852.0×	7e-04	SHH
positive regulation of ureter smooth muscle cell differentiation	1	16852.0×	7e-04	SHH
negative regulation of kidney smooth muscle cell differentiation	1	16852.0×	7e-04	SHH
positive regulation of kidney smooth muscle cell differentiation	1	16852.0×	7e-04	SHH
positive regulation of skeletal muscle cell proliferation	1	8426.0×	1e-03	SHH
intein-mediated protein splicing	1	8426.0×	1e-03	SHH
trunk neural crest cell migration	1	8426.0×	1e-03	SHH
regulation of nodal signaling pathway	1	8426.0×	1e-03	SHH
positive regulation of mesenchymal cell proliferation involved in ureter development	1	8426.0×	1e-03	SHH
ventral midline development	1	5617.3×	0.001	SHH
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	1	5617.3×	0.001	SHH
negative regulation of alpha-beta T cell differentiation	1	5617.3×	0.001	SHH
regulation of glial cell proliferation	1	5617.3×	0.001	SHH
bud outgrowth involved in lung branching	1	5617.3×	0.001	SHH
prostate epithelial cord elongation	1	5617.3×	0.001	SHH
positive regulation of epithelial cell proliferation involved in prostate gland development	1	5617.3×	0.001	SHH
metanephric mesenchymal cell proliferation involved in metanephros development	1	5617.3×	0.001	SHH
hindgut morphogenesis	1	4213.0×	0.001	SHH
formation of anatomical boundary	1	4213.0×	0.001	SHH
epithelial-mesenchymal cell signaling	1	4213.0×	0.001	SHH

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SHH	VISMODEGIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SHH	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VISMODEGIB	4	SHH

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SHH	27	Binding:23, Functional:4

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
VISMODEGIB	4	SHH

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SHH
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	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.