Short-rib thoracic dysplasia 7/20 with polydactyly, digenic

Summary

Short-rib thoracic dysplasia 7/20 with polydactyly, digenic (MONDO:0800356) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	short-rib thoracic dysplasia 7/20 with polydactyly, digenic
Mondo ID	MONDO:0800356
UMLS	C4747658
MedGen	1662086
GARD	0026519
Is cancer (heuristic)	no

Also known as: SRTD7/20

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › short rib dysplasia › short-rib thoracic dysplasia 7/20 with polydactyly, digenic

Related subtypes (7): thoracolaryngopelvic dysplasia, orofaciodigital syndrome type II, orofaciodigital syndrome IV, thoracomelic dysplasia, axial spondylometaphyseal dysplasia, NEK9-related lethal skeletal dysplasia, short rib-polydactyly 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

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
504483	NM_015693.4(INTU):c.826C>T (p.Gln276Ter)	INTU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
446644	NM_020779.4(WDR35):c.932G>T (p.Trp311Leu)	WDR35	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WDR35	Orphanet:1515	Cranioectodermal dysplasia
WDR35	Orphanet:498497	Short rib-polydactyly syndrome type 5
WDR35	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
INTU	HGNC:29239	ENSG00000164066	Q9ULD6	Protein inturned	clinvar
WDR35	HGNC:29250	ENSG00000118965	Q9P2L0	WD repeat-containing protein 35	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
INTU	Protein inturned	Plays a key role in ciliogenesis and embryonic development.
WDR35	WD repeat-containing protein 35	As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in ciliogenesis and ciliary protein trafficking.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 0 · 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
Scaffold/PPI	1	8.6×	0.225
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
INTU	Scaffold/PPI	no		PDZ, PDZ_sf, INTU
WDR35	Transcription factor	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WDR35

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	2
right uterine tube	1
ventricular zone	1
bronchus	1
mucosa of paranasal sinus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
INTU	226	ubiquitous	marker	right uterine tube, bronchial epithelial cell, ventricular zone
WDR35	257	ubiquitous	marker	bronchial epithelial cell, mucosa of paranasal sinus, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
INTU	2,947
WDR35	1,032

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
INTU	Q9ULD6	4
WDR35	Q9P2L0	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Hedgehog ‘off’ state	2	178.4×	1e-04	INTU, WDR35
Intraflagellar transport	1	100.2×	0.014	WDR35
Signaling by Hedgehog	1	92.1×	0.014	INTU
Signal Transduction	1	5.1×	0.187	INTU

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
intraciliary transport	2	561.7×	8e-05	INTU, WDR35
cilium assembly	2	73.6×	0.002	INTU, WDR35
tongue morphogenesis	1	1685.2×	0.005	INTU
negative regulation of cell division	1	1203.7×	0.005	INTU
spinal cord dorsal/ventral patterning	1	1053.2×	0.005	INTU
regulation of ossification	1	601.9×	0.006	INTU
intraciliary retrograde transport	1	561.7×	0.006	WDR35
establishment of planar polarity	1	526.6×	0.006	INTU
negative regulation of keratinocyte proliferation	1	351.1×	0.007	INTU
regulation of smoothened signaling pathway	1	312.1×	0.007	INTU
regulation of cilium assembly	1	300.9×	0.007	INTU
motile cilium assembly	1	290.6×	0.007	INTU
neural tube development	1	263.3×	0.007	INTU
hair follicle morphogenesis	1	247.8×	0.007	INTU
positive regulation of smoothened signaling pathway	1	210.7×	0.008	INTU
limb development	1	205.5×	0.008	INTU
protein localization to cilium	1	200.6×	0.008	WDR35
embryonic digit morphogenesis	1	150.5×	0.009	INTU
non-motile cilium assembly	1	145.3×	0.009	INTU
keratinocyte differentiation	1	123.9×	0.010	INTU
roof of mouth development	1	123.9×	0.010	INTU
smoothened signaling pathway	1	90.6×	0.013	INTU
cellular response to leukemia inhibitory factor	1	79.5×	0.014	WDR35
vesicle-mediated transport	1	48.1×	0.022	INTU
cell division	1	23.1×	0.043	INTU
nervous system development	1	23.0×	0.043	INTU

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
INTU	0	0
WDR35	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	INTU, WDR35

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
INTU	0	—
WDR35	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.