Short-rib thoracic dysplasia 20 with polydactyly

Summary

Short-rib thoracic dysplasia 20 with polydactyly (MONDO:0044328) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	short-rib thoracic dysplasia 20 with polydactyly
Mondo ID	MONDO:0044328
OMIM	617925
UMLS	C4693616
MedGen	1634931
GARD	0025897
Is cancer (heuristic)	no

Also known as: short-rib thoracic dysplasia 20 with polydactyly · SRTD20

Data availability: 11 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 › ciliopathy › Jeune syndrome › short-rib thoracic dysplasia 20 with polydactyly

Related subtypes (23): asphyxiating thoracic dystrophy 1, Ellis-van Creveld syndrome, short-rib thoracic dysplasia 6 with or without polydactyly, short-rib thoracic dysplasia 9 with or without polydactyly, Beemer-Langer syndrome, asphyxiating thoracic dystrophy 2, asphyxiating thoracic dystrophy 3, asphyxiating thoracic dystrophy 4, short-rib thoracic dysplasia 7 with or without polydactyly, asphyxiating thoracic dystrophy 5, short-rib thoracic dysplasia 8 with or without polydactyly, short-rib thoracic dysplasia 10 with or without polydactyly, short-rib thoracic dysplasia 11 with or without polydactyly, short-rib thoracic dysplasia 13 with or without polydactyly, short-rib thoracic dysplasia 14 with polydactyly, short-rib thoracic dysplasia 15 with polydactyly, short-rib thoracic dysplasia 16 with or without polydactyly, short-rib thoracic dysplasia 21 without polydactyly, short-rib thoracic dysplasia 19 with or without polydactyly, short-rib thoracic dysplasia 18 with polydactyly, short-rib thoracic dysplasia 17 with or without polydactyly, Jeune syndrome - GRK2-related, short-rib thoracic dysplasia 22 without polydactyly

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

11 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1694472	NM_015693.4(INTU):c.2358_2359dup (p.Asn787fs)	INTU	Pathogenic	criteria provided, single submitter
1341890	NM_015693.4(INTU):c.1305dup (p.Asn436Ter)	INTU	Likely pathogenic	criteria provided, single submitter
504481	NM_015693.4(INTU):c.1063G>T (p.Glu355Ter)	INTU	Likely pathogenic	criteria provided, single submitter
504482	NM_015693.4(INTU):c.1499A>C (p.Glu500Ala)	INTU	Likely pathogenic	criteria provided, single submitter
2713590	NM_015693.4(INTU):c.469C>T (p.Arg157Ter)	INTU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
504483	NM_015693.4(INTU):c.826C>T (p.Gln276Ter)	INTU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1694474	NM_015693.4(INTU):c.2527C>T (p.Arg843Cys)	INTU	Uncertain significance	criteria provided, multiple submitters, no conflicts
1179813	NM_015693.4(INTU):c.813G>A (p.Thr271=)	INTU	Benign	criteria provided, multiple submitters, no conflicts
1249414	NM_015693.4(INTU):c.471A>G (p.Arg157=)	INTU	Benign	criteria provided, multiple submitters, no conflicts
1644449	NM_015693.4(INTU):c.683-16G>C	INTU	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
780934	NM_015693.4(INTU):c.1450-9T>G	INTU	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
INTU	Limited	Unknown	short-rib thoracic dysplasia 20 with polydactyly	4

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
INTU	HGNC:29239	ENSG00000164066	Q9ULD6	Protein inturned	gencc,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.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
INTU	Scaffold/PPI	no		PDZ, PDZ_sf, INTU

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
bronchial epithelial cell	1
right uterine tube	1
ventricular zone	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
INTU	2,947

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
INTU	Q9ULD6	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Signaling by Hedgehog	1	184.2×	0.008	INTU
Hedgehog ‘off’ state	1	178.4×	0.008	INTU
Signal Transduction	1	10.2×	0.098	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tongue morphogenesis	1	3370.4×	0.004	INTU
negative regulation of cell division	1	2407.4×	0.004	INTU
spinal cord dorsal/ventral patterning	1	2106.5×	0.004	INTU
regulation of ossification	1	1203.7×	0.004	INTU
establishment of planar polarity	1	1053.2×	0.004	INTU
negative regulation of keratinocyte proliferation	1	702.2×	0.004	INTU
regulation of smoothened signaling pathway	1	624.1×	0.004	INTU
regulation of cilium assembly	1	601.9×	0.004	INTU
motile cilium assembly	1	581.1×	0.004	INTU
intraciliary transport	1	561.7×	0.004	INTU
neural tube development	1	526.6×	0.004	INTU
hair follicle morphogenesis	1	495.6×	0.004	INTU
positive regulation of smoothened signaling pathway	1	421.3×	0.004	INTU
limb development	1	411.0×	0.004	INTU
embryonic digit morphogenesis	1	300.9×	0.005	INTU
non-motile cilium assembly	1	290.6×	0.005	INTU
keratinocyte differentiation	1	247.8×	0.005	INTU
roof of mouth development	1	247.8×	0.005	INTU
smoothened signaling pathway	1	181.2×	0.007	INTU
vesicle-mediated transport	1	96.3×	0.012	INTU
cilium assembly	1	73.6×	0.015	INTU
cell division	1	46.2×	0.022	INTU
nervous system development	1	45.9×	0.022	INTU

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
INTU	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	INTU

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)
INTU	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.