Short-rib thoracic dysplasia 10 with or without polydactyly

Summary

Short-rib thoracic dysplasia 10 with or without polydactyly (MONDO:0014284) is a disease caused by IFT172 (GenCC Definitive), with 4 cohort genes.

At a glance

• Causal gene: IFT172 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 1,631

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	short-rib thoracic dysplasia 10 with or without polydactyly
Mondo ID	MONDO:0014284
OMIM	615630
DOID	DOID:0110091
UMLS	C3810175
MedGen	816505
GARD	0015993
Is cancer (heuristic)	no

Also known as: short-rib thoracic dysplasia 10 with or without polydactyly · SRTD10

Data availability: 1,631 ClinVar variants · 3 GenCC gene-disease records.

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 10 with or without 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 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 20 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

600 retrieved; paginated sample, class counts are floors:

291 uncertain significance, 234 likely benign, 39 conflicting classifications of pathogenicity, 14 pathogenic, 8 likely pathogenic, 7 pathogenic/likely pathogenic, 5 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068458	NM_015662.3(IFT172):c.3793G>T (p.Glu1265Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069553	NM_015662.3(IFT172):c.4508G>A (p.Trp1503Ter)	IFT172	Pathogenic	criteria provided, single submitter
1070963	NM_015662.3(IFT172):c.4853del (p.Ser1618fs)	IFT172	Pathogenic	criteria provided, single submitter
1071120	NM_015662.3(IFT172):c.2567del (p.Leu856fs)	IFT172	Pathogenic	criteria provided, single submitter
1071329	NM_015662.3(IFT172):c.4680_4683del (p.Ser1561fs)	IFT172	Pathogenic	criteria provided, single submitter
1074967	NM_015662.3(IFT172):c.3944G>A (p.Trp1315Ter)	IFT172	Pathogenic	criteria provided, single submitter
1075988	NM_015662.3(IFT172):c.2646C>A (p.Cys882Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076916	NM_015662.3(IFT172):c.3949A>T (p.Lys1317Ter)	IFT172	Pathogenic	criteria provided, single submitter
1179103	NM_015662.3(IFT172):c.1342_1343del (p.Arg448fs)	IFT172	Pathogenic	criteria provided, multiple submitters, no conflicts
1355657	NM_015662.3(IFT172):c.1078del (p.Glu359_Val360insTer)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1362201	NM_015662.3(IFT172):c.2866C>T (p.Gln956Ter)	IFT172	Pathogenic	criteria provided, single submitter
1365957	NM_015662.3(IFT172):c.4597dup (p.Thr1533fs)	IFT172	Pathogenic	criteria provided, single submitter
1390470	NM_015662.3(IFT172):c.1209del (p.Phe403fs)	IFT172	Pathogenic	criteria provided, single submitter
1394651	NM_015662.3(IFT172):c.4519C>T (p.Arg1507Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1431370	NM_015662.3(IFT172):c.4194dup (p.Phe1399fs)	IFT172	Pathogenic	criteria provided, single submitter
1451190	NM_015662.3(IFT172):c.1115dup (p.His372fs)	IFT172	Pathogenic	criteria provided, single submitter
1452074	NM_015662.3(IFT172):c.2078del (p.Lys693fs)	IFT172	Pathogenic	criteria provided, single submitter
1455123	NM_015662.3(IFT172):c.5044C>T (p.Arg1682Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456416	NM_015662.3(IFT172):c.2536C>T (p.Arg846Ter)	IFT172	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457968	NM_015662.3(IFT172):c.2146C>T (p.Gln716Ter)	IFT172	Pathogenic	criteria provided, single submitter
1073662	NM_015662.3(IFT172):c.4789dup (p.Leu1597fs)	KRTCAP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066130	NM_015662.3(IFT172):c.910-2A>G	IFT172	Likely pathogenic	criteria provided, single submitter
1067864	NM_015662.3(IFT172):c.5069-2A>G	IFT172	Likely pathogenic	criteria provided, single submitter
1348759	NM_015662.3(IFT172):c.184-2A>C	IFT172	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1469425	NM_015662.3(IFT172):c.2521+1G>T	IFT172	Likely pathogenic	criteria provided, single submitter
1487038	NM_015662.3(IFT172):c.402+2T>G	IFT172	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1515269	NM_015662.3(IFT172):c.3952-1G>C	IFT172	Likely pathogenic	criteria provided, single submitter
1516850	NM_015662.3(IFT172):c.4311+1G>A	IFT172	Likely pathogenic	criteria provided, single submitter
1524924	NM_015662.3(IFT172):c.4815+2_4815+3del	IFT172	Likely pathogenic	criteria provided, single submitter
1000135	NM_015662.3(IFT172):c.4908T>G (p.His1636Gln)	IFT172	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 7 · 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
IFT172	Definitive	Autosomal recessive	short-rib thoracic dysplasia 10 with or without polydactyly	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFT172	Orphanet:110	Bardet-Biedl syndrome
IFT172	Orphanet:140969	Saldino-Mainzer syndrome
IFT172	Orphanet:474	Jeune syndrome
IFT172	Orphanet:791	Retinitis pigmentosa
IFT80	Orphanet:474	Jeune syndrome
IFT80	Orphanet:93268	Short rib-polydactyly syndrome, Beemer-Langer type
IFT80	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IFT172	HGNC:30391	ENSG00000138002	Q9UG01	Intraflagellar transport protein 172 homolog	gencc,clinvar
FNDC4	HGNC:20239	ENSG00000115226	Q9H6D8	Fibronectin type III domain-containing protein 4	clinvar
KRTCAP3	HGNC:28943	ENSG00000157992	Q53RY4	Keratinocyte-associated protein 3	clinvar
IFT80	HGNC:29262	ENSG00000068885	Q9P2H3	Intraflagellar transport protein 80 homolog	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFT172	Intraflagellar transport protein 172 homolog	Required for the maintenance and formation of cilia.
FNDC4	Fibronectin type III domain-containing protein 4	Has anti-inflammatory properties.
IFT80	Intraflagellar transport protein 80 homolog	Component of the intraflagellar transport (IFT) complex B, which is essential for the development and maintenance of motile and sensory cilia.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.25

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	2	8.6×	0.056
Antibody/Immunoglobulin	1	7.3×	0.195
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IFT172	Scaffold/PPI	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_sf
FNDC4	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, FN3_sf
KRTCAP3	Other/Unknown	no		Beta-casein-like
IFT80	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	2
bronchial epithelial cell	1
left testis	1
left adrenal gland	1
left adrenal gland cortex	1
right adrenal gland	1
mucosa of transverse colon	1
pancreatic ductal cell	1
colonic epithelium	1
endothelial cell	1
oviduct epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFT172	236	ubiquitous	marker	right uterine tube, bronchial epithelial cell, left testis
FNDC4	208	ubiquitous	marker	left adrenal gland cortex, left adrenal gland, right adrenal gland
KRTCAP3	197	broad	marker	mucosa of transverse colon, pancreatic ductal cell, right uterine tube
IFT80	256	ubiquitous	marker	colonic epithelium, oviduct epithelium, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFT80	2,582
IFT172	1,922
KRTCAP3	639
FNDC4	615

Intra-cohort edges

A	B	Sources
FNDC4	KRTCAP3	string_interaction
IFT172	IFT80	biogrid_interaction, intact, string_interaction

Structural data

PDB: 1 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFT172	Q9UG01	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IFT80	Q9P2H3	92.50
KRTCAP3	Q53RY4	76.17
FNDC4	Q9H6D8	70.27

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 4 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
Intraflagellar transport	2	200.3×	5e-05	IFT172, IFT80
Hedgehog ‘off’ state	1	89.2×	0.011	IFT172

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
intraciliary anterograde transport	2	591.3×	2e-04	IFT172, IFT80
negative regulation of keratinocyte proliferation	2	468.1×	2e-04	IFT172, IFT80
keratinocyte proliferation	2	387.4×	2e-04	IFT172, IFT80
limb development	2	274.0×	2e-04	IFT172, IFT80
non-motile cilium assembly	2	193.7×	4e-04	IFT172, IFT80
smoothened signaling pathway	2	120.8×	8e-04	IFT172, IFT80
hindgut development	1	5617.3×	0.001	IFT172
growth plate cartilage chondrocyte differentiation	1	1404.3×	0.003	IFT80
response to inositol	1	1404.3×	0.003	IFT80
tooth eruption	1	1123.5×	0.003	IFT80
receptor localization to non-motile cilium	1	1123.5×	0.003	IFT80
cartilage homeostasis	1	1123.5×	0.003	IFT80
negative regulation of non-canonical Wnt signaling pathway	1	1123.5×	0.003	IFT80
cilium assembly	2	49.1×	0.003	IFT172, IFT80
bone mineralization involved in bone maturation	1	936.2×	0.004	IFT80
articular cartilage development	1	802.5×	0.004	IFT80
odontoblast differentiation	1	702.2×	0.004	IFT80
response to transforming growth factor beta	1	624.1×	0.005	FNDC4
osteoblast proliferation	1	468.1×	0.006	IFT80
left/right axis specification	1	401.2×	0.007	IFT172
embryonic camera-type eye morphogenesis	1	374.5×	0.007	IFT172
spinal cord motor neuron differentiation	1	312.1×	0.008	IFT172
proteasomal protein catabolic process	1	255.3×	0.009	IFT80
non-canonical Wnt signaling pathway	1	193.7×	0.011	IFT80
intraciliary transport	1	187.2×	0.011	IFT172
endochondral ossification	1	181.2×	0.011	IFT80
spinal cord development	1	170.2×	0.012	IFT80
negative regulation of smoothened signaling pathway	1	151.8×	0.012	IFT172
dorsal/ventral pattern formation	1	140.4×	0.013	IFT172
positive regulation of smoothened signaling pathway	1	140.4×	0.013	IFT172

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 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
IFT172	0	0
FNDC4	0	0
KRTCAP3	0	0
IFT80	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	1	FNDC4
E	Difficult family or no structure, no drug	3	IFT172, KRTCAP3, IFT80

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
IFT172	0	—
FNDC4	0	—
KRTCAP3	0	—
IFT80	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.