Short-rib thoracic dysplasia 19 with or without polydactyly

Summary

Short-rib thoracic dysplasia 19 with or without polydactyly (MONDO:0033485) is a disease caused by IFT81 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: IFT81 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	short-rib thoracic dysplasia 19 with or without polydactyly
Mondo ID	MONDO:0033485
OMIM	617895
DOID	DOID:0080295
UMLS	C4693524
MedGen	1635837
GARD	0025803
Is cancer (heuristic)	no

Also known as: short-rib thoracic dysplasia 19 with or without polydactyly · SRTD19

Data availability: 17 ClinVar variants · 2 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 19 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 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 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

17 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 4 pathogenic, 4 likely pathogenic, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027824	NM_014055.4(IFT81):c.1717-2A>G	IFT81	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323109	NM_014055.4(IFT81):c.190C>T (p.Arg64Ter)	IFT81	Pathogenic	criteria provided, multiple submitters, no conflicts
2691451	NM_014055.4(IFT81):c.1066G>T (p.Glu356Ter)	IFT81	Pathogenic	criteria provided, single submitter
495121	NM_014055.4(IFT81):c.1534C>T (p.Arg512Ter)	IFT81	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
495122	NM_014055.4(IFT81):c.87G>C (p.Leu29Phe)	IFT81	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
560182	Single allele	IFT81	Pathogenic	criteria provided, single submitter
956773	NM_014055.4(IFT81):c.1441C>T (p.Arg481Ter)	IFT81	Pathogenic	criteria provided, single submitter
3779759	NM_014055.4(IFT81):c.1087dup (p.Gln363fs)	IFT81	Likely pathogenic	criteria provided, single submitter
4278139	NM_014055.4(IFT81):c.460_461del (p.Leu154fs)	IFT81	Likely pathogenic	criteria provided, single submitter
495123	NM_014055.4(IFT81):c.785T>G (p.Leu262Ter)	IFT81	Likely pathogenic	criteria provided, single submitter
599486	NM_014055.4(IFT81):c.259C>T (p.Arg87Cys)	IFT81	Likely pathogenic	criteria provided, single submitter
1338762	NM_014055.4(IFT81):c.134T>C (p.Ile45Thr)	IFT81	Uncertain significance	criteria provided, multiple submitters, no conflicts
218893	NM_014055.4(IFT81):c.2015_2019del (p.Asp672fs)	IFT81	Uncertain significance	criteria provided, multiple submitters, no conflicts
3901117	NM_014055.4(IFT81):c.1969C>T (p.Gln657Ter)	IFT81	Uncertain significance	criteria provided, single submitter
495124	NM_014055.4(IFT81):c.1300CTT[1] (p.Leu435del)	IFT81	Uncertain significance	criteria provided, single submitter
963152	NM_014055.4(IFT81):c.917A>T (p.His306Leu)	IFT81	Uncertain significance	criteria provided, multiple submitters, no conflicts
999337	NM_014055.4(IFT81):c.2015A>G (p.Asp672Gly)	IFT81	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
IFT81	Strong	Autosomal recessive	short-rib thoracic dysplasia 19 with or without polydactyly	3

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
IFT81	HGNC:14313	ENSG00000122970	Q8WYA0	Intraflagellar transport protein 81 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFT81	Intraflagellar transport protein 81 homolog	Component of the intraflagellar transport (IFT) complex B: together with IFT74, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium.

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)
IFT81	Other/Unknown	no		IFT81, IFT81_CH, IFT81_N_sf

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
IFT81	273	ubiquitous	marker	bronchial epithelial cell, ventricular zone, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFT81	2,125

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IFT81	Q8WYA0	83.45

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Intraflagellar transport	1	200.3×	0.005	IFT81

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
intraciliary transport involved in cilium assembly	1	2407.4×	0.002	IFT81
intraciliary anterograde transport	1	887.0×	0.002	IFT81
sperm flagellum assembly	1	674.1×	0.002	IFT81
regulation of smoothened signaling pathway	1	624.1×	0.002	IFT81
intraciliary transport	1	561.7×	0.002	IFT81
cilium assembly	1	73.6×	0.016	IFT81
spermatogenesis	1	35.2×	0.028	IFT81

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
IFT81	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	IFT81

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)
IFT81	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.