Asphyxiating thoracic dystrophy 5

Summary

Asphyxiating thoracic dystrophy 5 (MONDO:0013717) is a disease caused by WDR19 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: WDR19 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 1,161

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	asphyxiating thoracic dystrophy 5
Mondo ID	MONDO:0013717
OMIM	614376
DOID	DOID:0110089
UMLS	C3280598
MedGen	482228
GARD	0015795
Is cancer (heuristic)	no

Also known as: asphyxiating thoracic dystrophy 5 · asphyxiating thoracic dystrophy type 5 · ATD5 · Jeune syndrome caused by mutation in WDR19 · short-rib thoracic dysplasia 5 with or without polydactyly · SRTD5 · WDR19 Jeune syndrome

Data availability: 1,161 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 › asphyxiating thoracic dystrophy 5

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, 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 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:

298 uncertain significance, 241 likely benign, 19 pathogenic, 12 conflicting classifications of pathogenicity, 10 likely pathogenic, 9 pathogenic/likely pathogenic, 8 benign, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068591	NM_025132.4(WDR19):c.2351_2361del (p.Gln784fs)	WDR19	Pathogenic	criteria provided, single submitter
1071241	NM_025132.4(WDR19):c.388C>T (p.Arg130Ter)	WDR19	Pathogenic	criteria provided, single submitter
1071987	NM_025132.4(WDR19):c.1122_1123insT (p.Pro375fs)	WDR19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073132	NM_025132.4(WDR19):c.1911_1914del (p.Phe637fs)	WDR19	Pathogenic	criteria provided, single submitter
1179139	NM_025132.4(WDR19):c.2601_2602dup (p.Tyr868fs)	WDR19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1213952	NM_025132.4(WDR19):c.2485C>T (p.Arg829Ter)	WDR19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
127154	NM_025132.4(WDR19):c.641dup (p.Leu214fs)	WDR19	Pathogenic	criteria provided, multiple submitters, no conflicts
127157	NM_025132.4(WDR19):c.3703G>A (p.Glu1235Lys)	WDR19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
127158	NM_025132.4(WDR19):c.3533G>A (p.Arg1178Gln)	WDR19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
127159	NM_025132.4(WDR19):c.3565+1G>A	WDR19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1347795	NM_025132.4(WDR19):c.3184-2A>G	WDR19	Pathogenic	criteria provided, single submitter
1382656	NM_025132.4(WDR19):c.3319C>T (p.Gln1107Ter)	WDR19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1401950	NM_025132.4(WDR19):c.2481dup (p.Arg828fs)	WDR19	Pathogenic	criteria provided, single submitter
1446760	NM_025132.4(WDR19):c.632dup (p.Leu211fs)	WDR19	Pathogenic	criteria provided, single submitter
1451170	NM_025132.4(WDR19):c.441G>A (p.Trp147Ter)	WDR19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454330	NC_000004.11:g.(?39184178)(39184203_?)del	WDR19	Pathogenic	criteria provided, single submitter
1456271	NM_025132.4(WDR19):c.234C>A (p.Cys78Ter)	WDR19	Pathogenic	criteria provided, single submitter
1457671	NC_000004.11:g.(?39257448)(39257600_?)del	WDR19	Pathogenic	criteria provided, single submitter
1473602	NM_025132.4(WDR19):c.3184-2A>C	WDR19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2011472	NM_025132.4(WDR19):c.3457del (p.Ile1153fs)	WDR19	Pathogenic	criteria provided, single submitter
2023838	NM_025132.4(WDR19):c.2337del (p.Glu780fs)	WDR19	Pathogenic	criteria provided, single submitter
2041533	NM_025132.4(WDR19):c.526C>T (p.Gln176Ter)	WDR19	Pathogenic	criteria provided, single submitter
2052921	NM_025132.4(WDR19):c.422_423del (p.Arg141fs)	WDR19	Pathogenic	criteria provided, single submitter
2087751	NM_025132.4(WDR19):c.2972del (p.Asn991fs)	WDR19	Pathogenic	criteria provided, single submitter
2090526	NM_025132.4(WDR19):c.2589T>G (p.Tyr863Ter)	WDR19	Pathogenic	criteria provided, single submitter
2102299	NM_025132.4(WDR19):c.697_701dup (p.Val235fs)	WDR19	Pathogenic	criteria provided, single submitter
2104717	NM_025132.4(WDR19):c.2797del (p.Asp933fs)	WDR19	Pathogenic	criteria provided, single submitter
2148838	NM_025132.4(WDR19):c.812del (p.Ala271fs)	WDR19	Pathogenic	criteria provided, single submitter
1066118	NM_025132.4(WDR19):c.1357-2A>T	WDR19	Likely pathogenic	criteria provided, single submitter
1067777	NM_025132.4(WDR19):c.1479+2T>C	WDR19	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 4 · 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
WDR19	Definitive	Autosomal recessive	asphyxiating thoracic dystrophy 5	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WDR19	Orphanet:1515	Cranioectodermal dysplasia
WDR19	Orphanet:3156	Senior-Loken syndrome
WDR19	Orphanet:474	Jeune syndrome
WDR19	Orphanet:93592	Juvenile nephronophthisis

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
WDR19	HGNC:18340	ENSG00000157796	Q8NEZ3	WD repeat-containing protein 19	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WDR19	WD repeat-containing protein 19	As 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 cilia function and/or assembly.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WDR19	Transcription factor	no		WD40_rpt, TPR-like_helical_dom_sf, WD40/YVTN_repeat-like_dom_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
adenohypophysis	1
bronchial epithelial cell	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WDR19	269	ubiquitous	marker	right uterine tube, bronchial epithelial cell, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WDR19	1,251

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WDR19	Q8NEZ3	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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×	0.006	WDR19
Hedgehog ‘off’ state	1	178.4×	0.006	WDR19

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
ear morphogenesis	1	4213.0×	9e-04	WDR19
smoothened signaling pathway involved in dorsal/ventral neural tube patterning	1	4213.0×	9e-04	WDR19
myotome development	1	4213.0×	9e-04	WDR19
digestive system development	1	3370.4×	9e-04	WDR19
protein localization to ciliary membrane	1	3370.4×	9e-04	WDR19
embryonic camera-type eye development	1	1203.7×	0.002	WDR19
nervous system process	1	1203.7×	0.002	WDR19
gonad development	1	1123.5×	0.002	WDR19
intraciliary retrograde transport	1	1123.5×	0.002	WDR19
receptor clustering	1	624.1×	0.003	WDR19
embryonic cranial skeleton morphogenesis	1	581.1×	0.003	WDR19
embryonic limb morphogenesis	1	401.2×	0.003	WDR19
cell morphogenesis	1	157.5×	0.008	WDR19
protein-containing complex assembly	1	113.9×	0.010	WDR19
cilium assembly	1	73.6×	0.014	WDR19
in utero embryonic development	1	72.0×	0.014	WDR19

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
WDR19	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	WDR19

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)
WDR19	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.