Short-rib thoracic dysplasia 7 with or without polydactyly

Summary

Short-rib thoracic dysplasia 7 with or without polydactyly (MONDO:0013569) is a disease caused by WDR35 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: WDR35 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 660

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	short-rib thoracic dysplasia 7 with or without polydactyly
Mondo ID	MONDO:0013569
OMIM	614091
Orphanet	498497
DOID	DOID:0110090
UMLS	C3279792
MedGen	481422
GARD	0015756
Is cancer (heuristic)	no

Also known as: short rib-polydactyly syndrome type 5 · short rib-polydactyly syndrome, type 5 · short-rib thoracic dysplasia 7 with or without polydactyly · SRPS5 · SRTD7

Data availability: 660 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 7 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, 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 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:

275 uncertain significance, 173 likely benign, 47 conflicting classifications of pathogenicity, 33 benign, 28 pathogenic, 21 likely pathogenic, 13 benign/likely benign, 10 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072199	NM_020779.4(WDR35):c.2638dup (p.Thr880fs)	WDR35	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075625	NM_020779.4(WDR35):c.1690C>T (p.Arg564Ter)	WDR35	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1360910	NM_020779.4(WDR35):c.1954_1955insAAAC (p.Leu652fs)	WDR35	Pathogenic	criteria provided, single submitter
1368965	NM_020779.4(WDR35):c.1694_1695dup (p.Thr566Ter)	WDR35	Pathogenic	criteria provided, single submitter
1415290	NM_020779.4(WDR35):c.297del (p.Met99fs)	WDR35	Pathogenic	criteria provided, single submitter
1435158	NM_020779.4(WDR35):c.136C>T (p.Gln46Ter)	WDR35	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459665	NC_000002.11:g.(?20153575)(20153759_?)del	WDR35	Pathogenic	criteria provided, single submitter
1978470	NM_020779.4(WDR35):c.2701G>T (p.Glu901Ter)	WDR35	Pathogenic	criteria provided, single submitter
22	NM_020779.4(WDR35):c.2858del (p.Pro953fs)	WDR35	Pathogenic	criteria provided, single submitter
2423459	NC_000002.11:g.(?20188906)(20189063_?)del	WDR35	Pathogenic	criteria provided, single submitter
2631751	NM_020779.4(WDR35):c.524del (p.Met175fs)	WDR35	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
286673	NM_020779.4(WDR35):c.1255+1G>A	WDR35	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
289210	NM_020779.4(WDR35):c.1468del (p.Gln490fs)	WDR35	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2939861	NM_020779.4(WDR35):c.1554C>G (p.Tyr518Ter)	WDR35	Pathogenic	criteria provided, single submitter
2948787	NM_020779.4(WDR35):c.1322G>A (p.Trp441Ter)	WDR35	Pathogenic	criteria provided, single submitter
2951856	NM_020779.4(WDR35):c.1609C>T (p.Gln537Ter)	WDR35	Pathogenic	criteria provided, single submitter
2952744	NM_020779.4(WDR35):c.171_178del (p.Ser59fs)	WDR35	Pathogenic	criteria provided, single submitter
31043	NM_020779.4(WDR35):c.307+214_436+1120del	WDR35	Pathogenic	no assertion criteria provided
31044	NM_020779.4(WDR35):c.1600C>T (p.Arg534Ter)	WDR35	Pathogenic	no assertion criteria provided
31045	NM_020779.4(WDR35):c.781T>C (p.Trp261Arg)	WDR35	Pathogenic	no assertion criteria provided
373022	NM_020779.4(WDR35):c.584_585del (p.Leu195fs)	WDR35	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3751016	NM_020779.4(WDR35):c.2713_2714del (p.Leu905fs)	WDR35	Pathogenic	criteria provided, single submitter
3759851	NM_020779.4(WDR35):c.1714C>T (p.Gln572Ter)	WDR35	Pathogenic	criteria provided, single submitter
3762513	NM_020779.4(WDR35):c.519del (p.Phe173fs)	WDR35	Pathogenic	criteria provided, single submitter
3764724	NM_020779.4(WDR35):c.1137del (p.Thr380fs)	WDR35	Pathogenic	criteria provided, single submitter
431796	NM_020779.4(WDR35):c.206G>A (p.Gly69Asp)	WDR35	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4783901	NM_020779.4(WDR35):c.721_727del (p.His241fs)	WDR35	Pathogenic	criteria provided, single submitter
4785065	NM_020779.4(WDR35):c.2306G>A (p.Trp769Ter)	WDR35	Pathogenic	criteria provided, single submitter
4788990	NM_020779.4(WDR35):c.2956del (p.Ser986fs)	WDR35	Pathogenic	criteria provided, single submitter
4793548	NM_020779.4(WDR35):c.1525-2_1527dup	WDR35	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · 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
WDR35	Definitive	Autosomal recessive	cranioectodermal dysplasia 2	8

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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WDR35	HGNC:29250	ENSG00000118965	Q9P2L0	WD repeat-containing protein 35	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 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)
WDR35	Transcription factor	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WDR35

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
bronchus	1
mucosa of paranasal sinus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
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
WDR35	1,032

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WDR35	Q9P2L0	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	WDR35
Hedgehog ‘off’ state	1	178.4×	0.006	WDR35

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 retrograde transport	1	1123.5×	0.004	WDR35
intraciliary transport	1	561.7×	0.004	WDR35
protein localization to cilium	1	401.2×	0.004	WDR35
cellular response to leukemia inhibitory factor	1	159.0×	0.008	WDR35
cilium assembly	1	73.6×	0.014	WDR35

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
WDR35	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	WDR35

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)
WDR35	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.