Cranioectodermal dysplasia 3

Summary

Cranioectodermal dysplasia 3 (MONDO:0013573) is a disease caused by IFT43 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: IFT43 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 75

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cranioectodermal dysplasia 3
Mondo ID	MONDO:0013573
OMIM	614099
DOID	DOID:0080805
UMLS	C3279807
MedGen	481437
GARD	0015757
Is cancer (heuristic)	no

Also known as: CED3 · cranioectodermal dysplasia 3 · cranioectodermal dysplasia caused by mutation in IFT43 · Cranioectodermal dysplasia type 3 · IFT43 cranioectodermal dysplasia

Data availability: 75 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 › autosomal genetic disease › autosomal recessive disease › craniosynostosis syndrome, autosomal recessive › cranioectodermal dysplasia › cranioectodermal dysplasia 3

Related subtypes (6): cranioectodermal dysplasia 2, cranioectodermal dysplasia 4, short-rib thoracic dysplasia 16 with or without polydactyly, cranioectodermal dysplasia 1, cranioectodermal dysplasia 5, cranioectodermal dysplasia 6

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

75 retrieved; paginated sample, class counts are floors:

39 uncertain significance, 10 likely benign, 10 likely pathogenic, 8 conflicting classifications of pathogenicity, 3 benign, 2 pathogenic, 2 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1328283	NM_001102564.3(IFT43):c.328C>T (p.Gln110Ter)	IFT43	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31098	NM_001102564.3(IFT43):c.1A>G (p.Met1Val)	IFT43	Pathogenic	criteria provided, single submitter
4277718	NM_001102564.3(IFT43):c.296-5634_296-5633del	IFT43	Pathogenic	criteria provided, single submitter
1513672	NM_001102564.3(IFT43):c.148-2A>C	IFT43	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3576768	NM_001102564.3(IFT43):c.20T>A (p.Leu7Ter)	IFT43	Likely pathogenic	criteria provided, single submitter
3576770	NM_001102564.3(IFT43):c.55del (p.Arg19fs)	IFT43	Likely pathogenic	criteria provided, single submitter
3576774	NM_001102564.3(IFT43):c.164T>A (p.Leu55Ter)	IFT43	Likely pathogenic	criteria provided, single submitter
3576775	NM_001102564.3(IFT43):c.175C>T (p.Arg59Ter)	IFT43	Likely pathogenic	criteria provided, single submitter
3576781	NM_001102564.3(IFT43):c.368+1G>A	IFT43	Likely pathogenic	criteria provided, single submitter
3576782	NM_001102564.3(IFT43):c.477del (p.Val160fs)	IFT43	Likely pathogenic	criteria provided, single submitter
4849281	NM_001102564.3(IFT43):c.507+1G>A	IFT43	Likely pathogenic	criteria provided, single submitter
4849485	NM_001102564.3(IFT43):c.368+1G>C	IFT43	Likely pathogenic	criteria provided, single submitter
631717	NM_001102564.3(IFT43):c.214_215+2del	IFT43	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1089443	NM_001102564.3(IFT43):c.201C>T (p.Ser67=)	IFT43	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1954624	NM_001102564.3(IFT43):c.296-5686_296-5685del	IFT43	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2958638	NM_001102564.3(IFT43):c.369-11C>A	IFT43	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
489395	NM_001102564.3(IFT43):c.100G>A (p.Glu34Lys)	IFT43	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
596041	NM_001102564.3(IFT43):c.296-5602T>C	IFT43	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
749406	NM_001102564.3(IFT43):c.468C>T (p.Leu156=)	IFT43	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
807149	NM_001102564.3(IFT43):c.16G>C (p.Asp6His)	IFT43	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
849336	NM_001102564.3(IFT43):c.395A>T (p.Tyr132Phe)	IFT43	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1005665	NM_001102564.3(IFT43):c.540C>A (p.Phe180Leu)	IFT43	Uncertain significance	criteria provided, multiple submitters, no conflicts
1016616	NM_001102564.3(IFT43):c.365C>T (p.Pro122Leu)	IFT43	Uncertain significance	criteria provided, multiple submitters, no conflicts
1021274	NM_001102564.3(IFT43):c.469C>A (p.Leu157Ile)	IFT43	Uncertain significance	criteria provided, multiple submitters, no conflicts
1022483	NM_001102564.3(IFT43):c.605C>T (p.Ala202Val)	IFT43	Uncertain significance	criteria provided, multiple submitters, no conflicts
1024679	NM_001102564.3(IFT43):c.517G>A (p.Gly173Ser)	IFT43	Uncertain significance	criteria provided, multiple submitters, no conflicts
1035347	NM_001102564.3(IFT43):c.104A>G (p.Asn35Ser)	IFT43	Uncertain significance	criteria provided, multiple submitters, no conflicts
1047308	NM_001102564.3(IFT43):c.397C>T (p.Arg133Cys)	IFT43	Uncertain significance	criteria provided, multiple submitters, no conflicts
1347419	NM_001102564.3(IFT43):c.587C>T (p.Thr196Met)	IFT43	Uncertain significance	criteria provided, multiple submitters, no conflicts
1370314	NM_001102564.3(IFT43):c.502C>T (p.Arg168Trp)	IFT43	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · 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
IFT43	Strong	Autosomal recessive	short-rib thoracic dysplasia 18 with polydactyly	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFT43	Orphanet:1515	Cranioectodermal dysplasia
IFT43	Orphanet:791	Retinitis pigmentosa

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
IFT43	HGNC:29669	ENSG00000119650	Q96FT9	Intraflagellar transport protein 43 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFT43	Intraflagellar transport protein 43 homolog	As a component of 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.

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)
IFT43	Other/Unknown	no		IFT43

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
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFT43	252	ubiquitous	marker	right uterine tube, bronchial epithelial cell, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFT43	635

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFT43	Q96FT9	3

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	IFT43

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×	0.002	IFT43
cilium assembly	1	73.6×	0.014	IFT43

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
IFT43	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	IFT43

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)
IFT43	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.