Cranioectodermal dysplasia 1

Summary

Cranioectodermal dysplasia 1 (MONDO:0021093) is a disease caused by IFT122 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: IFT122 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 821
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cranioectodermal dysplasia 1
Mondo ID	MONDO:0021093
OMIM	218330
DOID	DOID:0080803
UMLS	C0432235
MedGen	96586
GARD	0025289
Is cancer (heuristic)	no

Also known as: CED1 · cranioectodermal dysplasia 1 · cranioectodermal dysplasia caused by mutation in IFT122 · cranioectodermal dysplasia type 1 · IFT122 cranioectodermal dysplasia · Sensenbrenner syndrome

Data availability: 821 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 › autosomal genetic disease › autosomal recessive disease › craniosynostosis syndrome, autosomal recessive › cranioectodermal dysplasia › cranioectodermal dysplasia 1

Related subtypes (6): cranioectodermal dysplasia 2, cranioectodermal dysplasia 3, cranioectodermal dysplasia 4, short-rib thoracic dysplasia 16 with or without polydactyly, 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

600 retrieved; paginated sample, class counts are floors:

301 uncertain significance, 176 likely benign, 40 conflicting classifications of pathogenicity, 23 pathogenic, 22 benign/likely benign, 20 likely pathogenic, 10 benign, 8 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1179190	NM_052989.3(IFT122):c.2285del (p.Lys762fs)	IFT122	Pathogenic	criteria provided, single submitter
1323102	NM_052989.3(IFT122):c.273-281_273-271del	IFT122	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323103	NM_052989.3(IFT122):c.3426_3430del (p.Ser1143fs)	IFT122	Pathogenic	criteria provided, multiple submitters, no conflicts
1329086	NM_052989.3(IFT122):c.3726A>G (p.Ter1242Trp)	IFT122	Pathogenic	no assertion criteria provided
1368335	NM_052989.3(IFT122):c.2668C>T (p.Arg890Ter)	IFT122	Pathogenic	criteria provided, single submitter
1435502	NM_052989.3(IFT122):c.1432dup (p.Val478fs)	IFT122	Pathogenic	criteria provided, single submitter
1456968	NC_000003.11:g.(?129159174)(129214470_?)del	IFT122	Pathogenic	criteria provided, single submitter
1895969	NM_052989.3(IFT122):c.2313C>A (p.Tyr771Ter)	IFT122	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
191185	NM_052989.3(IFT122):c.2375+2T>C	IFT122	Pathogenic	criteria provided, single submitter
1933293	NM_052989.3(IFT122):c.3013C>T (p.Gln1005Ter)	IFT122	Pathogenic	criteria provided, multiple submitters, no conflicts
1995864	NM_052989.3(IFT122):c.384del (p.Lys128fs)	IFT122	Pathogenic	criteria provided, single submitter
2009853	NM_052989.3(IFT122):c.3180C>A (p.Cys1060Ter)	IFT122	Pathogenic	criteria provided, single submitter
2017547	NM_052989.3(IFT122):c.273-374_273-369dup	IFT122	Pathogenic	criteria provided, single submitter
2033213	NM_052989.3(IFT122):c.347_348del (p.Phe116fs)	IFT122	Pathogenic	criteria provided, single submitter
2038023	NM_052989.3(IFT122):c.273-341dup	IFT122	Pathogenic	criteria provided, single submitter
2073588	NM_052989.3(IFT122):c.3553C>T (p.Arg1185Ter)	IFT122	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2094522	NM_052989.3(IFT122):c.3563del (p.Pro1188fs)	IFT122	Pathogenic	criteria provided, single submitter
2098042	NM_052989.3(IFT122):c.356G>A (p.Trp119Ter)	IFT122	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2156861	NM_052989.3(IFT122):c.1198C>T (p.Arg400Ter)	IFT122	Pathogenic	criteria provided, single submitter
2203430	NM_052989.3(IFT122):c.3076_3080delinsGTA (p.Tyr1026fs)	IFT122	Pathogenic	criteria provided, single submitter
2693250	NM_052989.3(IFT122):c.2705_2706del (p.Thr902fs)	IFT122	Pathogenic	criteria provided, single submitter
2757396	NM_052989.3(IFT122):c.273-257C>A	IFT122	Pathogenic	criteria provided, single submitter
2770134	NM_052989.3(IFT122):c.443_449dup (p.Met151fs)	IFT122	Pathogenic	criteria provided, single submitter
2800797	NM_052989.3(IFT122):c.3575G>A (p.Trp1192Ter)	IFT122	Pathogenic	criteria provided, single submitter
2818768	NM_052989.3(IFT122):c.982C>T (p.Gln328Ter)	IFT122	Pathogenic	criteria provided, single submitter
2879426	NM_052989.3(IFT122):c.1963del (p.Glu655fs)	IFT122	Pathogenic	criteria provided, multiple submitters, no conflicts
2913590	NM_052989.3(IFT122):c.1141C>T (p.Gln381Ter)	IFT122	Pathogenic	criteria provided, single submitter
2916552	NM_052989.3(IFT122):c.916_917del (p.Leu306fs)	IFT122	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3343101	NM_052989.3(IFT122):c.3265+1G>A	IFT122	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3588403	NM_052989.3(IFT122):c.592_595del (p.Glu198fs)	IFT122	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
IFT122	Definitive	Autosomal recessive	cranioectodermal dysplasia 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFT122	Orphanet:1515	Cranioectodermal dysplasia
IFT122	Orphanet:93268	Short rib-polydactyly syndrome, Beemer-Langer 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
IFT122	HGNC:13556	ENSG00000163913	Q9HBG6	Intraflagellar transport protein 122 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFT122	Intraflagellar transport protein 122 homolog	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 required 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IFT122	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_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
left testis	1
right testis	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFT122	250	ubiquitous	marker	right testis, left testis, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFT122	2,519

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFT122	Q9HBG6	5

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	IFT122
Hedgehog ‘off’ state	1	178.4×	0.006	IFT122

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
embryonic heart tube left/right pattern formation	1	2808.7×	0.002	IFT122
embryonic body morphogenesis	1	2106.5×	0.002	IFT122
spinal cord dorsal/ventral patterning	1	2106.5×	0.002	IFT122
establishment of protein localization to organelle	1	1872.4×	0.002	IFT122
intraciliary retrograde transport	1	1123.5×	0.003	IFT122
intraciliary anterograde transport	1	887.0×	0.003	IFT122
embryonic heart tube development	1	766.0×	0.003	IFT122
camera-type eye morphogenesis	1	766.0×	0.003	IFT122
intraciliary transport	1	561.7×	0.003	IFT122
embryonic forelimb morphogenesis	1	495.6×	0.003	IFT122
negative regulation of smoothened signaling pathway	1	455.5×	0.003	IFT122
limb development	1	411.0×	0.003	IFT122
protein localization to cilium	1	401.2×	0.003	IFT122
non-motile cilium assembly	1	290.6×	0.004	IFT122
neural tube closure	1	187.2×	0.006	IFT122
cilium assembly	1	73.6×	0.014	IFT122
intracellular signal transduction	1	38.1×	0.026	IFT122

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
IFT122	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	IFT122

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)
IFT122	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04184531	Not specified	UNKNOWN	Sensenbrenner Clinical Study