Orofaciodigital syndrome 18

Summary

Orofaciodigital syndrome 18 (MONDO:0054770) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	orofaciodigital syndrome 18
Mondo ID	MONDO:0054770
OMIM	617927
Orphanet	508501
DOID	DOID:0060961
UMLS	C5567903
MedGen	1799326
GARD	0022069
Is cancer (heuristic)	no

Also known as: OFD18 · Ofds 18 · oral-facial-digital syndrome type 18 · oral-facial-digital syndrome with short stature and brachymesophalangy · orofaciodigital syndrome type 18

Data availability: 5 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 › orofaciodigital syndrome › orofaciodigital syndrome 18

Related subtypes (18): orofaciodigital syndrome X, orofaciodigital syndrome V, orofaciodigital syndrome type II, orofaciodigital syndrome III, orofaciodigital syndrome IV, orofaciodigital syndrome IX, orofaciodigital syndrome type 6, orofaciodigital syndrome VIII, orofaciodigital syndrome VII, orofaciodigital syndrome XI, orofaciodigital syndrome type 14, orofaciodigital syndrome XV, orofaciodigital syndrome type 12, orofaciodigital syndrome 16, orofaciodigital syndrome 17, orofaciodigital syndrome 19, orofaciodigital syndrome 20, orofaciodigital syndrome 21

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

5 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 benign, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
506288	NM_018010.4(IFT57):c.777G>A (p.Lys259=)	IFT57	Pathogenic	no assertion criteria provided
592142	NM_018010.4(IFT57):c.585+3A>G	IFT57	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2502827	NM_018010.4(IFT57):c.463G>T (p.Ala155Ser)	IFT57	Uncertain significance	no assertion criteria provided
548601	NM_018010.4(IFT57):c.1168A>G (p.Met390Val)	IFT57	Uncertain significance	criteria provided, single submitter
1285254	NM_018010.4(IFT57):c.375+17C>G	IFT57	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · 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
IFT57	Limited	Unknown	orofaciodigital syndrome 18	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFT57	Orphanet:508501	Orofaciodigital syndrome type 18

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
IFT57	HGNC:17367	ENSG00000114446	Q9NWB7	Intraflagellar transport protein 57 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFT57	Intraflagellar transport protein 57 homolog	Required for the formation of cilia.

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)
IFT57	Other/Unknown	no		Intra-flagellar_transport_57

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
epithelium of bronchus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFT57	289	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFT57	1,623

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IFT57	Q9NWB7	76.92

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	IFT57
Hedgehog ‘off’ state	1	178.4×	0.006	IFT57

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 anterograde transport	1	887.0×	0.004	IFT57
negative regulation of keratinocyte proliferation	1	702.2×	0.004	IFT57
keratinocyte proliferation	1	581.1×	0.004	IFT57
motile cilium assembly	1	581.1×	0.004	IFT57
intraciliary transport	1	561.7×	0.004	IFT57
non-motile cilium assembly	1	290.6×	0.006	IFT57
heart looping	1	267.5×	0.006	IFT57
neural tube closure	1	187.2×	0.007	IFT57
smoothened signaling pathway	1	181.2×	0.007	IFT57
regulation of apoptotic process	1	83.4×	0.014	IFT57
cilium assembly	1	73.6×	0.015	IFT57
apoptotic process	1	28.7×	0.035	IFT57

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
IFT57	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	IFT57

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)
IFT57	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.