Orofaciodigital syndrome 17

Summary

Orofaciodigital syndrome 17 (MONDO:0033375) is a disease caused by INTU (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: INTU (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	orofaciodigital syndrome 17
Mondo ID	MONDO:0033375
OMIM	617926
DOID	DOID:0080289
UMLS	C4693640
MedGen	1644516
GARD	0025800
Is cancer (heuristic)	no

Also known as: OFD17 · OFDS XVII · oral-facial-digital syndrome, type XVII

Data availability: 11 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 › orofaciodigital syndrome › orofaciodigital syndrome 17

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 18, 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

11 retrieved; paginated sample, class counts are floors:

2 benign, 2 benign/likely benign, 2 pathogenic, 2 uncertain significance, 1 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1694472	NM_015693.4(INTU):c.2358_2359dup (p.Asn787fs)	INTU	Pathogenic	criteria provided, single submitter
3255222	NM_015693.4(INTU):c.576del (p.Lys193fs)	INTU	Pathogenic	criteria provided, single submitter
504484	NM_015693.4(INTU):c.396del (p.Asn132fs)	INTU	Pathogenic/Likely pathogenic	no assertion criteria provided
1341890	NM_015693.4(INTU):c.1305dup (p.Asn436Ter)	INTU	Likely pathogenic	criteria provided, single submitter
2713590	NM_015693.4(INTU):c.469C>T (p.Arg157Ter)	INTU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1694474	NM_015693.4(INTU):c.2527C>T (p.Arg843Cys)	INTU	Uncertain significance	criteria provided, multiple submitters, no conflicts
4082002	NM_015693.4(INTU):c.2428G>C (p.Gly810Arg)	INTU	Uncertain significance	no assertion criteria provided
1179813	NM_015693.4(INTU):c.813G>A (p.Thr271=)	INTU	Benign	criteria provided, multiple submitters, no conflicts
1249414	NM_015693.4(INTU):c.471A>G (p.Arg157=)	INTU	Benign	criteria provided, multiple submitters, no conflicts
1644449	NM_015693.4(INTU):c.683-16G>C	INTU	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
780934	NM_015693.4(INTU):c.1450-9T>G	INTU	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
INTU	Strong	Autosomal recessive	orofaciodigital syndrome 17	4

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
INTU	HGNC:29239	ENSG00000164066	Q9ULD6	Protein inturned	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
INTU	Protein inturned	Plays a key role in ciliogenesis and embryonic development.

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)
INTU	Scaffold/PPI	no		PDZ, PDZ_sf, INTU

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
right uterine tube	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
INTU	226	ubiquitous	marker	right uterine tube, bronchial epithelial cell, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
INTU	2,947

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
INTU	Q9ULD6	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Signaling by Hedgehog	1	184.2×	0.008	INTU
Hedgehog ‘off’ state	1	178.4×	0.008	INTU
Signal Transduction	1	10.2×	0.098	INTU

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
tongue morphogenesis	1	3370.4×	0.004	INTU
negative regulation of cell division	1	2407.4×	0.004	INTU
spinal cord dorsal/ventral patterning	1	2106.5×	0.004	INTU
regulation of ossification	1	1203.7×	0.004	INTU
establishment of planar polarity	1	1053.2×	0.004	INTU
negative regulation of keratinocyte proliferation	1	702.2×	0.004	INTU
regulation of smoothened signaling pathway	1	624.1×	0.004	INTU
regulation of cilium assembly	1	601.9×	0.004	INTU
motile cilium assembly	1	581.1×	0.004	INTU
intraciliary transport	1	561.7×	0.004	INTU
neural tube development	1	526.6×	0.004	INTU
hair follicle morphogenesis	1	495.6×	0.004	INTU
positive regulation of smoothened signaling pathway	1	421.3×	0.004	INTU
limb development	1	411.0×	0.004	INTU
embryonic digit morphogenesis	1	300.9×	0.005	INTU
non-motile cilium assembly	1	290.6×	0.005	INTU
keratinocyte differentiation	1	247.8×	0.005	INTU
roof of mouth development	1	247.8×	0.005	INTU
smoothened signaling pathway	1	181.2×	0.007	INTU
vesicle-mediated transport	1	96.3×	0.012	INTU
cilium assembly	1	73.6×	0.015	INTU
cell division	1	46.2×	0.022	INTU
nervous system development	1	45.9×	0.022	INTU

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
INTU	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	INTU

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)
INTU	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.