orofaciodigital syndrome V

Summary

orofaciodigital syndrome V (MONDO:0008267) is a disease caused by DDX59 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: DDX59 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12
• Phenotypes (HPO): 27

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		12	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0000161	Median cleft lip	Very frequent (80-99%)
HP:0001162	Postaxial hand polydactyly	Very frequent (80-99%)
HP:0001830	Postaxial foot polydactyly	Very frequent (80-99%)
HP:0000191	Accessory oral frenulum	Frequent (30-79%)
HP:0000288	Abnormality of the philtrum	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0010297	Bifid tongue	Frequent (30-79%)
HP:0002251	Aganglionic megacolon	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002705	High, narrow palate	Occasional (5-29%)
HP:0004736	Crossed fused renal ectopia	Occasional (5-29%)
HP:0005817	Postaxial polysyndactyly of foot	Occasional (5-29%)
HP:0006297	Enamel hypoplasia	Occasional (5-29%)
HP:0010441	Ectopic accessory finger-like appendage	Occasional (5-29%)
HP:0010800	Absent cupid’s bow	Occasional (5-29%)
HP:0011069	Supernumerary tooth	Occasional (5-29%)
HP:0012738	Agenesis of canine	Occasional (5-29%)
HP:0100335	Non-midline cleft of the upper lip	Occasional (5-29%)
HP:0000185	Cleft soft palate	Occasional (5-29%)
HP:0000190	Abnormal oral frenulum morphology	Occasional (5-29%)
HP:0000193	Bifid uvula	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000668	Hypodontia	Occasional (5-29%)
HP:0001274	Agenesis of corpus callosum	Occasional (5-29%)
HP:0001636	Tetralogy of Fallot	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	orofaciodigital syndrome V
Mondo ID	MONDO:0008267
MeSH	C557819
OMIM	174300
Orphanet	2919
DOID	DOID:0060375
SNOMED CT	722105002
UMLS	C1868118
MedGen	358131
GARD	0004120
Is cancer (heuristic)	no

Also known as: OFD syndrome 5 · OFD5 · oral facial digital syndrome 5 · oral facial digital syndrome type 5 · oral-facial-digital syndrome 5 · oral-facial-digital syndrome type 5 · orofaciodigital syndrome 5 · orofaciodigital syndrome type 5 · orofaciodigital syndrome type V · orofaciodigital syndrome V · orofaciodigital syndrome, Thurston type · polydactyly postaxial with median cleft of upper lip · Thurston syndrome

Data availability: 12 ClinVar variants · 4 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 V

Related subtypes (18): orofaciodigital syndrome X, 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 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

12 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 pathogenic, 2 benign, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1332918	NM_001031725.6(DDX59):c.1859G>T (p.Ter620Leu)	DDX59	Pathogenic	no assertion criteria provided
4689396	NC_000001.10:g.(?200613164)(200613646_200617566)del	DDX59	Pathogenic	criteria provided, single submitter
801603	NM_001031725.6(DDX59):c.185del (p.Phe62fs)	DDX59	Pathogenic	criteria provided, multiple submitters, no conflicts
88653	NM_001031725.6(DDX59):c.1100T>G (p.Val367Gly)	DDX59	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1299500	NM_001031725.6(DDX59):c.1597-6T>G	DDX59	Likely pathogenic	criteria provided, single submitter
800916	NM_001031725.6(DDX59):c.1648AAT[2] (p.Asn552del)	DDX59	Likely pathogenic	no assertion criteria provided
1033220	NM_001031725.6(DDX59):c.27C>G (p.Ile9Met)	DDX59	Uncertain significance	criteria provided, multiple submitters, no conflicts
1472009	NM_001031725.6(DDX59):c.511C>T (p.His171Tyr)	DDX59	Uncertain significance	criteria provided, multiple submitters, no conflicts
637029	NM_001031725.6(DDX59):c.751T>C (p.Ser251Pro)	DDX59	Uncertain significance	criteria provided, single submitter
88654	NM_001031725.6(DDX59):c.1600G>A (p.Gly534Arg)	DDX59	Uncertain significance	criteria provided, single submitter
1231036	NM_001031725.6(DDX59):c.1314+23A>G	DDX59	Benign	criteria provided, multiple submitters, no conflicts
1255474	NM_001031725.6(DDX59):c.1431A>G (p.Ser477=)	DDX59	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
DDX59	Strong	Autosomal recessive	orofaciodigital syndrome V	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DDX59	Orphanet:2919	Orofaciodigital syndrome type 5

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
DDX59	HGNC:25360	ENSG00000118197	Q5T1V6	Probable ATP-dependent RNA helicase DDX59	gencc,clinvar

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)
DDX59	Transcription factor	no		Helicase_C-like, Znf_HIT, DEAD/DEAH_box_helicase_dom

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
buccal mucosa cell	1
pancreatic ductal cell	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DDX59	256	ubiquitous	marker	buccal mucosa cell, pancreatic ductal cell, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DDX59	2,606

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DDX59	Q5T1V6	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DDX59	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
DDX59	1	Binding:1

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	DDX59

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)
DDX59	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.