Bifid uvula

Summary

Bifid uvula (MONDO:0008637) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 4

Clinical features

Signs & symptoms

Clinical features (HPO)

4 HPO clinical features (Orphanet curated; top 4 by frequency):

HPO ID	Term	Frequency
HP:0000193	Bifid uvula	Obligate (100%)
HP:0008376	Nasal, dysarthic speech	Frequent (30-79%)
HP:0011819	Submucous cleft soft palate	Occasional (5-29%)
HP:0410030	Cleft lip	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	bifid uvula
Mondo ID	MONDO:0008637
OMIM	192100
Orphanet	99771
ICD-11	684398038
SNOMED CT	18910001
UMLS	C4551488
MedGen	1646931
GARD	0019687
Is cancer (heuristic)	no

Also known as: bifidity of the uvula · uvular cleft

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › orofacial cleft › cleft palate › bifid uvula

Related subtypes (8): isolated cleft palate, cleft soft palate, Rapp-Hodgkin syndrome, cleft palate with or without ankyloglossia, X-linked, cleft hard palate, submucosal cleft palate, Kuster syndrome, soft and hard cleft palate

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1697212	NM_001659.3(ARF3):c.277G>A (p.Asp93Asn)	ARF3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARF3	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability

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
ARF3	HGNC:654	ENSG00000134287	P61204	ADP-ribosylation factor 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARF3	ADP-ribosylation factor 3	GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase.

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)
ARF3	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, Small_GTPase_ARF

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
entorhinal cortex	1
postcentral gyrus	1
prefrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARF3	300	ubiquitous	marker	prefrontal cortex, entorhinal cortex, postcentral gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARF3	232

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ARF3	P61204	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Synthesis of PIPs at the Golgi membrane	1	634.4×	0.017	ARF3
PI Metabolism	1	356.9×	0.017	ARF3
Phospholipid metabolism	1	200.3×	0.017	ARF3
ER to Golgi Anterograde Transport	1	132.8×	0.017	ARF3
Golgi-to-ER retrograde transport	1	132.8×	0.017	ARF3
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.017	ARF3
COPI-mediated anterograde transport	1	109.8×	0.017	ARF3
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.017	ARF3
Transport to the Golgi and subsequent modification	1	102.9×	0.017	ARF3
Asparagine N-linked glycosylation	1	60.1×	0.027	ARF3
Membrane Trafficking	1	37.1×	0.038	ARF3
Vesicle-mediated transport	1	34.8×	0.038	ARF3
Metabolism of lipids	1	31.6×	0.039	ARF3
Post-translational protein modification	1	19.2×	0.060	ARF3
Metabolism of proteins	1	12.4×	0.086	ARF3
Metabolism	1	11.6×	0.086	ARF3

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
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	337.0×	0.009	ARF3
vesicle-mediated transport	1	96.3×	0.015	ARF3
intracellular protein transport	1	64.8×	0.015	ARF3

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
ARF3	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	ARF3

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)
ARF3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.