Orofacial cleft 10

Summary

Orofacial cleft 10 (MONDO:0013378) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 25

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	orofacial cleft 10
Mondo ID	MONDO:0013378
MeSH	C566605
OMIM	613705
DOID	DOID:0080403
UMLS	C1866070
MedGen	355621
GARD	0018306
Is cancer (heuristic)	no

Also known as: OFC10 · orofacial cleft 10 · orofacial cleft 10, isolated cases · orofacial cleft caused by mutation in SUMO1 · orofacial cleft type 10 · SUMO1 orofacial cleft

Data availability: 25 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 › orofacial cleft › cleft lip/palate › orofacial cleft 10

Related subtypes (3): orofacial cleft 11, orofacial cleft 5, orofacial cleft 15

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

25 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 6 benign, 2 likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
7629	46,XX,t(2;8)(q33.1;q24.3)	SUMO1	Pathogenic	no assertion criteria provided
559487	NM_006147.4(IRF6):c.273A>T (p.Arg91Ser)	IRF6	Uncertain significance	no assertion criteria provided
559492	NM_006147.4(IRF6):c.514C>T (p.Pro172Ser)	IRF6	Uncertain significance	no assertion criteria provided
559493	NM_006147.4(IRF6):c.595G>A (p.Glu199Lys)	IRF6	Uncertain significance	no assertion criteria provided
559496	NM_006147.4(IRF6):c.1175T>G (p.Val392Gly)	IRF6	Uncertain significance	no assertion criteria provided
333609	NM_003352.8(SUMO1):c.*944G>C	SUMO1	Uncertain significance	criteria provided, single submitter
333610	NM_003352.8(SUMO1):c.*884A>G	SUMO1	Uncertain significance	criteria provided, single submitter
333611	NM_003352.8(SUMO1):c.*724A>G	SUMO1	Uncertain significance	criteria provided, single submitter
333612	NM_003352.8(SUMO1):c.*545G>T	SUMO1	Uncertain significance	criteria provided, single submitter
333613	NM_003352.8(SUMO1):c.*475A>G	SUMO1	Uncertain significance	criteria provided, single submitter
895351	NM_003352.8(SUMO1):c.*814G>A	SUMO1	Uncertain significance	criteria provided, single submitter
895352	NM_003352.8(SUMO1):c.*776A>T	SUMO1	Uncertain significance	criteria provided, single submitter
895353	NM_003352.8(SUMO1):c.*753C>G	SUMO1	Uncertain significance	criteria provided, single submitter
895354	NM_003352.8(SUMO1):c.88-8C>T	SUMO1	Uncertain significance	criteria provided, single submitter
896763	NM_003352.8(SUMO1):c.-48C>T	SUMO1	Uncertain significance	criteria provided, single submitter
896764	NM_003352.8(SUMO1):c.-83A>G	SUMO1	Uncertain significance	criteria provided, single submitter
898330	NM_003352.8(SUMO1):c.*1038C>T	SUMO1	Uncertain significance	criteria provided, single submitter
559488	NM_006147.4(IRF6):c.362G>T (p.Gly121Val)	IRF6	Benign	no assertion criteria provided
559489	NM_006147.4(IRF6):c.443A>G (p.Asp148Gly)	IRF6	Benign	no assertion criteria provided
559490	NM_006147.4(IRF6):c.457T>G (p.Ser153Ala)	IRF6	Benign	no assertion criteria provided
559491	NM_006147.4(IRF6):c.490C>G (p.Pro164Ala)	IRF6	Benign	no assertion criteria provided
559494	NM_006147.4(IRF6):c.635G>A (p.Ser212Asn)	IRF6	Benign	no assertion criteria provided
559495	NM_006147.4(IRF6):c.1173G>T (p.Leu391Phe)	IRF6	Benign	no assertion criteria provided
333615	NM_003352.8(SUMO1):c.-32T>G	SUMO1	Likely benign	criteria provided, multiple submitters, no conflicts
896765	NM_003352.8(SUMO1):c.-94G>A	SUMO1	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 8 · 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
SUMO1	Limited	Unknown	orofacial cleft 10	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SUMO1	Orphanet:99798	Oligodontia
IRF6	Orphanet:1300	Autosomal dominant popliteal pterygium syndrome
IRF6	Orphanet:141291	Cleft lip and alveolus
IRF6	Orphanet:199302	Isolated cleft lip
IRF6	Orphanet:199306	Cleft lip/palate
IRF6	Orphanet:708014	Ectodermal dysplasia-natal teeth-skin abscesses-plantar hyperkeratosis-hearing impairment
IRF6	Orphanet:888	Van der Woude syndrome
IRF6	Orphanet:99798	Oligodontia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SUMO1	HGNC:12502	ENSG00000116030	P63165	Small ubiquitin-related modifier 1	gencc,clinvar
IRF6	HGNC:6121	ENSG00000117595	O14896	Interferon regulatory factor 6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SUMO1	Small ubiquitin-related modifier 1	Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer.
IRF6	Interferon regulatory factor 6	Probable DNA-binding transcriptional activator.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SUMO1	Other/Unknown	no		Ubiquitin-like_dom, Rad60/SUMO-like_dom, Ubiquitin-like_domsf
IRF6	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
ganglionic eminence	1
ventricular zone	1
esophagus squamous epithelium	1
secondary oocyte	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SUMO1	266	ubiquitous	marker	ganglionic eminence, cortical plate, ventricular zone
IRF6	228	broad	marker	secondary oocyte, upper leg skin, esophagus squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IRF6	1,897
SUMO1	981

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SUMO1	P63165	68

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IRF6	O14896	74.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 63. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interferon gamma signaling	2	125.5×	0.002	SUMO1, IRF6
Interferon Signaling	2	120.2×	0.002	SUMO1, IRF6
SUMOylation of nuclear envelope proteins	1	1903.3×	0.009	SUMO1
Cytokine Signaling in Immune system	2	40.8×	0.009	SUMO1, IRF6
SUMO is conjugated to E1 (UBA2:SAE1)	1	1142.0×	0.011	SUMO1
SUMO is proteolytically processed	1	951.7×	0.011	SUMO1
SUMO is transferred from E1 to E2 (UBE2I, UBC9)	1	815.7×	0.011	SUMO1
Processing and activation of SUMO	1	634.4×	0.012	SUMO1
Negative regulation of activity of TFAP2 (AP-2) family transcription factors	1	571.0×	0.012	SUMO1
Maturation of nucleoprotein	1	519.1×	0.012	SUMO1
SUMOylation of immune response proteins	1	475.8×	0.012	SUMO1
Translation of Structural Proteins	1	439.2×	0.012	SUMO1
Regulation of IFNG signaling	1	407.9×	0.012	SUMO1
Maturation of nucleoprotein	1	380.7×	0.012	SUMO1
SUMOylation of DNA methylation proteins	1	335.9×	0.012	SUMO1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	317.2×	0.012	SUMO1
SUMOylation of transcription factors	1	285.5×	0.013	SUMO1
DNA Double Strand Break Response	1	237.9×	0.015	SUMO1
Global Genome Nucleotide Excision Repair (GG-NER)	1	228.4×	0.015	SUMO1
Postmitotic nuclear pore complex (NPC) reformation	1	203.9×	0.015	SUMO1
Translation of Structural Proteins	1	203.9×	0.015	SUMO1
SUMOylation of intracellular receptors	1	167.9×	0.016	SUMO1
SUMOylation of SUMOylation proteins	1	163.1×	0.016	SUMO1
Nuclear Envelope (NE) Reassembly	1	146.4×	0.016	SUMO1
SUMOylation of ubiquitinylation proteins	1	146.4×	0.016	SUMO1
Late SARS-CoV-2 Infection Events	1	146.4×	0.016	SUMO1
Nucleotide Excision Repair	1	142.8×	0.016	SUMO1
Immune System	2	13.0×	0.016	SUMO1, IRF6
Formation of Incision Complex in GG-NER	1	126.9×	0.016	SUMO1
SUMOylation of DNA replication proteins	1	124.1×	0.016	SUMO1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
roof of mouth development	2	247.8×	5e-04	SUMO1, IRF6
protein localization to nuclear pore	1	2808.7×	0.005	SUMO1
negative regulation of action potential	1	2106.5×	0.005	SUMO1
negative regulation of transcription initiation by RNA polymerase II	1	1685.2×	0.005	SUMO1
PML body organization	1	1404.3×	0.005	SUMO1
regulation of calcium ion transmembrane transport	1	1053.2×	0.005	SUMO1
mammary gland epithelial cell differentiation	1	601.9×	0.006	IRF6
regulation of cardiac muscle cell contraction	1	561.7×	0.006	SUMO1
negative regulation of protein import into nucleus	1	468.1×	0.006	SUMO1
cranial skeletal system development	1	468.1×	0.006	IRF6
cell development	1	443.5×	0.006	IRF6
negative regulation of stem cell proliferation	1	421.3×	0.006	IRF6
cellular response to cadmium ion	1	383.0×	0.006	SUMO1
negative regulation of keratinocyte proliferation	1	351.1×	0.007	IRF6
keratinocyte proliferation	1	290.6×	0.007	IRF6
limb development	1	205.5×	0.010	IRF6
immune system process	1	195.9×	0.010	IRF6
cellular response to heat	1	172.0×	0.010	SUMO1
positive regulation of protein-containing complex assembly	1	168.5×	0.010	SUMO1
protein sumoylation	1	162.0×	0.010	SUMO1
stem cell proliferation	1	156.0×	0.010	IRF6
keratinocyte differentiation	1	123.9×	0.012	IRF6
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	1	105.3×	0.013	SUMO1
regulation of protein stability	1	62.9×	0.021	SUMO1
protein stabilization	1	33.4×	0.038	SUMO1
DNA repair	1	31.9×	0.038	SUMO1
negative regulation of cell population proliferation	1	21.1×	0.056	IRF6
negative regulation of DNA-templated transcription	1	15.8×	0.071	SUMO1
positive regulation of DNA-templated transcription	1	14.0×	0.078	IRF6
negative regulation of transcription by RNA polymerase II	1	8.9×	0.117	SUMO1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SUMO1	0	0
IRF6	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
SUMO1	13	Binding:11, Functional:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	SUMO1, IRF6

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SUMO1	13	—
IRF6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.