Commissural facial cleft

Summary

Commissural facial cleft (MONDO:0013300) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	commissural facial cleft
Mondo ID	MONDO:0013300
MeSH	D008265
OMIM	613545
Orphanet	141276
ICD-10-CM	Q18.4
ICD-11	1460924303
SNOMED CT	40159009
UMLS	C3150792
MedGen	462142
GARD	0016975
Is cancer (heuristic)	no

Also known as: macrostomia

Data availability: 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › facial cleft › commissural facial cleft

Related subtypes (8): bifid nose, median cleft of the upper lip and maxilla, Tessier number 5 facial cleft, Tessier number 6 facial cleft, midline cervical cleft, coloboma of superior eyelid, coloboma of inferior eyelid, median cleft lip/mandibule

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 5 · 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
SPECC1L	Strong	Autosomal dominant	Tessier number 4 facial cleft	9
PTCH2	Supportive	Autosomal dominant	commissural facial cleft	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPECC1L	Orphanet:141258	Tessier number 4 facial cleft
SPECC1L	Orphanet:141276	Tessier number 7 facial cleft
SPECC1L	Orphanet:1519	SPECC1L-related hypertelorism syndrome
PTCH2	Orphanet:141276	Tessier number 7 facial cleft
PTCH2	Orphanet:377	Gorlin syndrome

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
SPECC1L	HGNC:29022	ENSG00000100014	Q69YQ0	Cytospin-A	gencc
PTCH2	HGNC:9586	ENSG00000117425	Q9Y6C5	Protein patched homolog 2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPECC1L	Cytospin-A	Involved in cytokinesis and spindle organization.
PTCH2	Protein patched homolog 2	Plays a role in the control of cellular growth.

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)
SPECC1L	Other/Unknown	no		CH_dom, CH_dom_sf, F-actin_Monoox_Mical
PTCH2	Other/Unknown	no		SSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD

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
male germ line stem cell (sensu Vertebrata) in testis	2
calcaneal tendon	1
tendon	1
left testis	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPECC1L	274	ubiquitous	marker	calcaneal tendon, tendon, male germ line stem cell (sensu Vertebrata) in testis
PTCH2	162	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, left testis, right ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPECC1L	1,695
PTCH2	1,199

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PTCH2	Q9Y6C5	79.25
SPECC1L	Q69YQ0	67.07

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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
GLI proteins bind promoters of Hh responsive genes to promote transcription	1	1631.4×	0.001	PTCH2
Class B/2 (Secretin family receptors)	1	190.3×	0.005	PTCH2

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
neural crest cell delamination	1	8426.0×	0.002	SPECC1L
anterior neural tube closure	1	2106.5×	0.003	SPECC1L
epidermal cell fate specification	1	1685.2×	0.003	PTCH2
negative regulation of actin filament depolymerization	1	1404.3×	0.003	SPECC1L
positive regulation of epidermal cell differentiation	1	1053.2×	0.003	PTCH2
cell fate determination	1	468.1×	0.005	PTCH2
hair cycle	1	468.1×	0.005	PTCH2
adherens junction organization	1	255.3×	0.007	SPECC1L
negative regulation of microtubule depolymerization	1	247.8×	0.007	SPECC1L
negative regulation of smoothened signaling pathway	1	227.7×	0.007	PTCH2
skin development	1	221.7×	0.007	PTCH2
regulation of cell growth	1	110.9×	0.013	PTCH2
actin cytoskeleton organization	1	39.6×	0.031	SPECC1L
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	39.2×	0.031	SPECC1L
cell migration	1	30.8×	0.037	SPECC1L
cell division	1	23.1×	0.046	SPECC1L
cell adhesion	1	18.7×	0.053	SPECC1L

Therapeutics

Drug target analysis

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

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
SPECC1L	1	2
PTCH2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SPECC1L

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SPECC1L	6	Binding:6

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	SPECC1L

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	1	SPECC1L
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PTCH2

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)
PTCH2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.