GRHL3-related orofacial clefting

Summary

GRHL3-related orofacial clefting (MONDO:0100579) is a disease caused by GRHL3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: GRHL3 (GenCC Definitive)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	GRHL3-related orofacial clefting
Mondo ID	MONDO:0100579
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › orofacial cleft › GRHL3-related orofacial clefting

Related subtypes (15): cleft lip, orofacial cleft 1, cleft lip/palate-ectodermal dysplasia syndrome, orofacial cleft 2, orofacial cleft 4, orofacial cleft 9, orofacial cleft 12, orofacial cleft 13, familial median cleft of the upper and lower lips, cleft lip and alveolus, cleft lip/palate, cleft palate, orofacial cleft 8, orofacial cleft 7, ARHGAP29-related non-syndromic orofacial cleft

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: 6 · 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
GRHL3	Definitive	Autosomal dominant	GRHL3-related orofacial clefting	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GRHL3	Orphanet:101023	Cleft hard palate
GRHL3	Orphanet:155878	Submucosal cleft palate
GRHL3	Orphanet:888	Van der Woude syndrome
GRHL3	Orphanet:99771	Bifid uvula
GRHL3	Orphanet:99772	Cleft velum

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
GRHL3	HGNC:25839	ENSG00000158055	Q8TE85	Grainyhead-like protein 3 homolog	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GRHL3	Grainyhead-like protein 3 homolog	Transcription factor playing important roles in primary neurulation and in the differentiation of stratified epithelia of both ectodermal and endodermal origin.

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)
GRHL3	Transcription factor	no		CP2, TF_CP2-like, GRHL1/CP2_C

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
esophagus mucosa	1
gingival epithelium	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GRHL3	164	broad	marker	lower esophagus mucosa, esophagus mucosa, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GRHL3	1,270

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GRHL3	Q8TE85	61.27

Function

Pathway analysis

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

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
ectoderm development	1	1203.7×	0.005	GRHL3
establishment of planar polarity	1	1053.2×	0.005	GRHL3
eyelid development in camera-type eye	1	1053.2×	0.005	GRHL3
cochlea morphogenesis	1	581.1×	0.005	GRHL3
pattern specification process	1	468.1×	0.005	GRHL3
establishment of skin barrier	1	455.5×	0.005	GRHL3
wound healing	1	227.7×	0.009	GRHL3
epidermis development	1	210.7×	0.009	GRHL3
neural tube closure	1	187.2×	0.009	GRHL3
regulation of actin cytoskeleton organization	1	157.5×	0.010	GRHL3
central nervous system development	1	115.4×	0.012	GRHL3
transcription by RNA polymerase II	1	70.5×	0.018	GRHL3
positive regulation of gene expression	1	38.7×	0.030	GRHL3
positive regulation of transcription by RNA polymerase II	1	14.9×	0.072	GRHL3
regulation of transcription by RNA polymerase II	1	11.7×	0.086	GRHL3

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
GRHL3	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	GRHL3

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)
GRHL3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.