Craniofacial microsomia 2

Summary

Craniofacial microsomia 2 (MONDO:0958194) is a disease caused by FOXI3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FOXI3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	craniofacial microsomia 2
Mondo ID	MONDO:0958194
OMIM	620444
UMLS	C5781610
MedGen	1830923
GARD	0026968
Is cancer (heuristic)	no

Data availability: 6 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › craniofacial microsomia › craniofacial microsomia 2

Related subtypes (1): craniofacial microsomia 1

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

6 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 2 likely pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2431349	NM_001135649.3(FOXI3):c.700T>G (p.Phe234Val)	FOXI3	Pathogenic/Likely pathogenic	no assertion criteria provided
2431350	NM_001135649.3(FOXI3):c.702C>A (p.Phe234Leu)	FOXI3	Pathogenic/Likely pathogenic	no assertion criteria provided
2431343	NM_001135649.3(FOXI3):c.706C>T (p.Arg236Trp)	FOXI3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3075660	NM_001135649.3(FOXI3):c.596T>G (p.Leu199Arg)	FOXI3	Likely pathogenic	criteria provided, single submitter
2431340	NM_001135649.3(FOXI3):c.718C>T (p.Arg240Cys)	FOXI3	Uncertain significance	criteria provided, single submitter
3902017	NM_001135649.3(FOXI3):c.1143del (p.Tyr382fs)	FOXI3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
FOXI3	Strong	Autosomal dominant	craniofacial microsomia 2	4

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
FOXI3	HGNC:35123	ENSG00000214336	A8MTJ6	Forkhead box protein I3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FOXI3	Forkhead box protein I3	Transcription factor required for pharyngeal arch development, which is involved in hair, ear, jaw and dental development.

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)
FOXI3	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2

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)	1
broad (>20)	0
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
placenta	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FOXI3	13	broad	marker	primordial germ cell in gonad, placenta, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FOXI3	876

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FOXI3	A8MTJ6	59.00

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
otic placode development	1	8426.0×	0.001	FOXI3
epidermal cell fate specification	1	3370.4×	0.001	FOXI3
parathyroid gland development	1	2407.4×	0.001	FOXI3
pharyngeal system development	1	802.5×	0.003	FOXI3
hair follicle development	1	383.0×	0.005	FOXI3
thymus development	1	337.0×	0.005	FOXI3
odontogenesis of dentin-containing tooth	1	300.9×	0.005	FOXI3
anatomical structure morphogenesis	1	139.3×	0.009	FOXI3
cell differentiation	1	29.1×	0.038	FOXI3
regulation of transcription by RNA polymerase II	1	11.7×	0.086	FOXI3

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
FOXI3	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	FOXI3

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)
FOXI3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.