Urofacial syndrome 2

Summary

Urofacial syndrome 2 (MONDO:0014049) is a disease caused by LRIG2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LRIG2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	urofacial syndrome 2
Mondo ID	MONDO:0014049
OMIM	615112
UMLS	C3554520
MedGen	767434
GARD	0015907
Is cancer (heuristic)	no

Also known as: LRIG2 Ochoa syndrome · Ochoa syndrome caused by mutation in LRIG2 · UFS2 · urofacial syndrome 2 · urofacial syndrome type 2

Data availability: 15 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › Ochoa syndrome › urofacial syndrome 2

Related subtypes (1): urofacial syndrome type 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

15 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 pathogenic, 4 likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
40206	NM_014813.3(LRIG2):c.1230del (p.Glu410fs)	LRIG2	Pathogenic	no assertion criteria provided
40207	NM_014813.3(LRIG2):c.2125C>T (p.Arg709Ter)	LRIG2	Pathogenic	no assertion criteria provided
40208	NM_014813.3(LRIG2):c.2088del (p.Ser697fs)	LRIG2	Pathogenic	no assertion criteria provided
40209	NM_014813.2(LRIG2):c.1980_1981insJX891452.1:g.1_371 (p.Ile662Phefs)	LRIG2	Pathogenic	no assertion criteria provided
4845798	NM_014813.3(LRIG2):c.2530+1G>T	LRIG2	Likely pathogenic	criteria provided, single submitter
4845891	NM_014813.3(LRIG2):c.2777_2795del (p.Glu926fs)	LRIG2	Likely pathogenic	criteria provided, single submitter
4849332	NM_014813.3(LRIG2):c.524_527del (p.Ser175fs)	LRIG2	Likely pathogenic	criteria provided, single submitter
666570	NM_014813.1(LRIG2):c.1799-2_1799-1delAG	LRIG2	Likely pathogenic	criteria provided, single submitter
3574390	NM_014813.3(LRIG2):c.31G>T (p.Glu11Ter)	LRIG2	Uncertain significance	criteria provided, single submitter
3574406	NM_014813.3(LRIG2):c.515+14A>G	LRIG2	Uncertain significance	criteria provided, single submitter
3574445	NM_014813.3(LRIG2):c.2543T>C (p.Leu848Pro)	LRIG2	Uncertain significance	criteria provided, single submitter
548630	NM_014813.3(LRIG2):c.1696C>T (p.His566Tyr)	LRIG2	Uncertain significance	criteria provided, single submitter
548631	NM_014813.3(LRIG2):c.256C>T (p.Arg86Trp)	LRIG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1300109	NM_014813.3(LRIG2):c.2124A>C (p.Thr708=)	LRIG2	Benign	criteria provided, multiple submitters, no conflicts
1300110	NM_014813.3(LRIG2):c.2531-22G>A	LRIG2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
LRIG2	Strong	Autosomal recessive	urofacial syndrome 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRIG2	Orphanet:2704	Urofacial syndrome

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
LRIG2	HGNC:20889	ENSG00000198799	O94898	Leucine-rich repeats and immunoglobulin-like domains protein 2	gencc,clinvar

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LRIG2	Antibody/Immunoglobulin	yes		Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp

Expression context

Cohort genes with no expression data: 0.

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
Brodmann (1909) area 23	1
endothelial cell	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRIG2	267	ubiquitous	yes	tendon of biceps brachii, endothelial cell, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LRIG2	1,693

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LRIG2	O94898	74.87

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
regulation of platelet-derived growth factor receptor signaling pathway	1	8426.0×	0.001	LRIG2
negative regulation of membrane protein ectodomain proteolysis	1	1872.4×	0.002	LRIG2
negative regulation of axon regeneration	1	1532.0×	0.002	LRIG2
innervation	1	887.0×	0.002	LRIG2
positive regulation of protein localization to cell surface	1	766.0×	0.002	LRIG2
membrane protein ectodomain proteolysis	1	648.1×	0.002	LRIG2
regulation of neuron migration	1	624.1×	0.002	LRIG2
protein localization to cell surface	1	495.6×	0.002	LRIG2
sensory perception of sound	1	100.9×	0.010	LRIG2

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
LRIG2	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	1	LRIG2
E	Difficult family or no structure, no drug	0

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)
LRIG2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.