Teebi hypertelorism syndrome 2

Summary

Teebi hypertelorism syndrome 2 (MONDO:0030674) is a disease caused by CDH11 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CDH11 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Teebi hypertelorism syndrome 2
Mondo ID	MONDO:0030674
OMIM	619736
DOID	DOID:0081074
UMLS	C5676911
MedGen	1809276
Is cancer (heuristic)	no

Also known as: TBHS2 · Teebi hypertelorism syndrome 2

Data availability: 10 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › Teebi hypertelorism syndrome › Teebi hypertelorism syndrome 2

Related subtypes (1): Teebi hypertelorism syndrome 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

10 retrieved; paginated sample, class counts are floors:

5 pathogenic, 3 uncertain significance, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1339266	NM_001797.4(CDH11):c.979G>T (p.Gly327Trp)	CDH11	Pathogenic	no assertion criteria provided
1339267	NM_001797.4(CDH11):c.164G>C (p.Trp55Ser)	CDH11	Pathogenic	no assertion criteria provided
1339268	NM_001797.4(CDH11):c.780T>A (p.Asp260Glu)	CDH11	Pathogenic	no assertion criteria provided
1339269	NM_001797.4(CDH11):c.778G>A (p.Asp260Asn)	CDH11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1339270	NM_001797.4(CDH11):c.1121T>A (p.Val374Glu)	CDH11	Pathogenic	no assertion criteria provided
1339271	NM_001797.4(CDH11):c.835G>C (p.Glu279Gln)	CDH11	Pathogenic	no assertion criteria provided
2500121	NM_001797.4(CDH11):c.229C>T (p.Leu77Phe)	CDH11	Likely pathogenic	no assertion criteria provided
3238652	NM_001797.4(CDH11):c.1969C>T (p.Arg657Cys)	CDH11	Uncertain significance	no assertion criteria provided
3242181	NM_001797.4(CDH11):c.2152G>A (p.Asp718Asn)	CDH11	Uncertain significance	criteria provided, multiple submitters, no conflicts
3377762	NM_001797.4(CDH11):c.1145T>C (p.Met382Thr)	CDH11	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
CDH11	Strong	Autosomal dominant	Teebi hypertelorism syndrome 2	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDH11	Orphanet:1299	Branchioskeletogenital 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
CDH11	HGNC:1750	ENSG00000140937	P55287	Cadherin-11	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDH11	Cadherin-11	Cadherins are calcium-dependent cell adhesion proteins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDH11	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf

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
periodontal ligament	1
stromal cell of endometrium	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDH11	277	ubiquitous	marker	periodontal ligament, stromal cell of endometrium, tibia

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDH11	2,302

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDH11	P55287	77.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 1 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
CDH11 homotypic and heterotypic interactions	1	1631.4×	0.003	CDH11
Regulation of CDH11 mRNA translation by microRNAs	1	1268.9×	0.003	CDH11
Regulation of CDH11 function	1	1038.2×	0.003	CDH11
Regulation of CDH11 gene transcription	1	1038.2×	0.003	CDH11
Regulation of CDH11 Expression and Function	1	815.7×	0.003	CDH11
Regulation of Homotypic Cell-Cell Adhesion	1	671.8×	0.003	CDH11
Regulation of Expression and Function of Type II Classical Cadherins	1	671.8×	0.003	CDH11
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	496.5×	0.003	CDH11
Adherens junctions interactions	1	248.3×	0.005	CDH11
Cell-cell junction organization	1	248.3×	0.005	CDH11
Cell junction organization	1	187.2×	0.006	CDH11
Activation of STAT3 by cadherin engagement	1	163.1×	0.007	CDH11
Cell-Cell communication	1	137.6×	0.007	CDH11

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
aortic valve formation	1	8426.0×	0.002	CDH11
corticospinal tract morphogenesis	1	2407.4×	0.003	CDH11
cell-substrate adhesion	1	766.0×	0.005	CDH11
focal adhesion assembly	1	526.6×	0.005	CDH11
adherens junction organization	1	510.7×	0.005	CDH11
calcium-dependent cell-cell adhesion	1	481.5×	0.005	CDH11
cell-cell junction assembly	1	443.5×	0.005	CDH11
cell-cell adhesion mediated by cadherin	1	411.0×	0.005	CDH11
ossification	1	227.7×	0.008	CDH11
modulation of chemical synaptic transmission	1	183.2×	0.009	CDH11
cell morphogenesis	1	157.5×	0.009	CDH11
homophilic cell-cell adhesion	1	140.4×	0.009	CDH11
skeletal system development	1	125.8×	0.010	CDH11
negative regulation of cell migration	1	111.6×	0.010	CDH11
cell migration	1	61.5×	0.017	CDH11
cell adhesion	1	37.5×	0.027	CDH11

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
CDH11	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	CDH11

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)
CDH11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.