Microphthalmia, isolated, with coloboma 9

Summary

Microphthalmia, isolated, with coloboma 9 (MONDO:0014059) is a disease caused by TENM3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TENM3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 25

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microphthalmia, isolated, with coloboma 9
Mondo ID	MONDO:0014059
OMIM	615145
UMLS	C3554592
MedGen	767506
GARD	0015909
Is cancer (heuristic)	no

Also known as: MCOPCB9 · microphthalmia, isolated, with coloboma 9 · microphthalmia, isolated, with coloboma caused by mutation in TENM3 · microphthalmia, isolated, with coloboma type 9 · microphthalmia, syndromic 15 · TENM3 microphthalmia, isolated, with coloboma

Data availability: 25 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 › isolated microphthalmia › microphthalmia, isolated, with coloboma › microphthalmia, isolated, with coloboma 9

Related subtypes (11): microphthalmia, isolated, with coloboma 4, microphthalmia with coloboma 2, microphthalmia, isolated, with coloboma 3, microphthalmia, isolated, with coloboma 5, microphthalmia, isolated, with coloboma 6, microphthalmia, isolated, with coloboma 7, microphthalmia, isolated, with coloboma 10, microphthalmia with coloboma 1, microphthalmia, isolated, with coloboma 8, microphthalmia/coloboma 11, microphthalmia/coloboma 13

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

25 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 5 benign, 4 likely pathogenic, 3 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1699299	NM_001080477.4(TENM3):c.2279G>A (p.Trp760Ter)	TENM3	Pathogenic	criteria provided, single submitter
41420	NM_001080477.4(TENM3):c.2083dup (p.Thr695fs)	TENM3	Pathogenic	no assertion criteria provided
638054	NM_001080477.4(TENM3):c.1558C>T (p.Arg520Ter)	TENM3	Pathogenic	criteria provided, single submitter
3362545	NM_001080477.4(TENM3):c.6006_6009del (p.Gln2003fs)	TENM3	Likely pathogenic	criteria provided, single submitter
3777050	NM_001080477.4(TENM3):c.5500C>T (p.Arg1834Ter)	TENM3	Likely pathogenic	criteria provided, single submitter
487482	NM_001080477.4(TENM3):c.7687C>T (p.Arg2563Trp)	TENM3	Likely pathogenic	criteria provided, single submitter
487483	NM_001080477.4(TENM3):c.4046C>G (p.Ala1349Gly)	TENM3	Likely pathogenic	criteria provided, single submitter
2510407	NM_001080477.4(TENM3):c.1441G>A (p.Gly481Ser)	TENM3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031043	NM_001080477.4(TENM3):c.8053G>A (p.Ala2685Thr)	TENM3	Uncertain significance	criteria provided, single submitter
1031795	NM_001080477.4(TENM3):c.4925C>T (p.Thr1642Met)	TENM3	Uncertain significance	criteria provided, single submitter
1283916	NM_001080477.4(TENM3):c.1982A>G (p.Glu661Gly)	TENM3	Uncertain significance	no assertion criteria provided
1283917	NM_001080477.4(TENM3):c.4411C>T (p.Leu1471Phe)	TENM3	Uncertain significance	no assertion criteria provided
2228508	NM_001080477.4(TENM3):c.4481G>A (p.Arg1494Gln)	TENM3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2437034	NM_001080477.4(TENM3):c.7964A>G (p.Lys2655Arg)	TENM3	Uncertain significance	criteria provided, single submitter
2500694	NM_001080477.4(TENM3):c.6605C>T (p.Thr2202Met)	TENM3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2500797	NM_001080477.4(TENM3):c.4487G>A (p.Arg1496Gln)	TENM3	Uncertain significance	criteria provided, single submitter
2504947	NM_001080477.4(TENM3):c.1513G>T (p.Val505Leu)	TENM3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2665029	NM_001080477.4(TENM3):c.631A>G (p.Arg211Gly)	TENM3	Uncertain significance	criteria provided, single submitter
2665030	NM_001080477.4(TENM3):c.749+4836T>G	TENM3	Uncertain significance	criteria provided, single submitter
3780704	NM_001080477.4(TENM3):c.2144dup (p.Cys716fs)	TENM3	Uncertain significance	criteria provided, single submitter
1252757	NM_001080477.4(TENM3):c.3379+25G>C	TENM3	Benign	criteria provided, multiple submitters, no conflicts
1270987	NM_001080477.4(TENM3):c.3863-26G>C	TENM3	Benign	criteria provided, multiple submitters, no conflicts
257347	NM_001080477.4(TENM3):c.1791T>C (p.Ser597=)	TENM3	Benign	criteria provided, multiple submitters, no conflicts
257353	NM_001080477.4(TENM3):c.3957C>T (p.Gly1319=)	TENM3	Benign	criteria provided, multiple submitters, no conflicts
677188	NM_001080477.4(TENM3):c.3629+21G>A	TENM3	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
TENM3	Strong	Autosomal recessive	microphthalmia, isolated, with coloboma 9	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TENM3	Orphanet:98938	Colobomatous microphthalmia

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
TENM3	HGNC:29944	ENSG00000218336	Q9P273	Teneurin-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TENM3	Teneurin-3	Involved in neural development by regulating the establishment of proper connectivity within the nervous system.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TENM3	Scaffold/PPI	no		EGF, YD, CarboxyPept-like_regulatory

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
adrenal tissue	1
stromal cell of endometrium	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TENM3	189	ubiquitous	marker	sural nerve, adrenal tissue, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TENM3	1,704

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TENM3	Q9P273	77.76

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 homophilic cell adhesion	1	8426.0×	7e-04	TENM3
camera-type eye morphogenesis	1	766.0×	0.004	TENM3
neuron development	1	255.3×	0.008	TENM3
homophilic cell-cell adhesion	1	140.4×	0.009	TENM3
positive regulation of neuron projection development	1	137.0×	0.009	TENM3
signal transduction	1	16.1×	0.062	TENM3

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
TENM3	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	TENM3

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)
TENM3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.