Keratoconus 9

Summary

Keratoconus 9 (MONDO:0054771) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	keratoconus 9
Mondo ID	MONDO:0054771
OMIM	617928
UMLS	C4693660
MedGen	1645093
GARD	0025972
Is cancer (heuristic)	no

Also known as: keratoconus 9 · KTCN9

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › corneal disorder › keratoconus › keratoconus 9

Related subtypes (10): acute hydrops keratoconus, keratoconus, stable condition, keratoconus 1, keratoconus 3, keratoconus 2, keratoconus 4, keratoconus 5, keratoconus 6, keratoconus 8, keratoconus 7

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

5 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
517113	NM_080386.4(TUBA3D):c.31C>T (p.Gln11Ter)	MZT2A	Pathogenic	no assertion criteria provided
517114	NM_080386.4(TUBA3D):c.200_201dup (p.Val68fs)	MZT2A	Pathogenic	no assertion criteria provided
3780771	NM_080386.4(TUBA3D):c.636dup (p.Cys213fs)	MZT2A	Uncertain significance	criteria provided, single submitter
3892795	NM_080386.4(TUBA3D):c.484G>A (p.Gly162Ser)	MZT2A	Uncertain significance	criteria provided, single submitter
3892794	NM_080386.4(TUBA3D):c.1342G>A (p.Glu448Lys)	TUBA3D	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
TUBA3D	Limited	Unknown	keratoconus 9

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TUBA3D	HGNC:24071	ENSG00000075886	P0DPH8	Tubulin alpha-3D chain	gencc,clinvar
MZT2A	HGNC:33187	ENSG00000173272	Q6P582	Mitotic-spindle organizing protein 2A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TUBA3D	Tubulin alpha-3D chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
MZT2A	Mitotic-spindle organizing protein 2A	Required for the recruitment and the assembly of the gamma-tubulin ring complex (gTuRC) at the centrosome.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TUBA3D	Other/Unknown	no		Tubulin, Alpha_tubulin, Tubulin_FtsZ_GTPase
MZT2A	Other/Unknown	no		MOZART2

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
right testis	1
testis	1
amygdala	1
apex of heart	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TUBA3D	130	tissue_specific	marker	right testis, left testis, testis
MZT2A	286	ubiquitous	marker	parotid gland, apex of heart, amygdala

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MZT2A	346
TUBA3D	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MZT2A	Q6P582	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TUBA3D	P0DPH8	91.57

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 88. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitotic G2-G2/M phases	2	126.9×	0.002	TUBA3D, MZT2A
G2/M Transition	2	126.9×	0.002	TUBA3D, MZT2A
Recruitment of NuMA to mitotic centrosomes	2	116.5×	0.002	TUBA3D, MZT2A
Mitotic Prometaphase	2	69.2×	0.004	TUBA3D, MZT2A
M Phase	2	66.0×	0.004	TUBA3D, MZT2A
Cell Cycle, Mitotic	2	48.2×	0.006	TUBA3D, MZT2A
Cell Cycle	2	36.0×	0.010	TUBA3D, MZT2A
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	271.9×	0.025	TUBA3D
Transport of connexons to the plasma membrane	1	271.9×	0.025	TUBA3D
Gap junction trafficking and regulation	1	237.9×	0.025	TUBA3D
Gap junction trafficking	1	237.9×	0.025	TUBA3D
Post-chaperonin tubulin folding pathway	1	237.9×	0.025	TUBA3D
Formation of tubulin folding intermediates by CCT/TriC	1	211.5×	0.025	TUBA3D
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1	203.9×	0.025	TUBA3D
Prefoldin mediated transfer of substrate to CCT/TriC	1	196.9×	0.025	TUBA3D
Activation of AMPK downstream of NMDARs	1	190.3×	0.025	TUBA3D
RHO GTPases activate IQGAPs	1	173.0×	0.025	TUBA3D
Sealing of the nuclear envelope (NE) by ESCRT-III	1	173.0×	0.025	TUBA3D
HCMV Infection	1	163.1×	0.025	TUBA3D
Chaperonin-mediated protein folding	1	150.3×	0.025	TUBA3D
Gap junction assembly	1	146.4×	0.025	TUBA3D
Nuclear Envelope (NE) Reassembly	1	146.4×	0.025	TUBA3D
Selective autophagy	1	139.3×	0.025	TUBA3D
Protein folding	1	129.8×	0.025	TUBA3D
Centrosome maturation	1	126.9×	0.025	MZT2A
Assembly and cell surface presentation of NMDA receptors	1	126.9×	0.025	TUBA3D
Cargo trafficking to the periciliary membrane	1	124.1×	0.025	TUBA3D
Aggrephagy	1	124.1×	0.025	TUBA3D
Carboxyterminal post-translational modifications of tubulin	1	119.0×	0.025	TUBA3D
Recycling pathway of L1	1	112.0×	0.025	TUBA3D

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
mitotic cell cycle	1	133.8×	0.008	TUBA3D
microtubule cytoskeleton organization	1	121.2×	0.008	TUBA3D

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
TUBA3D	0	0
MZT2A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	TUBA3D, MZT2A

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TUBA3D	0	—
MZT2A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.