Cataract 15 multiple types

Summary

Cataract 15 multiple types (MONDO:0014110) is a disease caused by MIP (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: MIP (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 68

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 15 multiple types
Mondo ID	MONDO:0014110
OMIM	615274
DOID	DOID:0110251
UMLS	C3809001
MedGen	815331
GARD	0024971
Is cancer (heuristic)	no

Also known as: cataract 15, multiple types · CTRCT15 · early-onset non-syndromic cataract caused by mutation in MIP · MIP early-onset non-syndromic cataract

Data availability: 68 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › lens disorder › cataract › early-onset non-syndromic cataract › cataract 15 multiple types

Related subtypes (28): cataract 32 multiple types, cataract 8 multiple types, cataract 42, cataract 20 multiple types, cataract 6 multiple types, cataract 13 with adult I phenotype, cataract 5 multiple types, cataract 46 juvenile-onset, cataract 40, cataract 10 multiple types, cataract 14 multiple types, pulverulent cataract, cataract 31 multiple types, cataract 26 multiple types, cataract 22 multiple types, cataract 21 multiple types, cataract 23, cataract 11 multiple types, cataract 33, cataract 17 multiple types, cataract 38, cataract 39 multiple types, cataract 19 multiple types, cataract 43, cataract 44, cataract 45, early-onset partial cataract, total early-onset cataract

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

68 retrieved; paginated sample, class counts are floors:

30 uncertain significance, 13 benign, 11 pathogenic, 7 likely benign, 3 likely pathogenic, 3 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069403	NM_012064.4(MIP):c.606+1G>C	MIP	Pathogenic	criteria provided, single submitter
14354	NM_012064.4(MIP):c.413C>G (p.Thr138Arg)	MIP	Pathogenic	no assertion criteria provided
14355	NM_012064.4(MIP):c.401A>G (p.Glu134Gly)	MIP	Pathogenic	no assertion criteria provided
1806189	NM_012064.4(MIP):c.616_632del (p.Val206fs)	MIP	Pathogenic	criteria provided, single submitter
217342	NM_012064.4(MIP):c.97C>T (p.Arg33Cys)	MIP	Pathogenic	criteria provided, multiple submitters, no conflicts
2722298	NM_012064.4(MIP):c.606+1G>T	MIP	Pathogenic	criteria provided, single submitter
377392	NM_012064.4(MIP):c.508dup (p.Leu170fs)	MIP	Pathogenic	no assertion criteria provided
4727827	NM_012064.4(MIP):c.162dup (p.Leu55fs)	MIP	Pathogenic	criteria provided, single submitter
4734471	NM_012064.4(MIP):c.530_531del (p.Tyr177fs)	MIP	Pathogenic	criteria provided, single submitter
474241	NM_012064.4(MIP):c.623del (p.Pro208fs)	MIP	Pathogenic	criteria provided, single submitter
50960	NM_012064.4(MIP):c.638del (p.Gly213fs)	MIP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
992878	NM_012064.4(MIP):c.615G>A (p.Trp205Ter)	MIP	Pathogenic	criteria provided, multiple submitters, no conflicts
1703071	NM_012064.4(MIP):c.559del (p.Arg187fs)	MIP	Likely pathogenic	criteria provided, single submitter
3061915	NM_012064.4(MIP):c.493_494insT (p.Gly165fs)	MIP	Likely pathogenic	criteria provided, single submitter
944316	NM_012064.4(MIP):c.525+1G>A	MIP	Likely pathogenic	criteria provided, single submitter
1012009	NM_012064.4(MIP):c.433A>C (p.Ile145Leu)	MIP	Uncertain significance	criteria provided, single submitter
1469523	NM_012064.4(MIP):c.119A>G (p.His40Arg)	MIP	Uncertain significance	criteria provided, single submitter
1695911	NM_012064.4(MIP):c.694G>C (p.Glu232Gln)	MIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
1992634	NM_012064.4(MIP):c.172T>G (p.Ser58Ala)	MIP	Uncertain significance	criteria provided, single submitter
2915608	NM_012064.4(MIP):c.458G>A (p.Arg153Gln)	MIP	Uncertain significance	criteria provided, single submitter
309867	NM_012064.4(MIP):c.*1103C>T	MIP	Uncertain significance	criteria provided, single submitter
309872	NM_012064.4(MIP):c.*674G>A	MIP	Uncertain significance	criteria provided, single submitter
309874	NM_012064.4(MIP):c.*601G>A	MIP	Uncertain significance	criteria provided, single submitter
309878	NM_012064.4(MIP):c.*342C>T	MIP	Uncertain significance	criteria provided, single submitter
309884	NM_012064.4(MIP):c.493G>A (p.Gly165Ser)	MIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
309886	NM_012064.4(MIP):c.361-10C>T	MIP	Uncertain significance	criteria provided, single submitter
3642157	NM_012064.4(MIP):c.569C>T (p.Ala190Val)	MIP	Uncertain significance	criteria provided, single submitter
3777139	NM_012064.4(MIP):c.652C>G (p.Leu218Val)	MIP	Uncertain significance	criteria provided, single submitter
474238	NM_012064.4(MIP):c.323C>T (p.Thr108Ile)	MIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
474240	NM_012064.4(MIP):c.560G>T (p.Arg187Leu)	MIP	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 21 · Orphanet: 8 · 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
MIP	Definitive	Autosomal dominant	cataract 15 multiple types	10
TNPO1	Definitive	Autosomal dominant	cataract 15 multiple types	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MIP	Orphanet:441452	Early-onset lamellar cataract
MIP	Orphanet:98985	Early-onset sutural cataract
MIP	Orphanet:98989	Cerulean cataract
MIP	Orphanet:98991	Early-onset nuclear cataract
MIP	Orphanet:98993	Early-onset posterior polar cataract
MIP	Orphanet:98994	Total early-onset cataract
SDR9C7	Orphanet:313	Lamellar ichthyosis
SDR9C7	Orphanet:79394	Congenital ichthyosiform erythroderma

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TNPO1	HGNC:6401	ENSG00000083312	Q92973	Transportin-1	gencc,clinvar
MIP	HGNC:7103	ENSG00000135517	P30301	Lens fiber major intrinsic protein	gencc,clinvar
SDR9C7	HGNC:29958	ENSG00000170426	Q8NEX9	Short-chain dehydrogenase/reductase family 9C member 7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNPO1	Transportin-1	Functions in nuclear protein import as nuclear transport receptor.
MIP	Lens fiber major intrinsic protein	Aquaporins form homotetrameric transmembrane channels, with each monomer independently mediating water transport across the plasma membrane along its osmotic gradient.
SDR9C7	Short-chain dehydrogenase/reductase family 9C member 7	Plays a crucial role in the formation of the epidermal permeability barrier.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNPO1	Other/Unknown	no		Importin-beta_N, ARM-like, ARM-type_fold
MIP	Other/Unknown	no		MIP, MIP_CS, Aquaporin-like
SDR9C7	Other/Unknown	no		SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
caput epididymis	1
cauda epididymis	1
corpus epididymis	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
right lobe of liver	1
skin of abdomen	1
skin of leg	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNPO1	295	ubiquitous	marker	corpus epididymis, caput epididymis, cauda epididymis
MIP	91	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right lobe of liver
SDR9C7	113	tissue_specific	yes	skin of leg, skin of abdomen, zone of skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNPO1	3,147
MIP	2,496
SDR9C7	785

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNPO1	Q92973	21

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SDR9C7	Q8NEX9	93.41
MIP	P30301	91.08

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Passive transport by Aquaporins	1	292.8×	0.011	MIP
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	1	211.5×	0.011	TNPO1
The canonical retinoid cycle in rods (twilight vision)	1	173.0×	0.011	SDR9C7
Postmitotic nuclear pore complex (NPC) reformation	1	135.9×	0.011	TNPO1
Aquaporin-mediated transport	1	122.8×	0.011	MIP
Intraflagellar transport	1	66.8×	0.017	TNPO1
Transport of small molecules	1	8.4×	0.115	MIP

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
gap junction-mediated intercellular transport	1	936.2×	0.005	MIP
maintenance of lens transparency	1	702.2×	0.005	MIP
homotypic cell-cell adhesion	1	561.7×	0.005	MIP
water transport	1	330.4×	0.007	MIP
retinol metabolic process	1	165.2×	0.011	SDR9C7
lens development in camera-type eye	1	124.8×	0.011	MIP
steroid metabolic process	1	112.3×	0.011	SDR9C7
protein import into nucleus	1	48.0×	0.023	TNPO1
visual perception	1	26.5×	0.037	MIP

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TNPO1	0	0
MIP	0	0
SDR9C7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TNPO1	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	TNPO1, MIP, SDR9C7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TNPO1	7	—
MIP	0	—
SDR9C7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.