Microphthalmia, isolated, with coloboma 7

Summary

Microphthalmia, isolated, with coloboma 7 (MONDO:0013783) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microphthalmia, isolated, with coloboma 7
Mondo ID	MONDO:0013783
OMIM	614497
UMLS	C3281027
MedGen	482657
GARD	0015811
Is cancer (heuristic)	no

Also known as: ABCB6 microphthalmia, isolated, with coloboma · MCOPCB7 · microphthalmia, isolated, with coloboma 7 · microphthalmia, isolated, with coloboma caused by mutation in ABCB6 · microphthalmia, isolated, with coloboma type 7

Data availability: 15 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 › isolated microphthalmia › microphthalmia, isolated, with coloboma › microphthalmia, isolated, with coloboma 7

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 9, 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

15 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 3 conflicting classifications of pathogenicity, 2 likely pathogenic, 1 pathogenic, 1 likely benign, 1 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
30482	NM_005689.4(ABCB6):c.2431C>G (p.Leu811Val)	ABCB6	Pathogenic	no assertion criteria provided
218180	NM_005689.4(ABCB6):c.1123C>T (p.Arg375Trp)	ABCB6	Likely pathogenic	criteria provided, single submitter
4086262	NM_005689.4(ABCB6):c.1348C>T (p.Arg450Trp)	ABCB6	Likely pathogenic	no assertion criteria provided
1283915	NM_005689.4(ABCB6):c.1511T>C (p.Val504Ala)	ABCB6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
68473	NM_005689.4(ABCB6):c.575G>A (p.Arg192Gln)	ABCB6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
771341	NM_005689.4(ABCB6):c.1361T>C (p.Val454Ala)	ABCB6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30483	NM_005689.4(ABCB6):c.169G>A (p.Ala57Thr)	ABCB6	Uncertain significance	criteria provided, multiple submitters, no conflicts
3585678	NM_005689.4(ABCB6):c.2359A>G (p.Thr787Ala)	ABCB6	Uncertain significance	criteria provided, single submitter
3585679	NM_005689.4(ABCB6):c.1864-4A>G	ABCB6	Uncertain significance	criteria provided, single submitter
3778757	NM_005689.4(ABCB6):c.89C>T (p.Thr30Met)	ABCB6	Uncertain significance	criteria provided, single submitter
916022	NM_005689.4(ABCB6):c.2000G>C (p.Gly667Ala)	ABCB6	Uncertain significance	no assertion criteria provided
993667	NM_005689.4(ABCB6):c.2215C>T (p.Arg739Cys)	ABCB6	Uncertain significance	criteria provided, multiple submitters, no conflicts
3338261	NM_005689.4(ABCB6):c.683G>T (p.Ser228Ile)	ABCB6	Likely benign	criteria provided, single submitter
3338265	NM_005689.4(ABCB6):c.316T>C (p.Tyr106His)	ABCB6	Benign	criteria provided, single submitter
783355	NM_005689.4(ABCB6):c.688-9C>T	ABCB6	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 9 · 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
ABCB6	Supportive	Autosomal dominant	microphthalmia, isolated, with coloboma	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCB6	Orphanet:241	Dyschromatosis universalis hereditaria
ABCB6	Orphanet:90044	Familial pseudohyperkalemia
ABCB6	Orphanet:98938	Colobomatous microphthalmia
ABCB6	Orphanet:98942	Coloboma of choroid and retina
ABCB6	Orphanet:98943	Coloboma of eye lens
ABCB6	Orphanet:98944	Coloboma of iris
ABCB6	Orphanet:98945	Coloboma of macula
ABCB6	Orphanet:98946	Coloboma of eyelid
ABCB6	Orphanet:98947	Coloboma of optic disc

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
ABCB6	HGNC:47	ENSG00000115657	Q9NP58	ATP-binding cassette sub-family B member 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCB6	ATP-binding cassette sub-family B member 6	ATP-dependent transporter that catalyzes the transport of a broad-spectrum of porphyrins from the cytoplasm to the extracellular space through the plasma membrane or into the vesicle lumen.

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCB6	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom

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
left ovary	1
right hemisphere of cerebellum	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCB6	140	ubiquitous	marker	right ovary, right hemisphere of cerebellum, left ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCB6	1,480

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCB6	Q9NP58	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Defective ABCB6 causes MCOPCB7	1	11420.0×	6e-04	ABCB6
Mitochondrial ABC transporters	1	2855.0×	0.001	ABCB6
ABC transporter disorders	1	439.2×	0.005	ABCB6
Disorders of transmembrane transporters	1	139.3×	0.012	ABCB6
ABC-family protein mediated transport	1	121.5×	0.012	ABCB6
Transport of small molecules	1	25.1×	0.046	ABCB6
Disease	1	13.1×	0.076	ABCB6

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
tetrapyrrole metabolic process	1	16852.0×	5e-04	ABCB6
heme transmembrane transport	1	8426.0×	5e-04	ABCB6
cellular detoxification of cadmium ion	1	5617.3×	5e-04	ABCB6
porphyrin-containing compound metabolic process	1	4213.0×	5e-04	ABCB6
porphyrin-containing compound biosynthetic process	1	4213.0×	5e-04	ABCB6
heme transport	1	4213.0×	5e-04	ABCB6
heme metabolic process	1	3370.4×	6e-04	ABCB6
intracellular copper ion homeostasis	1	936.2×	0.002	ABCB6
melanosome assembly	1	887.0×	0.002	ABCB6
skin development	1	443.5×	0.003	ABCB6
intracellular iron ion homeostasis	1	244.2×	0.005	ABCB6
transmembrane transport	1	168.5×	0.006	ABCB6
brain development	1	79.5×	0.013	ABCB6

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCB6	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
ABCB6	3	Functional:3

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	1	ABCB6
D	Druggable family + AlphaFold only, no drug	0
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)
ABCB6	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.