Linear skin defects with multiple congenital anomalies 2

Summary

Linear skin defects with multiple congenital anomalies 2 (MONDO:0010474) is a disease caused by COX7B (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: COX7B (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	linear skin defects with multiple congenital anomalies 2
Mondo ID	MONDO:0010474
OMIM	300887
DOID	DOID:0111877
UMLS	C3550921
MedGen	763835
GARD	0015272
Is cancer (heuristic)	no

Also known as: COX7B microphthalmia with linear skin defects syndrome · linear skin defects with multiple congenital anomalies 2 · linear skin defects with multiple congenital anomalies 2, X-linked dominant · linear skin defects with multiple congenital anomalies type 2 · LSDMCA2 · microphthalmia with linear skin defects syndrome caused by mutation in COX7B

Data availability: 7 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic microphthalmia › linear skin defects with multiple congenital anomalies › linear skin defects with multiple congenital anomalies 2

Related subtypes (2): linear skin defects with multiple congenital anomalies 3, linear skin defects with multiple congenital anomalies 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

7 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
39767	NM_001866.3(COX7B):c.196del (p.Leu66fs)	COX7B	Pathogenic	no assertion criteria provided
39768	NM_001866.3(COX7B):c.41-2A>G	COX7B	Pathogenic	no assertion criteria provided
39769	NM_001866.2(COX7B):c.55C>T (p.Gln19Ter)	COX7B	Pathogenic	no assertion criteria provided
2782795	NM_001367916.1(MAGT1):c.49G>A (p.Ala17Thr)	LOC130068460	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029387	NM_001866.3(COX7B):c.86G>A (p.Arg29His)	COX7B	Uncertain significance	criteria provided, multiple submitters, no conflicts
4531356	NM_001866.3(COX7B):c.206T>C (p.Val69Ala)	COX7B	Uncertain significance	criteria provided, single submitter
638343	NM_001866.3(COX7B):c.217A>G (p.Thr73Ala)	COX7B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
COX7B	Definitive	X-linked	linear skin defects with multiple congenital anomalies 2	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COX7B	Orphanet:2556	Microphthalmia with linear skin defects 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
COX7B	HGNC:2291	ENSG00000131174	P24311	Cytochrome c oxidase subunit 7B, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COX7B	Cytochrome c oxidase subunit 7B, mitochondrial	Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.

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)
COX7B	Other/Unknown	no		Cyt_c_oxidase_suVIIB, Cyt_c_oxidase_suVIIB_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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
biceps brachii	1
heart right ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COX7B	295	ubiquitous	marker	heart right ventricle, apex of heart, biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COX7B	1,135

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COX7B	P24311	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Complex IV assembly	1	228.4×	0.010	COX7B
Cytoprotection by HMOX1	1	184.2×	0.010	COX7B
TP53 Regulates Metabolic Genes	1	129.8×	0.010	COX7B
Respiratory electron transport	1	95.2×	0.011	COX7B

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
mitochondrial electron transport, cytochrome c to oxygen	1	766.0×	0.003	COX7B
cellular respiration	1	432.1×	0.003	COX7B
central nervous system development	1	115.4×	0.009	COX7B

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
COX7B	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	COX7B

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)
COX7B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.