Linear skin defects with multiple congenital anomalies 3

Summary

Linear skin defects with multiple congenital anomalies 3 (MONDO:0010494) is a disease caused by NDUFB11 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NDUFB11 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	linear skin defects with multiple congenital anomalies 3
Mondo ID	MONDO:0010494
OMIM	300952
DOID	DOID:0111876
UMLS	C4225421
MedGen	906997
GARD	0015276
Is cancer (heuristic)	no

Also known as: linear skin defects with multiple congenital anomalies 3 · linear skin defects with multiple congenital anomalies 3, X-linked dominant · linear skin defects with multiple congenital anomalies type 3 · LSDMCA3 · microphthalmia with linear skin defects syndrome caused by mutation in NDUFB11 · NDUFB11 microphthalmia with linear skin defects syndrome

Data availability: 10 ClinVar variants · 1 GenCC gene-disease record.

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 3

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

10 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 likely pathogenic, 2 pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
190302	NM_001135998.3(NDUFB11):c.262C>T (p.Arg88Ter)	NDUFB11	Pathogenic	criteria provided, multiple submitters, no conflicts
190303	NM_001135998.3(NDUFB11):c.372del (p.Arg124fs)	NDUFB11	Pathogenic	no assertion criteria provided
2442422	NM_001135998.3(NDUFB11):c.270CTT[2] (p.Phe93del)	NDUFB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372149	NM_001135998.3(NDUFB11):c.361G>A (p.Glu121Lys)	NDUFB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2584528	NM_001135998.3(NDUFB11):c.385C>T (p.Arg129Ter)	NDUFB11	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4077077	NM_001135998.3(NDUFB11):c.338+12del	NDUFB11	Likely pathogenic	criteria provided, single submitter
4294507	NM_001135998.3(NDUFB11):c.176dup (p.Glu60fs)	NDUFB11	Likely pathogenic	criteria provided, single submitter
1048558	NM_001135998.3(NDUFB11):c.2T>A (p.Met1Lys)	NDUFB11	Uncertain significance	criteria provided, single submitter
1299427	NM_001135998.3(NDUFB11):c.83G>T (p.Arg28Leu)	NDUFB11	Uncertain significance	criteria provided, single submitter
3064543	NM_001135998.3(NDUFB11):c.261G>A (p.Met87Ile)	NDUFB11	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · 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
NDUFB11	Strong	X-linked	linear skin defects with multiple congenital anomalies 3	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NDUFB11	Orphanet:2556	Microphthalmia with linear skin defects syndrome
NDUFB11	Orphanet:2609	Isolated complex I deficiency

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
NDUFB11	HGNC:20372	ENSG00000147123	Q9NX14	NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDUFB11	NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial	Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis.

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)
NDUFB11	Other/Unknown	no		NADH_UbQ_OxRdtase_ESSS_su

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
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDUFB11	287	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDUFB11	1,844

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NDUFB11	Q9NX14	7

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 I biogenesis	1	165.5×	0.015	NDUFB11
Respiratory electron transport	1	95.2×	0.015	NDUFB11
Aerobic respiration and respiratory electron transport	1	88.5×	0.015	NDUFB11
Metabolism	1	11.6×	0.086	NDUFB11

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
proton motive force-driven mitochondrial ATP synthesis	1	263.3×	0.004	NDUFB11
aerobic respiration	1	247.8×	0.004	NDUFB11

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
NDUFB11	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
NDUFB11	4	Binding:4

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	NDUFB11

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)
NDUFB11	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.