NDUFB11

Chr XX-linkedXLD

NADH:ubiquinone oxidoreductase subunit B11

Also known as: CI-ESSS, ESSS, MC1DN30, NP17.3, Np15, P17.3

NCBI Gene: 54539ENSG00000147123UniProt: Q9NX14

The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is located at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to ubiquinone. Mutations in the human gene are associated with linear skin defects with multiple congenital anomalies 3 and mitochondrial complex I deficiency. [provided by RefSeq, Dec 2016]

Primary Disease Associations & Inheritance

?Mitochondrial complex I deficiency, nuclear type 30MIM #301021
X-linked
Linear skin defects with multiple congenital anomalies 3MIM #300952
XLD
189
ClinVar variants
98
Pathogenic / LP
0.80
pLI score
1
Active trials
Clinical Summary— NDUFB11
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
98 Pathogenic / Likely Pathogenic· 51 VUS of 189 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.56LOEUF
pLI 0.804
Z-score 2.15
OE 0.00 (0.00–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.51Z-score
OE missense 0.82 (0.66–1.03)
54 obs / 65.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.66–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 0 / 5.4Missense obs/exp: 54 / 65.7Syn Z: -0.29

ClinVar Variant Classifications

189 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic86
Likely Pathogenic12
VUS51
Likely Benign30
Benign6
Conflicting4
86
Pathogenic
12
Likely Pathogenic
51
VUS
30
Likely Benign
6
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
85
0
86
Likely Pathogenic
5
2
5
0
12
VUS
1
36
13
1
51
Likely Benign
1
3
10
16
30
Benign
0
3
3
0
6
Conflicting
—4
Total84411617189

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NDUFB11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

NDUFB11-related mitochondrial complex I deficiency

strong
Monoallelic XLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersSkin
G2P ↗
splice region variantframeshift variantstop gainedmissense variantinframe deletion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Mitochondrial complex I deficiency, nuclear type 30

MIM #301021

Molecular basis of disorder known

X-linked

Linear skin defects with multiple congenital anomalies 3

MIM #300952

Molecular basis of disorder known

X-linked dominant
📖
GeneReview available — NDUFB11
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Penetrance, variable expressivity and monogenic neurodevelopmental disorders.
de Masfrand S et al.·Eur J Med Genet
2024
A novel mutation in NDUFB11 unveils a new clinical phenotype associated with lactic acidosis and sideroblastic anemia.
Torraco A et al.·Clin Genet
2017Case report
Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA): An Unconventional Mitochondrial Disorder.
Indrieri A et al.·Genes (Basel)
2021Review
Diverse phenotype in patients with complex I deficiency due to mutations in NDUFB11.
Reinson K et al.·Eur J Med Genet
2019Case report
Genetics of anophthalmia and microphthalmia. Part 2: Syndromes associated with anophthalmia-microphthalmia.
Slavotinek A·Hum Genet
2019Review
A Novel Mutation Associated with Neonatal Lethal Cardiomyopathy Leads to an Alternative Transcript Expression in the X-Linked Complex I NDUFB11 Gene.
Amate-García G et al.·Int J Mol Sci
2023
A novel gene signature to diagnose MASLD in metabolically unhealthy obese individuals.
Meroni M et al.·Biochem Pharmacol
2023
Mutations in NDUFB11, encoding a complex I component of the mitochondrial respiratory chain, cause microphthalmia with linear skin defects syndrome.
van Rahden VA et al.·Am J Hum Genet
2015
Effects of long-term low oxygen tension in human chondrosarcoma cells.
Piltti J et al.·J Cell Biochem
2018
X-linked NDUFA1 gene mutations associated with mitochondrial encephalomyopathy.
Fernandez-Moreira D et al.·Ann Neurol
2007
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SSR4 Promote Gastric Cancer Progression by Regulating Mitochondrial Oxidative Phosphorylation via NDUFB11 and ATP6AP1.
Li A et al.·Mol Carcinog
2025
Successful treatment of congenital sideroblastic anemia with low-dose decitabine in a patient with NDUFB11 gene mutation (c.276_278del): A case report.
Wang J et al.·Curr Res Transl Med
2025Case report
Case report: severe hypertrophic cardiomyopathy in a female neonate caused by de novo variant in NDUFB11.
Tariq J et al.·Eur Heart J Case Rep
2024🔓 Open AccessCase report
NDUFB11 and NDUFS3 regulate arterial atherosclerosis and venous thrombosis: Potential markers of atherosclerosis and venous thrombosis.
Ma YH et al.·Medicine (Baltimore)
2023
NDUFB11 and NDUFS3 play a role in atherosclerosis and chronic stress.
Yang Y et al.·Aging (Albany NY)
2023🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
AnemiaGeneticsErythropoiesis

Genomic of CONgenital Sideroblastic Anemias

RECRUITING
NCT07459816Phase NACentre Hospitalier Universitaire, AmiensStarted 2025-10-28
blood redrawal

External Resources

Links to major genomics databases and tools