NDUFB11

Chr XX-linkedXLD

NADH:ubiquinone oxidoreductase subunit B11

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

NCBI Gene: 54539 ENSG00000147123 UniProt: Q9NX14 OMIM: 300403

The NDUFB11 protein is an accessory subunit of mitochondrial complex I (NADH dehydrogenase), which transfers electrons from NADH to ubiquinone in the respiratory chain. Mutations cause X-linked mitochondrial complex I deficiency and linear skin defects with multiple congenital anomalies 3, affecting both metabolic and developmental processes. This gene shows high constraint against loss-of-function variants (LOEUF 0.556), indicating that such mutations are likely to have significant clinical consequences.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Mitochondrial complex I deficiency, nuclear type 30MIM #301021

X-linked

Linear skin defects with multiple congenital anomalies 3MIM #300952

XLD

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mitochondrial disease · XL · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.56

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — NDUFB11

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.51Z-score

OE missense 0.82 (0.66–1.03)

54 obs / 65.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.56)

0≤0.351.4

Missense OE?0.82 (0.66–1.03)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 0 / 5.4Missense obs/exp: 54 / 65.7Syn Z: -0.29

Background carrier burden — how many people carry a rare variant somewhere in NDUFB11?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 350

141 rare PASS variants

Rare truncating (LoF)

1 in 73,000

4 rare PASS variants

Rare synonymous (reference)

1 in 1,100

40 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NDUFB11. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 360	1 in 75,000
South Asian	~36k	1 in 370	≈ 1 in 18,000
Remaining (unassigned)	~31k	1 in 440	none seen
European (Finnish)	~27k	1 in 1,900	none seen
Admixed American	~23k	1 in 410	none seen
African / African American	~21k	1 in 210	none seen
East Asian	~20k	1 in 260	none seen
Ashkenazi Jewish	~13k	≈ 1 in 3,100	none seen
Middle Eastern	~2,758	1 in 370	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 3 coding exons well covered in gnomAD exomes. Genomes: 2 of 3 (exon 1 below).? see exons ↓