NDUFB10

protein-coding

NADH:ubiquinone oxidoreductase subunit B10, the group of NADH:ubiquinone oxidoreductase supernumerary subunits

Gene summary

Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be involved in mitochondrial electron transport, NADH to ubiquinone and proton motive force-driven mitochondrial ATP synthesis. Located in mitochondrial inner membrane. Part of respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency 35. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_004548.3

Inheritance

ClinVar variants

P:1U:73B:30

Top phenotype

Mitochondrial complex I deficiency, nuclear type 35

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr16:1,959,538-1,961,975

External References & Databases

Ensembl (ENSG00000140990)

Transcript & Mutation Effects

hg38 • Region Span ~2.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mitochondrial complex 1 deficiency, nuclear type 35LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0033560

Submitter: Labcorp Genetics (formerly Invitae)

mitochondrial diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: PanelApp Australia

mitochondrial diseaseMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: ClinGen

The relationship between *NDUFB10* and primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of February 7, 2022. The *NDUFB10* gene encodes NADH:ubiquinone oxidoreductase (complex I) subunit B10, which is essential for complex I activity and assembly. Defects of this protein lead to complex I deficiency. The *NDUFB10* gene was first reported in relation to autosomal recessive mitochondrial disease in 2017 (PMID: 28040730). While various names have been given to the constellation of features seen in those with *NDUFB10*-related disease, pathogenic variants in this gene cause a primary mitochondrial disease. Therefore, the NDUFB10 phenotype has been lumped into one disease entity according to the ClinGen Lumping and Splitting Framework. Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included three variants identified in two cases in two publications (PMIDs: 28040730, 33169436). Features seen in these cases include severe infantile lactic acidosis, cardiomyopathy, intrauterine growth restriction, and poor growth after birth, liver involvement, and sensorineural hearing loss. Both affected infants died before 12 months of age. No segregation data were available. Loss of function is implicated as the mechanism of disease. This gene-disease association is also supported by known biochemical function, functional alteration in patient cells, functional alteration in non-patient cells, and animal models (PMIDs: 19672299, 27626371, 28040730, 32025618, 27509854). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on February 7, 2022 (SOP Version 8).

mitochondrial complex I deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0100133

Submitter: Orphanet

Clinical Genomic Database (CGD)

Mitochondrial complex I deficiency, nuclear type 35AR

Manifestation: Biochemical; Cardiovascular

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 28040730

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NDUFB10 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 84

not specifiedTotal: 53

NDUFB10-related disorderTotal: 2

Mitochondrial complex 1 deficiency, nuclear type 35Total: 1

Mitochondrial complex I deficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004548.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				20 clinvar	3 clinvar	23
missense	1 clinvar		68 clinvar	7 clinvar		76
nonsense						0
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	0	73	27	3	104

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004548.3	RefSeq	NP_004539.1	4	MANE Select
ENST00000268668.11	Ensembl	ENSP00000268668.6	4	MANE Select
ENST00000543683.6	Ensembl	ENSP00000445086.2	3	Standard
ENST00000543683.7	Ensembl	ENSP00000445086.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Retrograde endocannabinoid signaling - Homo sapiens (human)
Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
Alzheimer,s disease - Homo sapiens (human)
Huntington,s disease - Homo sapiens (human)
Thermogenesis - Homo sapiens (human)

Biological Process

mitochondrial electron transport, NADH to ubiquinone
mitochondrial respiratory chain complex I assembly

Molecular Function

protein binding
NADH dehydrogenase (ubiquinone) activity

Cellular Component

mitochondrial inner membrane
mitochondrial respiratory chain complex I

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000268668
Coding exons: 4
Length: 2468
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125745
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.15	139	106	1.31	0.00000581	1133
Missense (PolyPhen)		54	42.907	1.2585		450
Synonymous	-1.06	48	39.6	1.21	0.00000217	288
Loss of Function	1.38	5	9.61	0.520	4.12e-7	109

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000072	0.000070	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}.;

Recessive Scores

pRec: 0.0990

Intolerance Scores

LoFtool: 0.369
RVIS EVS: -0.47
RVIS percentile EVS: 23.04

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.204

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium