NDUFB3

NADH:ubiquinone oxidoreductase subunit B3, the group of NADH:ubiquinone oxidoreductase supernumerary subunits

Basic information

Region (hg38): 2:201071433-201085750

Links

ENSG00000119013 ∙ NCBI:4709 ∙ OMIM:603839 ∙ HGNC:7698 ∙ Uniprot:O43676 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex 1 deficiency, nuclear type 25 (Moderate), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 25 (Strong), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 25 (Definitive), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 25	AR	General	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	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	11743516; 15534765; 22277967
Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDUFB3 gene.

• Mitochondrial complex 1 deficiency, nuclear type 25 (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFB3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense		1	18			19
nonsense		1				1
start loss						0
frameshift	2	1				3
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region					3	3
non coding				2	5	7
Total	2	3	19	4	5

Variants in NDUFB3

This is a list of pathogenic ClinVar variants found in the NDUFB3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-201072325-T-C		not specified	Benign (Sep 17, 2015)
2-201072375-A-G		not specified	Benign (Sep 17, 2015)
2-201078574-A-G			Benign (Jul 09, 2018)
2-201078708-A-G			Benign (Jun 14, 2018)
2-201078886-G-A		Inborn genetic diseases	Uncertain significance (Aug 09, 2021)
2-201078891-T-A			Uncertain significance (Sep 16, 2022)
2-201078894-A-G		not specified	Likely benign (Dec 19, 2021)
2-201078894-ACATGGACATGAG-A			Uncertain significance (Jul 19, 2022)
2-201078895-C-T			Uncertain significance (Aug 09, 2022)
2-201078897-T-G		Inborn genetic diseases	Uncertain significance (Nov 01, 2022)
2-201078901-C-T			Conflicting classifications of pathogenicity (Dec 27, 2023)
2-201078902-A-C			Uncertain significance (Mar 20, 2022)
2-201078937-T-G			Uncertain significance (Dec 03, 2021)
2-201078943-C-T		Mitochondrial complex 1 deficiency, nuclear type 25	Likely pathogenic (Apr 22, 2022)
2-201078946-T-C		Mitochondrial complex I deficiency • Inborn genetic diseases • Mitochondrial complex 1 deficiency, nuclear type 25	Pathogenic/Likely pathogenic (Apr 11, 2023)
2-201078957-A-C			Uncertain significance (May 05, 2022)
2-201078970-G-A			Uncertain significance (Nov 01, 2022)
2-201078978-C-G		Inborn genetic diseases	Uncertain significance (May 09, 2022)
2-201078985-A-C			Uncertain significance (Dec 23, 2021)
2-201078995-CA-C		Mitochondrial complex 1 deficiency, nuclear type 25	Pathogenic (Feb 02, 2022)
2-201079018-G-A		Developmental cataract;Developmental regression;Death in childhood;Seizure	Uncertain significance (Dec 20, 2019)
2-201079021-C-A		Inborn genetic diseases	Uncertain significance (Jun 29, 2021)
2-201079035-A-C			Likely benign (Aug 16, 2022)
2-201079273-C-T			Likely benign (Jun 14, 2018)
2-201085443-CT-C			Benign (Nov 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFB3	protein_coding	protein_coding	ENST00000237889	2	14318

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000161	0.142	125540	0	41	125581	0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.316	45	51.4	0.876	0.00000234	650
Missense in Polyphen		12	14.551	0.82471		176
Synonymous	0.982	12	17.2	0.699	7.42e-7	170
Loss of Function	-1.10	6	3.72	1.61	1.57e-7	47

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000390	0.000389
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000221	0.000220
Middle Eastern	0.0000544	0.0000544
South Asian	0.000140	0.000131
Other	0.000163	0.000163

dbNSFP

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}.
• Disease: DISEASE: Mitochondrial complex I deficiency (MT-C1D) [MIM:252010]: A disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. {ECO:0000269|PubMed:22499348, ECO:0000269|PubMed:27091925}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: 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);Oxidative phosphorylation - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Electron Transport Chain;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Complex I biogenesis;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Intolerance Scores

• loftool: 0.688
• rvis_EVS: 0.21
• rvis_percentile_EVS: 67.72

Haploinsufficiency Scores

• pHI: 0.0717
• hipred: N
• hipred_score: 0.198
• ghis: 0.509

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufb3

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;mitochondrial respiratory chain complex I assembly
• Cellular component: mitochondrial inner membrane;mitochondrial respiratory chain complex I;integral component of membrane
• Molecular function: NADH dehydrogenase (ubiquinone) activity