NDUFB8

NADH:ubiquinone oxidoreductase subunit B8, the group of NADH:ubiquinone oxidoreductase supernumerary subunits

Basic information

Region (hg38): 10:100523668-100530000

Links

ENSG00000166136 ∙ NCBI:4714 ∙ OMIM:602140 ∙ HGNC:7703 ∙ Uniprot:O95169 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex I deficiency, nuclear type 1 (Strong), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 32 (Moderate), mode of inheritance: AR
• Leigh syndrome with cardiomyopathy (Supportive), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 32 (Limited), mode of inheritance: Unknown
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 32	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; Neurologic	29429571

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDUFB8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFB8 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			1	15	2	18
missense			28	3	3	34
nonsense			1			1
start loss						0
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	4		6
non coding				8	3	11
Total	0	1	31	26	8

Variants in NDUFB8

This is a list of pathogenic ClinVar variants found in the NDUFB8 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-100523841-A-T			Uncertain significance (May 16, 2023)
10-100523847-T-C		Inborn genetic diseases	Uncertain significance (Sep 02, 2024)
10-100523859-C-T		Inborn genetic diseases	Uncertain significance (Sep 07, 2022)
10-100523882-A-G			Likely benign (Jul 24, 2022)
10-100523884-C-T			Uncertain significance (Feb 08, 2023)
10-100523885-G-A		NDUFB8-related disorder	Benign (Jan 18, 2024)
10-100523890-G-A			Uncertain significance (Aug 04, 2023)
10-100523925-G-A		Inborn genetic diseases	Uncertain significance (Feb 27, 2024)
10-100523926-G-A		Inborn genetic diseases	Uncertain significance (Feb 27, 2024)
10-100523933-C-G			Likely benign (Oct 03, 2023)
10-100524148-GAGA-G		NDUFB8-related disorder	Likely benign (Nov 21, 2019)
10-100526388-C-T			Benign (Jan 11, 2024)
10-100526413-C-G			Uncertain significance (Sep 01, 2021)
10-100526422-C-T		NDUFB8-related disorder	Benign (Nov 15, 2023)
10-100526423-G-A			Likely benign (Aug 14, 2023)
10-100526424-T-C			Uncertain significance (Jun 05, 2022)
10-100526425-C-G		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
10-100526435-G-C		Mitochondrial complex 1 deficiency, nuclear type 32	Pathogenic (Dec 13, 2018)
10-100526438-C-G		Inborn genetic diseases	Uncertain significance (Mar 19, 2024)
10-100526440-T-C			Uncertain significance (Sep 07, 2022)
10-100526447-C-A			Uncertain significance (Oct 13, 2023)
10-100526464-C-T			Uncertain significance (Dec 28, 2023)
10-100526465-G-T			Uncertain significance (Dec 26, 2020)
10-100526468-G-A			Likely benign (Jul 05, 2022)
10-100526468-G-C			Likely benign (Oct 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFB8	protein_coding	protein_coding	ENST00000299166	5	22555

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00747	0.931	125737	0	9	125746	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.113	121	118	1.03	0.00000611	1222
Missense in Polyphen		37	35.475	1.043		446
Synonymous	0.391	41	44.3	0.925	0.00000238	344
Loss of Function	1.61	5	10.7	0.467	4.57e-7	115

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000713	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.00	0.00

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}.
• 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;Oxidative phosphorylation;Metabolism of proteins;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Mitochondrial protein import;Complex I biogenesis;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.127

Intolerance Scores

• loftool: 0.334
• rvis_EVS: -0.18
• rvis_percentile_EVS: 39.95

Haploinsufficiency Scores

• pHI: 0.121
• hipred: N
• hipred_score: 0.163
• ghis: 0.545

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.642

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufb8
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype; hematopoietic system phenotype

Gene ontology

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