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

not_provided (69 variants)
Inborn_genetic_diseases (27 variants)
NDUFB8-related_disorder (11 variants)
Mitochondrial_complex_I_deficiency,_nuclear_type_32 (9 variants)

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. These statistics are base on transcript: NM_000005004.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	18 clinvar	2 clinvar	21
missense	3 clinvar		43 clinvar	3 clinvar	3 clinvar	52
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar	2 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	3	1	47	21	5

Highest pathogenic variant AF is 0.00000137108

Loading clinvar variants...

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