NDUFB4

protein-coding

NADH:ubiquinone oxidoreductase subunit B4, the group of NADH:ubiquinone oxidoreductase supernumerary subunits

Gene summary

This gene encodes a non-catalytic subunit of the multisubunit NADH:ubiquinone oxidoreductase, the first enzyme complex in the mitochondrial electron transport chain (complex I). Mammalian complex I is composed of 45 different subunits and transfers electrons from NADH to ubiquinone. [provided by RefSeq, Dec 2009]

MANE transcript

NM_004547.6

Inheritance

—

ClinVar variants

U:10B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr3:120,596,328-120,602,507

External References & Databases

Ensembl (ENSG00000065518)

Transcript & Mutation Effects

hg38 • Region Span ~6.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NDUFB4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 11

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004547.6. 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						0
missense			9 clinvar	3 clinvar		12
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	10	3	0	13

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004547.6	RefSeq	NP_004538.2	3	MANE Select
ENST00000184266.3	Ensembl	ENSP00000184266.2	3	MANE Select
NM_001168331.2	RefSeq	NP_001161803.1	2	Standard
ENST00000461682.1	Ensembl	ENSP00000417714.1	1	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
response to oxidative stress
mitochondrial respiratory chain complex I assembly

Molecular Function

NADH dehydrogenase (ubiquinone) activity

Cellular Component

mitochondrion
mitochondrial inner membrane
mitochondrial respiratory chain complex I
integral component of membrane
nuclear membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000184266
Coding exons: 3
Length: 6192
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125747
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.386	82	72.7	1.13	0.00000341	816
Missense (PolyPhen)		20	22.111	0.90453		287
Synonymous	0.323	27	29.2	0.924	0.00000130	267
Loss of Function	0.852	4	6.31	0.634	2.87e-7	71

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00020	0.00020	rare
South Asian	0.00033	0.00033	rare
Other	0.00033	0.00033	rare

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: 0.129

Intolerance Scores

LoFtool: 0.477
RVIS EVS: -0.12
RVIS percentile EVS: 44.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.914

Gene Damage Prediction

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