NDUFA3

protein-coding

NADH:ubiquinone oxidoreductase subunit A3, 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. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_004542.4

Inheritance

ClinVar variants

U:13B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr19:54,102,728-54,109,257

External References & Databases

Ensembl (ENSG00000170906)

Transcript & Mutation Effects

hg38 • Region Span ~6.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Leigh syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0009723

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NDUFA3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 14

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004542.4. 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			13 clinvar	1 clinvar		14
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	13	1	0	14

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004542.4	RefSeq	NP_004533.1	4	MANE Select
ENST00000485876.6	Ensembl	ENSP00000418438.1	4	MANE Select
ENST00000303553.5	Ensembl	ENSP00000474408.1	2	Standard
ENST00000391762.5	Ensembl	ENSP00000375642.1	4	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

NADH dehydrogenase (ubiquinone) activity

Cellular Component

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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000485876
Coding exons: 4
Length: 6529
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125740
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.394	57	49.2	1.16	0.00000275	539
Missense (PolyPhen)		12	9.9424	1.207		129
Synonymous	0.387	19	21.3	0.893	0.00000127	155
Loss of Function	0.954	2	4.08	0.490	1.72e-7	53

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000064	0.000062	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
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}.;

Intolerance Scores

LoFtool: 0.394
RVIS EVS: 0.19
RVIS percentile EVS: 66.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.482

Gene Damage Prediction

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