NDUFA5

protein-coding

NADH:ubiquinone oxidoreductase subunit A5, the group of NADH:ubiquinone oxidoreductase supernumerary subunits

Gene summary

This nuclear gene encodes a conserved protein that comprises the B13 subunit of complex I of the mitochondrial respiratory chain. The encoded protein localizes to the inner mitochondrial membrane, where it is thought to aid in the transfer of electrons from NADH to ubiquinone. Alternative splicing results in multiple transcript variants. There are numerous pseudogenes of this gene on chromosomes 1, 3, 6, 8, 9, 11, 12, and 16. [provided by RefSeq, Apr 2014]

MANE transcript

NM_005000.5

Inheritance

—

ClinVar variants

U:13B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr7:123,536,997-123,557,904

External References & Databases

Ensembl (ENSG00000128609)

Transcript & Mutation Effects

hg38 • Region Span ~20.9 kb

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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 NDUFA5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 10

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005000.5. 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			11 clinvar		1 clinvar	12
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	13	0	1	14

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005000.5	RefSeq	NP_004991.1	5	MANE Select
ENST00000355749.7	Ensembl	ENSP00000347988.2	5	MANE Select
NM_001282419.3	RefSeq	NP_001269348.1	4	Standard
NM_001282420.3	RefSeq	NP_001269349.1	5	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

protein binding
NADH dehydrogenase (ubiquinone) activity

Cellular Component

mitochondrial inner membrane
mitochondrial respiratory chain complex I

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355749
Coding exons: 5
Length: 21259
Individuals with no LoFs: 125713
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125741
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.200	55	59.3	0.927	0.00000275	745
Missense (PolyPhen)		10	9.9194	1.0081		142
Synonymous	-0.167	23	22.0	1.05	0.00000113	206
Loss of Function	0.876	5	7.61	0.657	3.20e-7	97

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0.0014	0.0014	notable
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	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}.;

Intolerance Scores

LoFtool: 0.499
RVIS EVS: -0.19
RVIS percentile EVS: 39.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.473

Gene Damage Prediction

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