NDUFA4

NDUFA4 mitochondrial complex associated

Basic information

Region (hg38): 7:10931943-10940153

Links

ENSG00000189043 ∙ NCBI:4697 ∙ OMIM:603833 ∙ HGNC:7687 ∙ Uniprot:O00483 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• Leigh syndrome (Limited), mode of inheritance: AR
• mitochondrial complex IV deficiency, nuclear type 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex IV deficiency, nuclear type 21	AR	Biochemical	In addition to other features, individuals have been described as presenting in infancy with lactic acidosis, necessitating treatment with sodium bicarbonate	Biochemical; Musculoskeletal; Neurologic	23746447

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDUFA4 gene.

• Mitochondrial complex 4 deficiency, nuclear type 21 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFA4 gene is commonly pathogenic or not. These statistics are base on transcript: . 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	3		4
missense			11	1		12
nonsense						0
start loss			1			1
frameshift		1				1
splice donor/acceptor (+/-2bp)	1	1				2
Total	1	2	13	4	0

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFA4	protein_coding	protein_coding	ENST00000339600	4	8306

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0239	0.788	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00789	43	43.1	0.997	0.00000219	525
Missense in Polyphen		5	6.9676	0.7176		126
Synonymous	-0.706	19	15.5	1.23	6.87e-7	148
Loss of Function	0.967	3	5.43	0.552	2.39e-7	61

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)	0.0000881	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytochrome c oxidase (COX, complex IV) is the terminal component of the mitochondrial respiratory chain that catalyzes the reduction of oxygen to water. Required for complex IV maintenance. {ECO:0000269|PubMed:22902835}.
• Disease: DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:23746447}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;TP53 Regulates Metabolic Genes;Transcriptional Regulation by TP53;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.230

Intolerance Scores

• loftool: 0.543
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.662
• hipred: N
• hipred_score: 0.267
• ghis: 0.634

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufa4

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;proton transmembrane transport
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex I;mitochondrial respiratory chain complex IV
• Molecular function: cytochrome-c oxidase activity;protein binding;NADH dehydrogenase (ubiquinone) activity;protein-containing complex binding