NDUFA4

Rationale: In addition to other features, individuals have been described as presenting in infancy with lactic acidosis, necessitating treatment with sodium bicarbonate

Refs: 23746447

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NDUFA4 variants in ClinVar

1 Conditions Cataloged

Mitochondrial complex 4 deficiency, nuclear type 21Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript . 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			1 clinvar	3 clinvar		4
missense			11 clinvar	1 clinvar		12
nonsense						0
start loss			1 clinvar			1
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar				2
Total	1	2	13	4	0	20

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 0 of 0 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
No transcripts match your selected source or search query.

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
proton transmembrane transport

Molecular Function

cytochrome-c oxidase activity
protein binding
NADH dehydrogenase (ubiquinone) activity
protein-containing complex binding

Cellular Component

mitochondrion
mitochondrial inner membrane
mitochondrial respiratory chain complex I
mitochondrial respiratory chain complex IV

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000339600
Coding exons: 4
Length: 8306
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.00789	43	43.1	0.997	0.00000219	525
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.230

Intolerance Scores

LoFtool: 0.543
RVIS EVS: -0.1
RVIS percentile EVS: 46.2

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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