NDUFAF5

NADH:ubiquinone oxidoreductase complex assembly factor 5, the group of Seven-beta-strand methyltransferase motif containing|Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 20:13785007-13821580

Previous symbols: [ "C20orf7" ]

Links

ENSG00000101247

∙ NCBI:79133 ∙ OMIM:612360 ∙ HGNC:15899 ∙ Uniprot:Q5TEU4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

mitochondrial complex I deficiency, nuclear type 16 (Strong), mode of inheritance: AR
mitochondrial complex I deficiency, nuclear type 16 (Strong), mode of inheritance: AR
mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
Leigh syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 16	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	11743516; 18940309; 19542079; 21607760; 29581464; 30473481
Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDUFAF5 gene.

not_provided (421 variants)
Mitochondrial_complex_I_deficiency,_nuclear_type_16 (88 variants)
Mitochondrial_complex_I_deficiency (55 variants)
Inborn_genetic_diseases (46 variants)
Leigh_syndrome (35 variants)
not_specified (29 variants)
NDUFAF5-related_disorder (9 variants)
Mitochondrial_complex_I_deficiency,_nuclear_type_1 (5 variants)
Leber_plus_disease (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFAF5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024120.5. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	2 clinvar	149 clinvar	3 clinvar	155
missense	2 clinvar	17 clinvar	103 clinvar	8 clinvar		130
nonsense	8 clinvar	12 clinvar				20
start loss	3	1				4
frameshift	19 clinvar	28 clinvar	1 clinvar			48
splice donor/acceptor (+/-2bp)	1 clinvar	24 clinvar	1 clinvar	1 clinvar		27
Total	33	83	107	158	3

Highest pathogenic variant AF is 0.00047199594

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFAF5	protein_coding	protein_coding	ENST00000378106	11	33472

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.11e-10	0.296	125668	0	80	125748	0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.150	187	193	0.970	0.00000968	2234
Missense in Polyphen		48	66.581	0.72093		754
Synonymous	-0.408	74	69.7	1.06	0.00000359	659
Loss of Function	0.851	17	21.2	0.801	9.69e-7	258

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000651	0.000651
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000940	0.0000924
European (Non-Finnish)	0.000399	0.000396
Middle Eastern	0.000218	0.000217
South Asian	0.000262	0.000261
Other	0.000492	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Arginine hydroxylase involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) at early stages (PubMed:18940309, PubMed:27226634). Acts by mediating hydroxylation of 'Arg-111' of NDUFS7 (PubMed:27226634). May also have methyltransferase activity (Probable). {ECO:0000269|PubMed:18940309, ECO:0000269|PubMed:27226634, ECO:0000305}.;
Disease: DISEASE: Mitochondrial complex I deficiency (MT-C1D) [MIM:252010]: A disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. {ECO:0000269|PubMed:18940309}. Note=The disease is caused by mutations affecting the gene represented in this entry.; 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:19542079, ECO:0000269|PubMed:21607760}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Thermogenesis - Homo sapiens (human);Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Complex I biogenesis;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

pRec: 0.105

Intolerance Scores

loftool
rvis_EVS: -0.8
rvis_percentile_EVS: 12.33

Haploinsufficiency Scores

pHI: 0.0855
hipred: N
hipred_score: 0.197
ghis: 0.607

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred
gene_indispensability_score

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Ndufaf5
Phenotype

Gene ontology

Biological process: peptidyl-arginine hydroxylation;methylation;mitochondrial respiratory chain complex I assembly;oxidation-reduction process
Cellular component: mitochondrion;mitochondrial inner membrane;extrinsic component of mitochondrial inner membrane
Molecular function: molecular_function;protein binding;methyltransferase activity;oxidoreductase activity