NDUFAF3

NADH:ubiquinone oxidoreductase complex assembly factor 3, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 3:49020458-49023495

Previous symbols: [ "C3orf60" ]

Links

ENSG00000178057 ∙ NCBI:25915 ∙ OMIM:612911 ∙ HGNC:29918 ∙ Uniprot:Q9BU61 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex 1 deficiency, nuclear type 18 (Moderate), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 18 (Strong), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• Leigh syndrome with cardiomyopathy (Supportive), mode of inheritance: AR
• mitochondrial disease (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 18	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; 19463981
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 NDUFAF3 gene.

• not provided (59 variants)
• Mitochondrial complex I deficiency, nuclear type 1 (34 variants)
• Inborn genetic diseases (14 variants)
• not specified (9 variants)
• Mitochondrial complex 1 deficiency, nuclear type 18 (9 variants)
• Mitochondrial complex I deficiency (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFAF3 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	13	1	16
missense		1	36			37
nonsense		1	1			2
start loss	1					1
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	2		5
non coding			18	15		33
Total	1	3	57	28	1

Highest pathogenic variant AF is 0.0000131

Variants in NDUFAF3

This is a list of pathogenic ClinVar variants found in the NDUFAF3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-49021330-A-G			Likely benign (Aug 17, 2018)
3-49021360-G-T			Benign (Jun 28, 2018)
3-49021546-C-A			Likely benign (May 17, 2019)
3-49021642-G-A		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 17, 2018)
3-49021642-G-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
3-49021656-T-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
3-49021772-G-A		not specified	Likely benign (Mar 09, 2018)
3-49021775-A-G		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
3-49021776-C-T		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
3-49021782-C-G		Mitochondrial complex I deficiency, nuclear type 1	Conflicting classifications of pathogenicity (Jan 13, 2018)
3-49021896-C-T		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
3-49021904-C-T		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
3-49022002-A-T		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
3-49022018-G-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
3-49022019-G-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
3-49022027-G-A		Mitochondrial complex I deficiency	Uncertain significance (Jun 14, 2016)
3-49022146-T-C		Mitochondrial complex 1 deficiency, nuclear type 18	Pathogenic (Mar 01, 2020)
3-49022162-G-C			Likely benign (Nov 27, 2023)
3-49022170-G-T		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
3-49022173-T-C			Uncertain significance (Oct 01, 2020)
3-49022174-G-A			Likely benign (Dec 23, 2021)
3-49022176-A-G		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
3-49022178-C-G			Uncertain significance (Sep 07, 2022)
3-49022182-C-T		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
3-49022188-C-T		Inborn genetic diseases	Uncertain significance (Feb 06, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFAF3	protein_coding	protein_coding	ENST00000326925	5	3037

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00527	0.901	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.494	120	106	1.14	0.00000520	1150
Missense in Polyphen		47	39.436	1.1918		459
Synonymous	-0.472	49	45.0	1.09	0.00000216	407
Loss of Function	1.43	5	9.85	0.508	4.40e-7	91

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000380	0.000366
Ashkenazi Jewish	0.00241	0.00238
East Asian	0.00	0.00
Finnish	0.0000531	0.0000462
European (Non-Finnish)	0.0000893	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential factor for the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). {ECO:0000269|PubMed:19463981}.
• 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:19463981}. 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: 0.126

Intolerance Scores

• loftool: 0.404
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.42

Haploinsufficiency Scores

• pHI: 0.160
• hipred: N
• hipred_score: 0.239
• ghis: 0.575

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.860

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufaf3

Gene ontology

• Biological process: mitochondrial respiratory chain complex I assembly
• Cellular component: nucleus;mitochondrial inner membrane
• Molecular function: protein binding