NDUFAF1

NADH:ubiquinone oxidoreductase complex assembly factor 1, the group of Mitochondrial complex I assembly complex|Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 15:41387218-41409403

Links

ENSG00000137806 ∙ NCBI:51103 ∙ OMIM:606934 ∙ HGNC:18828 ∙ Uniprot:Q9Y375 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 11 (Limited), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 11 (Limited), mode of inheritance: AR
• mitochondrial disease (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 11	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; 17557076; 21931170
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 NDUFAF1 gene.

• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFAF1 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			3	18	2	23
missense		1	72	6	4	83
nonsense			2			2
start loss	1					1
frameshift	1		2			3
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region				1		1
non coding			11	9	6	26
Total	2	1	93	33	12

Highest pathogenic variant AF is 0.0000263

Variants in NDUFAF1

This is a list of pathogenic ClinVar variants found in the NDUFAF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-41387294-G-A			Benign (Aug 10, 2019)
15-41387308-CA-C			Benign (Aug 10, 2019)
15-41387308-CAA-C			Benign (Aug 13, 2019)
15-41387308-C-CA			Benign (Aug 06, 2019)
15-41387456-C-T			Likely benign (Jul 14, 2022)
15-41387467-G-A		not specified	Uncertain significance (Jun 17, 2024)
15-41387470-C-T			Uncertain significance (Nov 29, 2023)
15-41387479-T-C		not specified	Uncertain significance (Jan 27, 2022)
15-41387487-G-C		not specified • Mitochondrial complex I deficiency, nuclear type 1	Benign (Jan 30, 2024)
15-41387502-T-G			Likely benign (Jan 11, 2024)
15-41387503-G-C			Benign (Oct 17, 2023)
15-41387509-G-T			Likely benign (Jan 24, 2024)
15-41387519-C-T		Mitochondrial complex I deficiency, nuclear type 1	Benign (Jan 30, 2024)
15-41387521-C-T			Uncertain significance (Jul 07, 2023)
15-41387522-G-A			Benign (Dec 13, 2023)
15-41387527-T-A		Mitochondrial complex I deficiency	Uncertain significance (Nov 02, 2022)
15-41387528-A-G			Likely benign (Nov 13, 2021)
15-41387534-T-C		not specified	Uncertain significance (Sep 11, 2023)
15-41387535-A-G		not specified	Uncertain significance (Jan 10, 2023)
15-41387553-C-A		not specified	Uncertain significance (Jun 18, 2021)
15-41387557-C-A		not specified	Uncertain significance (Apr 12, 2024)
15-41387558-C-T			Uncertain significance (Dec 27, 2023)
15-41387563-T-C		not specified	Uncertain significance (Dec 27, 2023)
15-41387573-G-A		not specified • Mitochondrial complex I deficiency, nuclear type 1 • NDUFAF1-related disorder	Conflicting classifications of pathogenicity (Apr 01, 2024)
15-41387592-A-G			Uncertain significance (Dec 03, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFAF1	protein_coding	protein_coding	ENST00000260361	4	15167

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00362	0.959	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.442	198	181	1.09	0.0000102	2170
Missense in Polyphen		65	62.583	1.0386		745
Synonymous	1.04	55	65.7	0.837	0.00000371	618
Loss of Function	1.82	6	13.1	0.458	7.11e-7	153

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000366	0.000365
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000879	0.0000879
Middle Eastern	0.000109	0.000109
South Asian	0.000425	0.000425
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Chaperone protein involved in the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). {ECO:0000250}.
• 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)

Intolerance Scores

• loftool: 0.699
• rvis_EVS: 0.58
• rvis_percentile_EVS: 82.17

Haploinsufficiency Scores

• pHI: 0.105
• hipred: N
• hipred_score: 0.241
• ghis: 0.468

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.626

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufaf1

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;mitochondrial respiratory chain complex I assembly;protein-containing complex assembly
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex I;cytosol
• Molecular function: protein binding;unfolded protein binding