NDUFAF2

NADH:ubiquinone oxidoreductase complex assembly factor 2, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 5:60945176-61154531

Previous symbols: [ "NDUFA12L" ]

Links

ENSG00000164182 ∙ NCBI:91942 ∙ OMIM:609653 ∙ HGNC:28086 ∙ Uniprot:Q8N183 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leigh syndrome (Strong), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 10 (Moderate), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 10 (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 10; Leigh syndrome	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; 16200211; 20571988; 20818383
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 NDUFAF2 gene.

• not provided (64 variants)
• Leigh syndrome (21 variants)
• Mitochondrial complex I deficiency, nuclear type 1 (15 variants)
• not specified (14 variants)
• Mitochondrial complex 1 deficiency, nuclear type 10 (11 variants)
• Inborn genetic diseases (8 variants)
• Mitochondrial complex I deficiency (4 variants)
• Cockayne syndrome type 1 (4 variants)
• Cockayne syndrome (1 variants)
• NDUFAF2-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFAF2 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				17	1	18
missense			19	2		21
nonsense	1	3	2	1		7
start loss		1				1
frameshift	5	1	1			7
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding			3	9	10	22
Total	6	6	26	29	11

Highest pathogenic variant AF is 0.0000460

Variants in NDUFAF2

This is a list of pathogenic ClinVar variants found in the NDUFAF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-60945190-G-C		Leigh syndrome • Mitochondrial complex I deficiency	Uncertain significance (Jun 14, 2016)
5-60945193-G-T		Mitochondrial complex I deficiency • Leigh syndrome	Uncertain significance (Jun 14, 2016)
5-60945223-G-A		not specified	Likely benign (Nov 01, 2017)
5-60945232-A-AGC		Mitochondrial complex I deficiency • Leigh syndrome	Uncertain significance (Jun 14, 2016)
5-60945256-A-T		Mitochondrial complex 1 deficiency, nuclear type 10	Likely pathogenic (Jun 29, 2023)
5-60945261-T-C			Likely benign (Jan 12, 2024)
5-60945263-GGT-G		Leigh syndrome	Likely pathogenic (Jan 06, 2023)
5-60945264-G-A		Mitochondrial complex 1 deficiency, nuclear type 10	Pathogenic (Jan 25, 2019)
5-60945268-C-T		Cockayne syndrome type 1	Uncertain significance (May 10, 2018)
5-60945273-T-G		Mitochondrial complex I deficiency • Leigh syndrome • Cockayne syndrome type 1	Uncertain significance (Aug 01, 2017)
5-60945279-C-T			Likely benign (Jan 13, 2023)
5-60945285-C-G			Likely benign (Oct 09, 2023)
5-60945286-T-C			Likely benign (Oct 10, 2023)
5-60945291-G-A		Mitochondrial complex 1 deficiency, nuclear type 10	Conflicting classifications of pathogenicity (Mar 25, 2024)
5-60945296-C-T			Uncertain significance (Sep 17, 2021)
5-60945297-G-A			Likely benign (Jul 08, 2022)
5-60945305-G-A		Mitochondrial complex 1 deficiency, nuclear type 10	Uncertain significance (Mar 05, 2023)
5-60945309-A-C			Uncertain significance (Jul 30, 2022)
5-60945315-G-A		not specified • Cockayne syndrome • Leigh syndrome • Mitochondrial complex I deficiency, nuclear type 1 • Mitochondrial complex 1 deficiency, nuclear type 10	Benign (Feb 01, 2024)
5-60945317-A-G		Inborn genetic diseases	Uncertain significance (Mar 20, 2022)
5-60945324-G-A			Likely benign (Dec 21, 2023)
5-60945330-G-A			Likely benign (Oct 06, 2023)
5-60945330-G-C			Likely benign (Dec 03, 2023)
5-60945334-C-T			Likely pathogenic (Nov 10, 2016)
5-60945335-A-T		not specified • Inborn genetic diseases	Conflicting classifications of pathogenicity (May 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFAF2	protein_coding	protein_coding	ENST00000296597	4	207898

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000208	0.282	125694	0	54	125748	0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0661	82	80.3	1.02	0.00000360	1103
Missense in Polyphen		24	22.649	1.0596		296
Synonymous	-0.645	32	27.7	1.16	0.00000130	291
Loss of Function	0.189	9	9.63	0.934	4.77e-7	119

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000536	0.000517
Ashkenazi Jewish	0.00	0.00
East Asian	0.000490	0.000489
Finnish	0.00	0.00
European (Non-Finnish)	0.000206	0.000202
Middle Eastern	0.000490	0.000489
South Asian	0.000312	0.000261
Other	0.000329	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a molecular chaperone for mitochondrial complex I assembly (PubMed:16200211). Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (PubMed:16200211, PubMed:27626371). {ECO:0000269|PubMed:16200211, ECO:0000269|PubMed:27626371}.
• 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:16200211}. 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:20571988}. 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.;Validated targets of C-MYC transcriptional activation (Consensus)

Recessive Scores

• pRec: 0.0524

Intolerance Scores

• loftool: 0.762
• rvis_EVS: 0.08
• rvis_percentile_EVS: 59.76

Haploinsufficiency Scores

• pHI: 0.0120
• hipred: N
• hipred_score: 0.150
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufaf2
• Phenotype: cellular phenotype; normal phenotype

Gene ontology

• Biological process: respiratory electron transport chain;mitochondrial respiratory chain complex I assembly;cellular respiration;negative regulation of insulin secretion involved in cellular response to glucose stimulus;reactive oxygen species metabolic process
• Cellular component: mitochondrion;mitochondrial inner membrane
• Molecular function: NADH dehydrogenase (ubiquinone) activity;electron transfer activity