NDUFAF4

NADH:ubiquinone oxidoreductase complex assembly factor 4, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 6:96889315-96897891

Previous symbols: [ "C6orf66" ]

Links

ENSG00000123545 ∙ NCBI:29078 ∙ OMIM:611776 ∙ HGNC:21034 ∙ Uniprot:Q9P032 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex 1 deficiency, nuclear type 15 (Strong), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 15	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; 18179882
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 NDUFAF4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFAF4 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	5	3	10
missense			19	2	1	22
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			40	16	11	67
Total	0	0	62	23	15

Variants in NDUFAF4

This is a list of pathogenic ClinVar variants found in the NDUFAF4 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-96889356-A-G		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
6-96889376-C-T		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
6-96889377-A-G		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
6-96889433-A-G		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
6-96889462-A-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
6-96889617-T-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
6-96889623-A-G		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
6-96889657-A-G		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
6-96889661-C-T		Mitochondrial complex I deficiency, nuclear type 1	Benign (Jan 12, 2018)
6-96889729-C-A		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
6-96889736-T-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
6-96889741-C-T		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
6-96889742-G-A		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
6-96889770-C-T		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
6-96889805-C-T		Mitochondrial complex I deficiency, nuclear type 1	Likely benign (Jan 13, 2018)
6-96889857-T-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
6-96889890-C-T		Mitochondrial complex I deficiency, nuclear type 1	Likely benign (Apr 27, 2017)
6-96889891-G-A		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
6-96889901-T-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
6-96889950-T-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
6-96889983-T-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
6-96890042-A-C		Mitochondrial complex I deficiency, nuclear type 1	Likely benign (Jan 13, 2018)
6-96890051-T-C		Mitochondrial complex I deficiency	Uncertain significance (Jun 14, 2016)
6-96890096-A-G		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
6-96890118-T-G		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFAF4	protein_coding	protein_coding	ENST00000316149	3	8569

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.553	0.435	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0626	90	91.7	0.982	0.00000451	1154
Missense in Polyphen		24	26.49	0.90602		337
Synonymous	-0.383	37	34.2	1.08	0.00000176	324
Loss of Function	2.02	1	6.61	0.151	2.91e-7	80

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). May be involved in cell proliferation and survival of hormone-dependent tumor cells. May be a regulator of breast tumor cell invasion. {ECO:0000269|PubMed:14871833, ECO:0000269|PubMed:17001319, ECO:0000269|PubMed:18179882}.
• 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:18179882}. 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: 0.0942

Intolerance Scores

• loftool: 0.198
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.95

Haploinsufficiency Scores

• pHI: 0.224
• hipred: N
• hipred_score: 0.217
• ghis: 0.544

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.382

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufaf4

Gene ontology

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