NDUFAF8

NADH:ubiquinone oxidoreductase complex assembly factor 8, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 17:81239305-81241310

Previous symbols: [ "C17orf89" ]

Links

ENSG00000224877 ∙ NCBI:284184 ∙ OMIM:618461 ∙ HGNC:33551 ∙ Uniprot:A1L188 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex 1 deficiency, nuclear type 34 (Moderate), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR
• Leigh syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 34	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; Neurologic; Ophthalmologic	31866046
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 NDUFAF8 gene.

• Mitochondrial complex 1 deficiency, nuclear type 34 (3 variants)
• Mitochondrial disease (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFAF8 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						0
missense		1	5	1		7
nonsense						0
start loss	2					2
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding		1			6	7
Total	3	2	5	1	6

Highest pathogenic variant AF is 0.00000657

Variants in NDUFAF8

This is a list of pathogenic ClinVar variants found in the NDUFAF8 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-81239341-C-T			Benign (May 11, 2021)
17-81239364-A-C		Mitochondrial complex 1 deficiency, nuclear type 34	Pathogenic (Mar 30, 2022)
17-81239364-A-G		Mitochondrial disease • Mitochondrial complex 1 deficiency, nuclear type 34	Pathogenic (Oct 09, 2019)
17-81239380-C-A		NDUFAF8-related disorder	Uncertain significance (Mar 13, 2023)
17-81239382-G-T		Inborn genetic diseases	Uncertain significance (Sep 27, 2021)
17-81239391-C-T		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
17-81239402-C-CCGCCTCCG		Mitochondrial complex 1 deficiency, nuclear type 34 • Mitochondrial disease	Pathogenic (Oct 09, 2019)
17-81239442-G-A		Inborn genetic diseases	Likely benign (Jun 05, 2024)
17-81239505-G-A			Benign (May 10, 2021)
17-81239603-G-T		NDUFAF8-related disorder	Likely benign (Jul 14, 2020)
17-81239604-GC-G			Uncertain significance (Jun 24, 2024)
17-81239620-T-C			Uncertain significance (Feb 01, 2025)
17-81239648-C-G		Mitochondrial disease • Mitochondrial complex 1 deficiency, nuclear type 34	Likely pathogenic (Oct 09, 2019)
17-81239653-C-A			Uncertain significance (Jan 01, 2023)
17-81239704-C-G			Benign (May 10, 2021)
17-81239762-T-C			Benign (May 10, 2021)
17-81239949-C-T		Mitochondrial disease • Mitochondrial complex 1 deficiency, nuclear type 34 • NDUFAF8-related disorder	Pathogenic/Likely pathogenic (Aug 01, 2024)
17-81240922-A-G			Benign (May 10, 2021)
17-81240994-A-C		Inborn genetic diseases	Uncertain significance (Aug 16, 2021)
17-81241127-C-T		NDUFAF8-related disorder	Benign (Jun 12, 2020)
17-81241219-C-T			Benign (May 22, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFAF8	protein_coding	protein_coding	ENST00000431388	3	2043

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.143	0.642	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.395	21	26.7	0.785	0.00000134	451
Missense in Polyphen		6	6.8578	0.87492		116
Synonymous	0.241	11	12.1	0.912	6.43e-7	150
Loss of Function	0.626	1	1.94	0.515	8.30e-8	36

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)	0.00	0.00
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, MT-ND1) (PubMed:27499296). Required to stabilize NDUFAF5 (PubMed:27499296). {ECO:0000269|PubMed:27499296}.

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.144
• ghis: 0.653

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Ndufaf8

Gene ontology

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