NDUFA13

NADH:ubiquinone oxidoreductase subunit A13, the group of NADH:ubiquinone oxidoreductase supernumerary subunits

Basic information

Region (hg38): 19:19515736-19529054

Links

ENSG00000186010 ∙ NCBI:51079 ∙ OMIM:609435 ∙ HGNC:17194 ∙ Uniprot:Q9P0J0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thyroid Hurthle cell carcinoma (Limited), mode of inheritance: Unknown
• mitochondrial complex 1 deficiency, nuclear type 28 (Limited), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thyroid carcinoma, Hurthle cell	AD	Oncologic	Surveillance and/or awareness of thyroid cancer risk may allow early diagnosis and treatment of neoplasms, which may improve outcomes	Biochemical; Neurologic; Oncologic; Ophthalmologic	15841082; 25901006
In Mitochondrial complex I deficiency, 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 NDUFA13 gene.

• 6 conditions (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFA13 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				7	1	8
missense	1		27		1	29
nonsense						0
start loss			1			1
frameshift	1	1	1			3
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			3	1		4
non coding			1	6	2	9
Total	2	2	30	13	4

Highest pathogenic variant AF is 0.00000657

Variants in NDUFA13

This is a list of pathogenic ClinVar variants found in the NDUFA13 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-19516240-T-C		Mitochondrial complex 1 deficiency, nuclear type 28	Uncertain significance (Sep 02, 2021)
19-19516253-G-C		Hurthle cell carcinoma of thyroid	Pathogenic (May 23, 2005)
19-19516255-T-C		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
19-19516260-C-G			Uncertain significance (Aug 02, 2022)
19-19516266-A-G		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
19-19516267-T-C		Inborn genetic diseases	Uncertain significance (Jul 17, 2023)
19-19516268-G-A		Inborn genetic diseases	Uncertain significance (Aug 22, 2023)
19-19516268-G-T		Inborn genetic diseases	Uncertain significance (Jan 31, 2022)
19-19516269-C-A		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
19-19516270-C-T		Inborn genetic diseases	Uncertain significance (Nov 13, 2023)
19-19516276-C-CG		Hurthle cell carcinoma of thyroid • Mitochondrial complex 1 deficiency, nuclear type 28	Likely pathogenic (Oct 05, 2022)
19-19516279-G-C		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
19-19516282-G-A			Uncertain significance (Dec 11, 2023)
19-19516283-C-A			Conflicting classifications of pathogenicity (Jan 22, 2024)
19-19516289-G-T			Likely benign (Apr 01, 2022)
19-19516304-AC-A			Uncertain significance (May 05, 2022)
19-19516312-T-G		NDUFA13-related disorder	Benign (Aug 10, 2023)
19-19516329-T-G			Uncertain significance (Jul 05, 2022)
19-19516333-G-A		Hurthle cell carcinoma of thyroid • Mitochondrial complex 1 deficiency, nuclear type 28	Likely pathogenic (Oct 16, 2023)
19-19516335-C-G			Uncertain significance (Aug 04, 2023)
19-19526169-C-T			Benign (Jan 22, 2024)
19-19526177-C-T			Likely benign (Jan 29, 2024)
19-19526185-A-G			Uncertain significance (Nov 27, 2023)
19-19526194-T-C		6 conditions • Mitochondrial complex 1 deficiency, nuclear type 28	Pathogenic (Jun 09, 2020)
19-19526212-C-A			Uncertain significance (Sep 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFA13	protein_coding	protein_coding	ENST00000507754	5	17741

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000380	0.217	125667	0	38	125705	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.904	121	96.1	1.26	0.00000664	923
Missense in Polyphen		54	38.568	1.4001		353
Synonymous	-1.19	48	38.6	1.24	0.00000280	273
Loss of Function	-0.153	8	7.55	1.06	3.31e-7	84

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000310	0.000304
Ashkenazi Jewish	0.000497	0.000496
East Asian	0.000109	0.000109
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000232	0.000211
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis (PubMed:27626371). 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:27626371). Involved in the interferon/all-trans-retinoic acid (IFN/RA) induced cell death. This apoptotic activity is inhibited by interaction with viral IRF1. Prevents the transactivation of STAT3 target genes. May play a role in CARD15-mediated innate mucosal responses and serve to regulate intestinal epithelial cell responses to microbes (PubMed:15753091). {ECO:0000269|PubMed:12628925, ECO:0000269|PubMed:12867595, ECO:0000269|PubMed:15753091, ECO:0000269|PubMed:27626371}.
• Disease: DISEASE: Hurthle cell thyroid carcinoma (HCTC) [MIM:607464]: A rare type of thyroid cancer accounting for only about 3-10% of all differentiated thyroid cancers. These neoplasms are considered a variant of follicular carcinoma of the thyroid and are referred to as follicular carcinoma, oxyphilic type. {ECO:0000269|PubMed:15841082}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Note=Defects in NDUFA13 are a cause of a mitochondrial complex I deficiency characterized by early onset hypotonia, dyskinesia and sensorial deficiencies, as well as a severe optic neuropathy. {ECO:0000269|PubMed:25901006}.
• Pathway: Retrograde endocannabinoid signaling - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Nucleotide-binding Oligomerization Domain (NOD) pathway;EGF-EGFR Signaling Pathway;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: 0.146

Intolerance Scores

• loftool: 0.678
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.19

Haploinsufficiency Scores

• pHI: 0.0643
• hipred: N
• hipred_score: 0.131
• ghis: 0.553

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufa13
• Phenotype: cellular phenotype; growth/size/body region phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: positive regulation of peptidase activity;negative regulation of cell growth;mitochondrial respiratory chain complex I assembly;cellular response to interferon-beta;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;protein insertion into mitochondrial inner membrane;positive regulation of protein catabolic process;negative regulation of transcription, DNA-templated;oxidation-reduction process;cellular response to retinoic acid;reactive oxygen species metabolic process;apoptotic signaling pathway;extrinsic apoptotic signaling pathway;negative regulation of intrinsic apoptotic signaling pathway
• Cellular component: nucleoplasm;cytoplasm;mitochondrion;mitochondrial inner membrane;mitochondrial respirasome;mitochondrial respiratory chain complex I;integral component of membrane;mitochondrial membrane
• Molecular function: NADH dehydrogenase activity;protein binding;ATP binding;NADH dehydrogenase (ubiquinone) activity