NUBPL

NUBP iron-sulfur cluster assembly factor, mitochondrial, the group of Mitochondrial respiratory chain complex assembly factors|Mitochondrial iron-sulfur assembly components

Basic information

Region (hg38): 14:31489955-31861224

Previous symbols: [ "C14orf127" ]

Links

ENSG00000151413 ∙ NCBI:80224 ∙ OMIM:613621 ∙ HGNC:20278 ∙ Uniprot:Q8TB37 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex I deficiency, nuclear type 1 (Definitive), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 21 (Strong), 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
Mitochondrial complex I deficiency, nuclear type 21	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; Musculoskeletal; Neurologic	11743516; 20818383; 23553477; 31917109
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 NUBPL gene.

• not provided (143 variants)
• Mitochondrial complex I deficiency, nuclear type 1 (83 variants)
• Mitochondrial complex I deficiency (19 variants)
• Mitochondrial complex 1 deficiency, nuclear type 21 (18 variants)
• Inborn genetic diseases (15 variants)
• not specified (13 variants)
• Mitochondrial oxidative phosphorylation disorder (1 variants)
• NUBPL-related condition (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NUBPL 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			4	15		19
missense	1	1	49	2		53
nonsense		1	2			3
start loss		1				1
frameshift	2		1			3
inframe indel						0
splice donor/acceptor (+/-2bp)		2	1			3
splice region			6	3	3	12
non coding			53	26	47	126
Total	3	5	110	43	47

Highest pathogenic variant AF is 0.0000197

Variants in NUBPL

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

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

Position	Type	Phenotype	Significance	ClinVar
14-31561083-GT-G			Benign (Jun 29, 2018)
14-31561189-T-G			Benign (Aug 03, 2018)
14-31561401-G-A		Mitochondrial complex I deficiency	Uncertain significance (Jun 14, 2016)
14-31561415-A-G		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
14-31561427-A-G		Mitochondrial complex I deficiency, nuclear type 1	Conflicting classifications of pathogenicity (Apr 13, 2020)
14-31561433-C-T		Mitochondrial complex I deficiency, nuclear type 1 • not specified • NUBPL-related disorder	Conflicting classifications of pathogenicity (Apr 01, 2022)
14-31561439-C-T		not specified • Mitochondrial complex I deficiency, nuclear type 1	Conflicting classifications of pathogenicity (Jan 01, 2024)
14-31561441-T-C		Mitochondrial oxidative phosphorylation disorder • Mitochondrial complex 1 deficiency, nuclear type 21 • Mitochondrial complex I deficiency, nuclear type 1	Likely pathogenic (Mar 26, 2024)
14-31561443-G-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Dec 18, 2023)
14-31561456-G-A		Inborn genetic diseases	Uncertain significance (Nov 22, 2022)
14-31561464-C-T		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
14-31561474-G-A			Uncertain significance (May 05, 2021)
14-31561485-C-T		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
14-31561500-G-A		Inborn genetic diseases	Uncertain significance (Apr 26, 2023)
14-31561510-C-T		Mitochondrial complex I deficiency, nuclear type 1	Conflicting classifications of pathogenicity (May 01, 2022)
14-31561513-T-C			Uncertain significance (Aug 08, 2022)
14-31561516-G-T		Mitochondrial complex I deficiency, nuclear type 1 • not specified • NUBPL-related disorder	Conflicting classifications of pathogenicity (Dec 28, 2023)
14-31561525-G-A			Uncertain significance (Dec 02, 2021)
14-31561529-G-A		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Mar 16, 2018)
14-31561544-C-A			Likely benign (Oct 27, 2022)
14-31561554-G-A			Likely benign (Aug 07, 2023)
14-31561561-C-T			Likely benign (Oct 24, 2020)
14-31561764-G-C			Likely benign (Aug 03, 2018)
14-31561965-G-A			Likely benign (Aug 30, 2018)
14-31562039-C-T			Benign (Jul 07, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NUBPL	protein_coding	protein_coding	ENST00000281081	11	371269

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000107	0.947	124757	0	37	124794	0.000148

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.285	160	170	0.939	0.00000842	2037
Missense in Polyphen		46	68.199	0.67449		764
Synonymous	1.07	51	61.6	0.827	0.00000345	635
Loss of Function	1.80	11	19.6	0.561	9.85e-7	222

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000655	0.0000646
Ashkenazi Jewish	0.000199	0.000199
East Asian	0.000223	0.000223
Finnish	0.00	0.00
European (Non-Finnish)	0.000239	0.000238
Middle Eastern	0.000223	0.000223
South Asian	0.0000983	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I). May deliver of one or more Fe-S clusters to complex I subunits. {ECO:0000269|PubMed:19752196}.
• Pathway: EMT transition in Colorectal Cancer;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: 0.0910

Intolerance Scores

• loftool: 0.704
• rvis_EVS: 0.44
• rvis_percentile_EVS: 77.7

Haploinsufficiency Scores

• pHI: 0.0440
• hipred: N
• hipred_score: 0.289
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.720

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nubpl
• 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); hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: iron-sulfur cluster assembly;mitochondrial respiratory chain complex I assembly;mitochondrion morphogenesis
• Cellular component: mitochondrion;mitochondrial matrix;plasma membrane
• Molecular function: ATP binding;metal ion binding;4 iron, 4 sulfur cluster binding