NFU1

NFU1 iron-sulfur cluster scaffold, the group of Mitochondrial iron-sulfur assembly components

Basic information

Region (hg38): 2:69396113-69437628

Previous symbols: [ "HIRIP5" ]

Links

ENSG00000169599 ∙ NCBI:27247 ∙ OMIM:608100 ∙ HGNC:16287 ∙ Uniprot:Q9UMS0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple mitochondrial dysfunctions syndrome 1 (Definitive), mode of inheritance: AR
• multiple mitochondrial dysfunctions syndrome 1 (Strong), mode of inheritance: AR
• multiple mitochondrial dysfunctions syndrome 1 (Supportive), mode of inheritance: AR
• multiple mitochondrial dysfunctions syndrome 1 (Strong), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple mitochondrial dysfunctions syndrome 1	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; Musculoskeletal; Neurologic	11156534; 21944046

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NFU1 gene.

• Multiple mitochondrial dysfunctions syndrome 1 (3 variants)
• not provided (2 variants)
• NFU1-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFU1 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			1	13	1	15
missense	2	2	39		2	45
nonsense			1			1
start loss					1	1
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2	1			3
splice region	1		5	13		19
non coding			6	31	22	59
Total	2	4	49	44	26

Highest pathogenic variant AF is 0.000118

Variants in NFU1

This is a list of pathogenic ClinVar variants found in the NFU1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-69396143-C-T		Multiple mitochondrial dysfunctions syndrome 1	Uncertain significance (Jan 13, 2018)
2-69396278-C-T		Multiple mitochondrial dysfunctions syndrome 1	Uncertain significance (Aug 10, 2023)
2-69396284-C-T		Inborn genetic diseases	Uncertain significance (Jun 16, 2024)
2-69396290-C-G		SPASTIC PARAPLEGIA 93, AUTOSOMAL RECESSIVE	Pathogenic (Sep 09, 2024)
2-69396291-C-T		not specified	Uncertain significance (Mar 22, 2023)
2-69396298-C-G		Multiple mitochondrial dysfunctions syndrome 1	Likely benign (May 15, 2023)
2-69396298-C-CA		not specified	Likely benign (Oct 02, 2015)
2-69400360-A-T		Multiple mitochondrial dysfunctions syndrome 1	Uncertain significance (Nov 10, 2021)
2-69400376-T-C		Multiple mitochondrial dysfunctions syndrome 1	Likely benign (Oct 05, 2023)
2-69400382-C-T		Multiple mitochondrial dysfunctions syndrome 1	Conflicting classifications of pathogenicity (Jun 10, 2023)
2-69400385-C-T		Multiple mitochondrial dysfunctions syndrome 1	Benign/Likely benign (Apr 29, 2022)
2-69400386-G-A		Multiple mitochondrial dysfunctions syndrome 1	Uncertain significance (Aug 27, 2021)
2-69400387-G-T		Multiple mitochondrial dysfunctions syndrome 1	Uncertain significance (Feb 18, 2022)
2-69400408-T-C		Multiple mitochondrial dysfunctions syndrome 1 • not specified	Conflicting classifications of pathogenicity (Jun 23, 2023)
2-69400448-G-C		Multiple mitochondrial dysfunctions syndrome 1	Uncertain significance (Aug 16, 2022)
2-69400455-C-A		Multiple mitochondrial dysfunctions syndrome 1 • SPASTIC PARAPLEGIA 93, AUTOSOMAL RECESSIVE	Conflicting classifications of pathogenicity (Jul 24, 2024)
2-69400462-C-A		Multiple mitochondrial dysfunctions syndrome 1 • NFU1-related disorder	Pathogenic (Dec 11, 2023)
2-69400503-T-C		Multiple mitochondrial dysfunctions syndrome 1	Uncertain significance (Jun 20, 2023)
2-69400519-C-T		Multiple mitochondrial dysfunctions syndrome 1 • SPASTIC PARAPLEGIA 93, AUTOSOMAL RECESSIVE	Likely pathogenic (Dec 02, 2020)
2-69400536-G-C		SPASTIC PARAPLEGIA 93, AUTOSOMAL RECESSIVE	Uncertain significance (Nov 26, 2019)
2-69400538-C-T		Multiple mitochondrial dysfunctions syndrome 1	Uncertain significance (Apr 20, 2022)
2-69400543-G-A		NFU1-related disorder	Likely benign (Apr 03, 2020)
2-69400554-A-C		Multiple mitochondrial dysfunctions syndrome 1	Likely benign (Oct 17, 2023)
2-69400554-A-G		Multiple mitochondrial dysfunctions syndrome 1	Likely benign (Aug 23, 2022)
2-69400590-T-C			Likely benign (Jun 05, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NFU1	protein_coding	protein_coding	ENST00000410022	8	41879

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000415	0.626	125704	0	43	125747	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.370	123	135	0.910	0.00000623	1653
Missense in Polyphen		40	45.843	0.87254		604
Synonymous	0.598	42	47.2	0.889	0.00000222	473
Loss of Function	0.940	10	13.8	0.727	5.80e-7	172

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000938	0.000912
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000133	0.000123
Middle Eastern	0.0000544	0.0000544
South Asian	0.000261	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Iron-sulfur cluster scaffold protein which can assemble [4Fe-4S] clusters and deliver them to target proteins. {ECO:0000269|PubMed:12886008, ECO:0000269|PubMed:27818104, ECO:0000269|PubMed:28906594}.
• Disease: DISEASE: Multiple mitochondrial dysfunctions syndrome 1 (MMDS1) [MIM:605711]: A severe disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, hyperglycinemia and early death. Some patients show failure to thrive, pulmonary hypertension, hypotonia and irritability. Biochemical features include severe combined deficiency of the 2-oxoacid dehydrogenases, defective lipoic acid synthesis and reduction in activity of mitochondrial respiratory chain complexes. {ECO:0000269|PubMed:21944046, ECO:0000269|PubMed:22077971, ECO:0000269|PubMed:25918518, ECO:0000269|PubMed:28161430, ECO:0000269|PubMed:28906594}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.144

Intolerance Scores

• loftool: 0.621
• rvis_EVS: 0.42
• rvis_percentile_EVS: 76.81

Haploinsufficiency Scores

• pHI: 0.569
• hipred: Y
• hipred_score: 0.562
• ghis: 0.455

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.900

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nfu1

Gene ontology

• Biological process: iron-sulfur cluster assembly;protein maturation by iron-sulfur cluster transfer
• Cellular component: nucleus;nucleoplasm;mitochondrion;cytosol
• Molecular function: iron ion binding;protein binding;4 iron, 4 sulfur cluster binding