NFU1 (NFU1 iron-sulfur cluster scaffold)

Gene

• Entrez ID: 27247
• Gene name: NFU1 iron-sulfur cluster scaffold
• Gene symbol: NFU1
• Synonyms (NCBI Gene): CGI-33, HIRIP, HIRIP5, MMDFS, MMDS1, NIFUC, Nfu, NifU, SPG93
• Chromosome: 2
• Chromosome location: 2p13.3
• Summary: This gene encodes a protein that is localized to mitochondria and plays a critical role in iron-sulfur cluster biogenesis. The encoded protein assembles and transfers 4Fe-4S clusters to target apoproteins including succinate dehydrogenase and lipoic acid

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs371546359	T>A	Pathogenic	Splice acceptor variant
rs374514431	C>A	Pathogenic	Non coding transcript variant, intron variant, coding sequence variant, missense variant
rs377381866	T>C	Likely-pathogenic	Intron variant, coding sequence variant, non coding transcript variant, missense variant
rs756085990	C>T	Pathogenic	Intron variant
rs1354126704	G>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1464338870	C>G,T	Likely-pathogenic	Splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT028517	hsa-miR-30a-5p	Proteomics	18668040
MIRT052291	hsa-let-7b-5p	CLASH	23622248
MIRT048651	hsa-miR-99a-5p	CLASH	23622248
MIRT2282557	hsa-miR-1297	CLIP-seq
MIRT2282558	hsa-miR-26a	CLIP-seq
MIRT2282559	hsa-miR-26b	CLIP-seq
MIRT2282560	hsa-miR-4310	CLIP-seq
MIRT2282561	hsa-miR-4326	CLIP-seq
MIRT2282562	hsa-miR-4465	CLIP-seq
MIRT2282563	hsa-miR-4477a	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005506	Function	Iron ion binding	IDA	12886008
GO:0005506	Function	Iron ion binding	IEA
GO:0005515	Function	Protein binding	IPI	11342215, 12915448, 22190034, 25416956, 26702583, 27532772, 32296183
GO:0005634	Component	Nucleus	IDA	12886008
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	12886008
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005829	Component	Cytosol	IDA	12886008, 12915448
GO:0005829	Component	Cytosol	IEA
GO:0016226	Process	Iron-sulfur cluster assembly	IDA	12886008, 28906594
GO:0016226	Process	Iron-sulfur cluster assembly	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0051536	Function	Iron-sulfur cluster binding	IEA
GO:0051537	Function	2 iron, 2 sulfur cluster binding	IDA	27538573
GO:0051539	Function	4 iron, 4 sulfur cluster binding	IBA
GO:0051539	Function	4 iron, 4 sulfur cluster binding	IDA	12886008, 28906594
GO:0051604	Process	Protein maturation	IBA
GO:0051604	Process	Protein maturation	IDA	27538573

Other IDs

• MIM: 608100
• HGNC: 16287
• e!Ensembl: ENSG00000169599

Protein

• UniProt ID: Q9UMS0
• Protein name: NFU1 iron-sulfur cluster scaffold homolog, mitochondrial (HIRA-interacting protein 5)
• Protein function: Iron-sulfur cluster scaffold protein which can assemble [4Fe-4S] clusters and deliver them to target proteins.
• PDB: 2LTM, 2M5O
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08712	Nfu_N	61 → 148	Scaffold protein Nfu/NifU N terminal	Domain
  PF01106	NifU	173 → 239	NifU-like domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitous. Expression in adult lung is weak compared to fetal lung. {ECO:0000269|PubMed:12915448}.
• Sequence:

  MAATARRGWGAAAVAAGLRRRFCHMLKNPYTIKKQPLHQFVQRPLFPLPAAFYHPVRYMF
  IQTQDTPNPNSLKFIPGKPVLETRTMDFPTPAAAFRSPLARQLFRIEGVKSVFFGPDFIT
  VTKENEELDWNLLKPDIYATIMDFFASGLPLVTEETPSGEAGSEEDDEVVAMIKELLDTR
  IRPTVQEDGGDVIYKGFEDGIVQLKLQGSCTSCPSSIITLKNGIQNMLQFYIPEVEGVEQ
  VMDDESDEKEANSP

• Sequence length: 254

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Familial cancer of breast	Pathogenic	rs756085990	RCV005898545	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Multiple mitochondrial dysfunctions syndrome 1	Likely pathogenic; Pathogenic	rs1281276965, rs2104735490, rs371546359, rs374514431, rs756085990, rs1354126704, rs1464338870	RCV001333595 RCV001706832 RCV001706833 RCV002517248 RCV000023678 RCV000578252 RCV000578338 RCV000991363	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NFU1-related disorder	Likely pathogenic; Pathogenic	rs1281276965, rs374514431	RCV004756211 RCV003415735	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spastic paraplegia 93, autosomal recessive	Likely pathogenic; Pathogenic	rs1281276965, rs2104735490	RCV006252779 RCV004699444	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Uterine corpus endometrial carcinoma	Likely pathogenic; Pathogenic	rs1281276965	RCV005911103	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Fatal multiple mitochondrial dysfunctions syndrome	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASE	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POST-OPERATIVE ACUTE KIDNEY INJURY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Brain Diseases	Brain disease	Pubtator	25758857	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	36385109	Associate	★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognition disorder	Pubtator	25758857	Associate	★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	23179554, 25758857, 26688339		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypersensitivity Delayed	Hypersensitivity	Pubtator	36256512	Associate	★☆☆☆☆ Found in Text Mining only
Hypertension Pulmonary	Pulmonary hypertension	Pubtator	22077971	Associate	★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	31461310		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Idiopathic pulmonary arterial hypertension	Pulmonary arterial hypertension	BEFREE	31461310		★☆☆☆☆ Found in Text Mining only
Idiopathic pulmonary arterial hypertension	Pulmonary arterial hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lafora Disease	Lafora Disease	BEFREE	12915448		★☆☆☆☆ Found in Text Mining only
Leukodystrophy	Leukodystrophy	BEFREE	28470589		★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy	Leukoencephalopathy	BEFREE	24462778, 25758857		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	22077971, 27381105		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial disease	Pubtator	22077971, 37823603	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Myopathies	Mitochondrial myopathy	BEFREE	24573684		★☆☆☆☆ Found in Text Mining only
Multiple Mitochondrial Dysfunctions Syndrome	Multiple Mitochondrial Dysfunctions Syndrome	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 1	Multiple Mitochondrial Dysfunctions Syndrome	GENOMICS_ENGLAND_DG	11156534, 27604308		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 1	Multiple Mitochondrial Dysfunctions Syndrome	UNIPROT_DG	21944046, 22077971, 25918518, 28161430, 28906594		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 1	Multiple Mitochondrial Dysfunctions Syndrome	ORPHANET_DG	24334290, 24777537		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 1	Multiple Mitochondrial Dysfunctions Syndrome	BEFREE	28161430, 28470589, 28906594, 29767723		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 1	Multiple Mitochondrial Dysfunctions Syndrome	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Multiple mitochondrial dysfunctions syndrome type 1	Multiple Mitochondrial Dysfunctions Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	BEFREE	18304497		★☆☆☆☆ Found in Text Mining only
Paraparesis Spastic	Paraparesis	Pubtator	25758857	Associate	★☆☆☆☆ Found in Text Mining only
Paraplegia	Paraplegia	Pubtator	25758857	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Peripheral nervous system disease	Pubtator	25758857	Associate	★☆☆☆☆ Found in Text Mining only
Pheochromocytoma	Pheochromocytoma	Pubtator	33397043	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary arterial hypertension	Pulmonary arterial hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sjogren's Syndrome	Sjogren syndrome	Pubtator	37984252	Associate	★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia	Spastic Paraplegia	BEFREE	25758857		★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia Hereditary	Hereditary spastic paraplegia	Pubtator	36256512	Associate	★☆☆☆☆ Found in Text Mining only