NFS1

NFS1 cysteine desulfurase, the group of Mitochondrial iron-sulfur assembly components

Basic information

Region (hg38): 20:35668052-35699355

Links

ENSG00000244005

∙ NCBI:9054 ∙ OMIM:603485 ∙ HGNC:15910 ∙ Uniprot:Q9Y697 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency (Supportive), mode of inheritance: AR
combined oxidative phosphorylation deficiency 52 (Strong), mode of inheritance: AR
combined oxidative phosphorylation deficiency 52 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 52	AR	Biochemical	The condition can involve severe, early-onset sequelae, and mitochondrial cofactor therapy has been described as resulting in clinical improvement	Biochemical; Cardiovascular; Neurologic	24498631; 33457206

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NFS1 gene.

not_specified (71 variants)
not_provided (70 variants)
NFS1-related_disorder (6 variants)
Combined_oxidative_phosphorylation_deficiency_52 (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021100.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				22 clinvar	1 clinvar	23
missense		1 clinvar	66 clinvar	3 clinvar		70
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	68	25	1

Highest pathogenic variant AF is 0.00006457445

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NFS1	protein_coding	protein_coding	ENST00000374092	13	31305

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0554	0.945	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.41	196	260	0.754	0.0000145	2923
Missense in Polyphen		57	100.93	0.56473		1117
Synonymous	0.233	85	87.8	0.968	0.00000410	941
Loss of Function	3.32	7	24.8	0.282	0.00000129	287

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000153	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000972	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the removal of elemental sulfur from cysteine to produce alanine. It supplies the inorganic sulfur for iron- sulfur (Fe-S) clusters. May be involved in the biosynthesis of molybdenum cofactor. {ECO:0000269|PubMed:18650437}.;
Pathway: Sulfur relay system - Homo sapiens (human);Thiamine metabolism - Homo sapiens (human);[2Fe-2S] iron-sulfur cluster biosynthesis;Mitochondrial iron-sulfur cluster biogenesis;Metabolism;Molybdenum cofactor biosynthesis;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;molybdenum cofactor biosynthesis (Consensus)

Recessive Scores

pRec: 0.380

Intolerance Scores

loftool: 0.110
rvis_EVS: -0.43
rvis_percentile_EVS: 25.37

Haploinsufficiency Scores

pHI: 0.118
hipred: Y
hipred_score: 0.598
ghis: 0.642

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Nfs1
Phenotype

Gene ontology

Biological process: sulfur amino acid metabolic process;Mo-molybdopterin cofactor biosynthetic process;iron incorporation into metallo-sulfur cluster;molybdopterin cofactor biosynthetic process;small molecule metabolic process;[2Fe-2S] cluster assembly;protein-containing complex assembly
Cellular component: nucleus;nucleoplasm;mitochondrion;mitochondrial matrix;cytosol
Molecular function: protein binding;pyridoxal phosphate binding;cysteine desulfurase activity;protein homodimerization activity;metal ion binding;iron-sulfur cluster binding