NFS1

Chr 20q11.22

NFS1 cysteine desulfurase

Aliases:: NifS, IscS
MANE:: ENST00000374092.9

OMIM: 603485 ↗NCBI: 9054 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

NFS1 · Q9Y697

v62025-08-01

Predicted Aligned Error matrix for NFS1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

88.8/ 100

Confident

457 residues

Confidence breakdown

Very high(≥ 90)81%
Confident(70–90)5%
Low(50–70)2%
Very low(< 50)13%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Likely inborn error of metabolism
BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders
BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

combined oxidative phosphorylation deficiency 52
0.54
neurodegenerative disease
0.47
severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency
0.37
coronary artery disorder
0.16
placenta praevia
0.16
skin neoplasm
0.16
placental retention
0.16
neoplasm
0.09
gastric cancer
0.09
colorectal carcinoma
0.09

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Cysteine desulfurase

Cysteine desulfurase, of the core iron-sulfur cluster (ISC) assembly complex, that catalyzes the desulfuration of L-cysteine to L-alanine, as component of the cysteine desulfurase complex, leading to the formation of a cysteine persulfide intermediate at the active site cysteine residue and participates in the [2Fe-2S] clusters assembly on the scaffolding protein ISCU (PubMed:18650437, PubMed:29097656, PubMed:31101807). The persulfide is then transferred on the flexible Cys loop from the catalytic site of NFS1 to the surface of NFS1 (PubMed:29097656). After the NFS1-linked persulfide sulfur is transferred to one of the conserved Cys residues of the scaffold, a reaction assisted by FXN (By similarity). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity)