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NDUFV1

NADH:ubiquinone oxidoreductase core subunit V1
2 disorders 1 causative 1 no genetic record 11q13.2 gene with protein product
HGNC:7716MonarchNCBI Gene 4723ENSG00000167792UniProt P49821OMIM 161015

Aliases: CI-51K.

Normal function · from ai-gene-review (P49821, commit 79fe13b38970) · AI-generated, not KB evidence

NDUFV1 encodes the 51 kDa flavoprotein subunit of mitochondrial NADH:ubiquinone oxidoreductase (Complex I, EC 7.1.1.2). It is a core catalytic subunit located in the N-module at the matrix-facing tip of the peripheral (hydrophilic) arm. NDUFV1 contains the FMN cofactor that serves as the primary electron acceptor from NADH, initiating electron transfer through a chain of iron-sulfur clusters toward ubiquinone. NDUFV1 also harbors one [4Fe-4S] cluster (N3) that participates in the electron relay. The reduced FMN site is also the predominant source of reactive oxygen species (superoxide/H2O2) produced by Complex I. NDUFV1 is part of the flavoprotein (FP) subcomplex together with NDUFV2 and NDUFV3. Biallelic mutations in NDUFV1 cause mitochondrial Complex I deficiency, nuclear type 4 (MC1DN4), typically presenting as Leigh syndrome with leukodystrophy, myoclonic epilepsy, and progressive neurodegeneration.

NDUFV1 is the catalytic flavoprotein subunit of mitochondrial NADH:ubiquinone oxidoreductase (Complex I) and the entry point of respiratory electron flow. It binds one non-covalently bound FMN cofactor and one [4Fe-4S] cluster (N3), both resolved in the human Complex I cryo-EM structure. NADH is oxidised by hydride transfer to the FMN in NDUFV1, and the reduced flavin then passes electrons one at a time to the N3 cluster held by Cys379/Cys382/Cys385/Cys425 within the same subunit, from there to the cluster chain of NDUFS1, and on toward the terminal N2 cluster at the quinone site — the subunit-level activity is therefore electron transfer, while the ubiquinone-terminal NADH dehydrogenase (ubiquinone) activity (GO:0008137) is a property of the whole holoenzyme to which NDUFV1 contributes. Because the flavin sits at the top of this wire, it is the predominant site of superoxide production by complex I when the downstream chain is blocked or the NADH/NAD+ ratio is high. NDUFV1 occupies the N-module at the matrix-facing tip of the peripheral arm of Complex I (GO:0045271), embedded in the inner mitochondrial membrane (GO:0005743). FMN binding (GO:0010181), NAD binding (GO:0051287), and [4Fe-4S] cluster binding (GO:0051539) are core cofactor-binding functions essential for this activity.
molecular function: electron transfer activity · contributes to molecular function: NADH dehydrogenase (ubiquinone) activity · directly involved in: mitochondrial electron transport, NADH to ubiquinone · locations: mitochondrial inner membrane · in complex: respiratory chain complex I
In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

DisorderRelationshipWhere the gene appears
Leigh Syndrome causative germline
CLINGEN: definitive
mechanism: Complex I deficiency
Mitochondrial Complex I Deficiency, Nuclear Type 13 no genetic record
mechanism: Failure of Complex I N-Module Assembly
ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen diseaseMOIClassificationdismech entry
Leigh syndrome MONDO:0009723 AR Definitive
2019-11-26
Leigh Syndrome causative
mitochondrial disease MONDO:0044970 AR Definitive
2024-05-20
 no dismech entry

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.