NDUFB9 (Complex I-B22 / LYRM3) — review notes

UniProt: Q9Y6M9 (NDUB9_HUMAN). Gene: NDUFB9; synonyms LYRM3, UQOR22.
HGNC:7704. GeneID 4715. Chromosome 8 (8q13). 179 aa.

Identity and family

• RecName: "NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9";
  AltNames: Complex I-B22 / CI-B22; LYR motif-containing protein 3; NADH-ubiquinone
  oxidoreductase B22 subunit. [file:human/NDUFB9/NDUFB9-uniprot.txt lines 6-11]
• Belongs to the complex I LYR family. [file:human/NDUFB9/NDUFB9-uniprot.txt
  "Belongs to the complex I LYR family."]
• InterPro: Complex1_LYR domain (IPR008011), Complex1_LYR_NDUFB9_LYRM3 (IPR045292),
  NDUFB9 (IPR033034); Pfam PF05347; CDD cd20263. [file:human/NDUFB9/NDUFB9-uniprot.txt lines 312-318]

Function (core)

• Accessory (supernumerary) subunit of mitochondrial membrane respiratory chain
  NADH dehydrogenase (Complex I), believed to be NOT involved in catalysis.
  Complex I transfers electrons from NADH to the respiratory chain; the immediate
  electron acceptor is believed to be ubiquinone.
  [file:human/NDUFB9/NDUFB9-uniprot.txt "involved in catalysis. Complex I functions
  in the transfer of electrons"] (FUNCTION, ECO:0000269|PubMed:27626371)
• Non-catalytic → honest MF is structural molecule activity (GO:0005198),
  contributing to the complex-level NADH dehydrogenase (ubiquinone) activity
  (GO:0008137) via contributes_to_molecular_function, NOT a direct enables.

Complex membership

• Mammalian complex I is composed of 45 different subunits.
  [file:human/NDUFB9/NDUFB9-uniprot.txt "Mammalian complex I is composed of 45
  different subunits."] (SUBUNIT; ECO:0000269|PubMed:12611891, PubMed:27626371)
• Direct MS/immunopurification identification of NDUFB9 as a Complex I subunit:
  PMID:12611891 — resolved human
  homologues of 42 Complex I polypeptides.
• Systematic knockout / complexome study: accessory subunits integral for assembly
  and function; most "required for assembly of a functional complex and 1 subunit
  is essential for" cell viability; loss of a subunit destabilizes subunits of the
  same structural module. PMID:27626371
• Cryo-EM megacomplex I2III2IV2 gives "precise assignment of individual subunits of"
  human CI, placing NDUFB9 in the complex and respirasome. PMID:28844695
• part_of GO:0045271 (respiratory chain complex I) is the well-supported core CC:
  evidence IDA (PMID:12611891, PMID:27626371), IPI (PMID:28844695, ComplexPortal),
  IBA (GO_REF:0000033), IEA (Ensembl GO_REF:0000107), NAS (PMID:9878551).

Localization

• Subcellular: Mitochondrion inner membrane; Peripheral membrane protein; Matrix side.
  [file:human/NDUFB9/NDUFB9-uniprot.txt "Mitochondrion inner membrane"] (SUBCELLULAR
  LOCATION, ECO:0000305|PubMed:12611891)
• Supported by IDA (ComplexPortal PMID:28844695), TAS (Reactome; PMID:8661098),
  HPA IDA (mitochondrion), HTP (PMID:34800366).

Biological process

• Core BP: mitochondrial electron transport, NADH to ubiquinone (GO:0006120) —
  IEA/NAS/TAS; and Complex I assembly (GO:0032981). NDUFB9 participates via its
  structural contribution to the assembled complex.
• Complex I: "the transport of electrons from NADH to ubiquinone, which is"
  accompanied by proton translocation. PMID:9878551

Disease

• Mitochondrial complex I deficiency, nuclear type 24 (MC1DN24), MIM 618245,
  autosomal recessive; variant p.Leu64Pro. [file:human/NDUFB9/NDUFB9-uniprot.txt
  lines 186-199, 340-343] (ECO:0000269|PubMed:22200994)

Annotations judged over-broad / over-annotated (subunit-level)

• GO:0008137 "enables NADH dehydrogenase (ubiquinone) activity" (NAS PMID:9878551;
  TAS PMID:8661098): NDUFB9 is non-catalytic → MARK_AS_OVER_ANNOTATED; captured as
  contributes_to_molecular_function in core_functions instead of direct enables.
• GO:1902600 proton transmembrane transport (IEA GO_REF:0000108, derived from
  GO:0008137): over-annotation for an accessory subunit → MARK_AS_OVER_ANNOTATED.
• GO:0042776 proton-motive-force-driven mitochondrial ATP synthesis (NAS
  PMID:30030361): downstream OXPHOS outcome, performed by Complex V; over-broad for
  a Complex I accessory subunit → MARK_AS_OVER_ANNOTATED.
• GO:0007605 sensory perception of sound (TAS PMID:8661098): positional-candidate
  inference (NDUFB9 maps to 8q13 BOR region); "this gene should be considered a
  strong candidate for involvement in" hearing loss — not a demonstrated auditory
  function → MARK_AS_OVER_ANNOTATED.
• Bare GO:0005515 protein binding (7× IPI, large-scale interactome/HTT screens):
  retained per policy but MARK_AS_OVER_ANNOTATED; uninformative for MF.
• GO:0009060 aerobic respiration (NAS PMID:30030361): true at pathway level but
  broad/inherited → KEEP_AS_NON_CORE.
• GO:0005739 mitochondrion (IEA/IDA/HTP): correct but general vs inner membrane →
  KEEP_AS_NON_CORE.

Core functions chosen

• molecular_function: GO:0005198 (structural molecule activity)
• contributes_to_molecular_function: GO:0008137 (NADH dehydrogenase (ubiquinone) activity)
• directly_involved_in: GO:0006120, GO:0032981
• locations: GO:0005743 (mitochondrial inner membrane)
• in_complex: GO:0045271 (respiratory chain complex I)

Provenance note

• All cited publications in this review are abstract-only in the cache
  (full_text_available: false), except PMID:17500595 (full text; HTT interactome,
  supports IPI protein binding only). No paraphrase used in supporting_text; every
  quote is a verbatim single-line substring of the cited source.