FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
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Marygold, S.J. (2018.6.26). D. melanogaster Had (beta Hydroxy acid dehydrogenase) genes. 
FlyBase ID
FBrf0239280
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Personal communication to FlyBase
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Borack and Sofer, 1971 (FBrf0022880), Borack, 1972 (FBrf0023693) and Tobler and Grell, 1978 (FBrf0031064) characterize a "beta-L-hydroxy acid dehydrogenase" activity (EC:1.1.1.45) in D. melanogaster that, through to FB2018_03, was associated with the uncloned 'Had' gene 'Had' (FBgn0001172).  Findings from these papers include that: (i) the substrates of the enzyme include L-beta-hydroxybutyrate and L-gulonic acid; (ii) the enzyme likely exists as a dimer, with molecular weight of 63kD; (iii) the activity localizes predominantly to malpighian tubules; (iv) the gene maps by recombination to position 54.4 on the X chromosome; (v) an enzymatic null mutant shows no apparent phenotype.
The Gene Ontology term for this enzymatic activity is "L-gulonate 3-dehydrogenase activity (GO:0050104)". There are no sequenced-localized (ie. CG) fly genes annotated with this term, but a single human gene does have this annotation: CRYL1 (crystallin lambda 1), aka "GDH" and "L-gulonate 3-dehydrogenase” (see PMID:15809331).  The DIOPT orthology tool (v7) predicts 2 fly orthologs of this human gene:
CG10131 - DIOPT score 12/15, aa identity 47%, aa similarity 67%
CG9914 - DIOPT score 15/15, aa identity 52%, aa similarity 71%
CG10131 (FBgn0033949) cannot equate to 'Had' as it maps to the 2nd chromosome (2-72 - 2-76) and its major expression is in larval carcass, larval fat body, adult head, adult heart.
But CG9914 (FBgn0030737) matches the description of 'Had' in almost every regard:
- maps to the X chromosome, 1-53 - 1-54.5
- predicted molecular weight of 35kD (around half of the reported MW of the dimer)
- major expression is larval and adult malpighian tubules
- Knockdown by transgenic RNAi using 4 different GAL4 drivers results in viable flies
Looking at the InterPro signatures associated with CG9914, four are diagnostic of 2-3 Dmel genes:
- 3-hydroxyacyl-CoA dehydrogenase (IPR022694) => 3 genes: CG9914, CG10131, Mtpalpha
- 3-hydroxyacyl-CoA dehydrogenase, C-terminal (IPR006108) => 3 genes: CG9914, CG10131, Mtpalpha
- 3-hydroxyacyl-CoA dehydrogenase, NAD binding (IPR006176) => 3 genes: CG9914, CG10131, Mtpalpha
- 3-hydroxyacyl-CoA dehydrogenase, conserved site (IPR006180) => 2 genes: CG9914, CG10131
Based on the above analysis, the gene reports for CG9914 and 'Had' should be merged, with the final gene being named 'Had1'.  CG10131 should then be named 'Had2'.
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    English
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    Gene Groups (1)
    Genes (3)