FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: homocystinuria due to cystathionine beta-synthase deficiency
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General Information
Name
homocystinuria due to cystathionine beta-synthase deficiency
FlyBase ID
FBhh0001469
Disease Ontology Term
Parent Disease
OMIM
HOMOCYSTINURIA DUE TO CYSTATHIONINE BETA-SYNTHASE DEFICIENCY
Overview

This report describes homocystinuria due to cystathionine beta-synthase deficiency, an automosomal recessive metabolic disorder of sulfer metabolism. The human gene implicated in this disease is CBS, an enzyme which catalyzes the first irreversible step of the transsulfuration pathway. There is a single orthologous gene in Drosophila, Dmel\Cbs, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

The human gene CBS gene has not been introduced into flies.

Amorphic and loss-of-function mutations of Dmel\Cbs are viable when homozygous. Abnormal learning and abnormal memory phenotypes are observed.

[updated Sept. 2022 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: homocystinuria due to cystathionine beta-synthase deficiency
OMIM report

[HOMOCYSTINURIA DUE TO CYSTATHIONINE BETA-SYNTHASE DEFICIENCY](https://omim.org/entry/236200)

Human gene(s) implicated

[CYSTATHIONINE BETA-SYNTHASE; CBS](https://omim.org/entry/613381)

Symptoms and phenotype

Classic homocystinuria is an autosomal recessive metabolic disorder of sulfur metabolism. The clinical features of untreated homocystinuria due to CBS deficiency usually manifest in the first or second decade of life and include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome (MIM:154700), and thromboembolic events. Light skin and hair can also be present. Biochemical features include increased urinary homocystine and methionine (summary by Reish et al. 1995; pubmed:7611281; Testai and Gorelick, 2010; pubmed:20142522). [from MIM:236200; 2022.09.01]

(OMIM, 2013-)
Genetics

Homocystinuria due to cystathionine beta-synthase deficiency is caused by homozygous or compound heterozygous mutation in the CBS gene on chromosome 21q22. [from MIM:613381; 2022.09.01]

(OMIM, 2013-)
Cellular phenotype and pathology
Molecular information

CBS catalyzes the the first irreversible step of transsulfuration. The enzyme conjugates homocysteine and serine to form cystathionine, which is subsequently converted into cysteine and alpha-ketobutyrate (Kraus et al., 1993; pubmed:7903580; Shan et al., 2001; pubmed:11230183). [from MIM:613381; 2022.09.01]

(OMIM, 2013-)
External links
Disease synonyms
CBS deficiency
classic homocystinuria
cystathionine beta synthase deficiency
cystathionine synthase deficiency
homocysteinemia
homocystinuria due to cystathionine beta-synthase deficiencyv
homocystinuria with or without response to pyridoxine
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    Symbol / Name
    CBS; cystathionine beta-synthase
    D. melanogaster ortholog (based on DIOPT)
    Dmel\Cbs
    (DIOPT, 2013-)
    Comments on ortholog(s)

    One to one: human gene to Drosophila gene.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Dmel\Cbs
      Gene Snapshot
      Cystathionine β-synthase (Cbs) encodes a cytosolic pyridoxal 5'-phosphate-dependent enzyme that catalyzes the condensation of L-homocysteine and L-serine to form L,L-cystathionine as part of L-cysteine biosynthesis (also known as the transsulfuration pathway). [Date last reviewed: 2026-02-19]
      Molecular function (GO)
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human CBS (1 Drosophila to 1 human).

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      H. sapiens (Human)
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (0 groups)
        Alleles Reported to Model Human Disease (Disease Ontology) (3 alleles)
        Cbs
        Models Based on Experimental Evidence ( 3 )
        Modifiers Based on Experimental Evidence ( 0 )
        Allele
        Disease
        Interaction
        References
        Alleles Representing Disease-Implicated Variants
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Related mammalian, viral, bacterial, or synthetic transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        CbsGD9407
        P{GD9407}
        w1118 P{GD9407}v32946
        CbsKK109084
        P{KK109084}
        P{KK109084}VIE-260B
        CbsHMS03028
        P{TRiP.HMS03028}
        y1 sc* v1 sev21; P{TRiP.HMS03028}attP2
        CbsNIG.1753R
        P{NIG.1753R}
        P{NIG.1753R}3
        CbsGL01309
        P{TRiP.GL01309}
        y1 sc* v1 sev21; P{TRiP.GL01309}attP40
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        Cbs5
        amorphic allele - molecular evidence
        CRISPR/Cas9
        Cbs8
        amorphic allele - molecular evidence
        CRISPR/Cas9
        References (5)