CBS

Chr 21AR

cystathionine beta-synthase

The encoded protein functions as a homotetramer that catalyzes the conversion of homocysteine to cystathionine in the transsulfuration pathway, using pyridoxal phosphate as a cofactor and activated by adenosyl-methionine. Mutations cause autosomal recessive cystathionine beta-synthase deficiency leading to homocystinuria (both B6-responsive and nonresponsive types) and hyperhomocysteinemic thrombosis. The pathogenic mechanism involves loss of enzymatic function resulting in toxic accumulation of homocysteine.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.732 OMIM phenotypes
Clinical SummaryCBS
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Gene-Disease Validity (ClinGen)
classic homocystinuria · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.73LOEUF
pLI 0.000
Z-score 2.64
OE 0.45 (0.290.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.83Z-score
OE missense 0.87 (0.790.96)
301 obs / 344.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.290.73)
00.351.4
Missense OE0.87 (0.790.96)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 12 / 26.7Missense obs/exp: 301 / 344.4Syn Z: -1.11
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCBS-related homocystinuria due to cystathionine beta-synthase deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.75top 25%
GOF
0.6542th %ile
LOF
0.2582th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CBS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

PSPPSP - Progressive Supranuclear PalsyCorticobasal Syndrome

The CurePSP Genetics Program

RECRUITING
NCT06647641Massachusetts General HospitalStarted 2024-10-08
Whole genome sequencing will be performed at the NIH
Obesity and OverweightPre-diabeticType 2 Diabetes Mellitus (T2DM)

Targeted Precision Nutrition Strategy To Prevent Chronic Metabolic Diseases

RECRUITING
NCT06923644Phase NAMaastricht University Medical CenterStarted 2025-04-23
Optimal Metabotype-specific dietSub-optimal diet
SepsisARDSCritical Illness

Early Severe Illness TrAnslational BioLogy InformaticS in Humans

RECRUITING
NCT05591924London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sStarted 2024-04-26
PhelebotomyBroncheoalveolar LavageTracheal Aspirate
ALS

Amyotrophic Lateral Sclerosis (ALS) Families Project

RECRUITING
NCT03865420Columbia UniversityStarted 2018-09-11
Progressive Supranuclear PalsyMultiple System AtrophyCorticobasal Syndrome

The NADAPT Study: a Randomized Double-blind Trial of NAD Replenishment Therapy for Atypical Parkinsonism

RECRUITING
NCT06162013Phase PHASE2Haukeland University HospitalStarted 2024-03-05
Nicotinamide RibosidePlacebo
Amyotrophic Lateral Sclerosis

Personalized Antisense Oligonucleotide Therapy for A Single Patient With CHCHD10 ALS (nL18576)

NOT YET RECRUITING
NCT07423494Phase PHASE1, PHASE2n-Lorem FoundationStarted 2026-03
nL-CHCHD-001
ALSFTDALS (Amyotrophic Lateral Sclerosis)Frontal Temporal Dementia (FTD)

Effects of Probiotics in Amyotrophic Lateral Sclerosis-Frontotemporal Dementia Spectrum Disorder (ALS-FTDSD) Patients

RECRUITING
NCT06051123Phase NACentre hospitalier de l'Université de Montréal (CHUM)Started 2024-01-01
ProbioticPlacebo
Neurodegenerative DiseaseBehavioral Variant Frontotemporal Dementia (bvFTD)Primary Progressive Aphasia(PPA)

Tracking and Predicting How Brain Damage Spreads in Neurodegenerative Diseases

ENROLLING BY INVITATION
NCT07567664Phase NAIRCCS San RaffaeleStarted 2017-06-01
3 Tesla MRI without contrast mediumBlood sample for genetic analysisCerebrospinal fluid sampling (CSF)
Clinical Literature
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