CBS

Chr 21AR

cystathionine beta-synthase

Also known as: HIP4

NCBI Gene: 875ENSG00000160200UniProt: P35520OMIM: 613381

The protein encoded by this gene acts as a homotetramer to catalyze the conversion of homocysteine to cystathionine, the first step in the transsulfuration pathway. The encoded protein is allosterically activated by adenosyl-methionine and uses pyridoxal phosphate as a cofactor. Defects in this gene can cause cystathionine beta-synthase deficiency (CBSD), which can lead to homocystinuria. This gene is a major contributor to cellular hydrogen sulfide production. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2016]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Homocystinuria, B6-responsive and nonresponsive typesMIM #236200
AR
Thrombosis, hyperhomocysteinemicMIM #236200
AR
UniProtCystathionine beta-synthase deficiency

Clinical highlights

Gene-disease validity (ClinGen)
classic homocystinuria · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
9
Active trials
1148
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.73
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — CBS
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.73LOEUF
pLI 0.000
Z-score 2.64
OE 0.45 (0.29–0.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.83Z-score
OE missense 0.87 (0.79–0.96)
301 obs / 344.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.45 (0.29–0.73)
0≤0.351.4
Missense OE?0.87 (0.79–0.96)
0≤0.61.4
Synonymous OE?1.11
0≤1.21.6
LoF obs/exp: 12 / 26.7Missense obs/exp: 301 / 344.4Syn Z: -1.11

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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
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
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)
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
Homocystinuria

Pegtibatinase as a Treatment for Patients With Classical Homocystinuria (HCU) (Also Known as the COMPOSE Study)

RECRUITING
NCT03406611Phase PHASE1, PHASE2Travere Therapeutics, Inc.Started 2019-01-22
PegtibatinasePlacebo
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
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
ALS

Amyotrophic Lateral Sclerosis (ALS) Families Project

RECRUITING
NCT03865420Columbia UniversityStarted 2018-09-11

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients