CTH

Chr 1AR

cystathionine gamma-lyase

Also known as: CGL, CSE

NCBI Gene: 1491ENSG00000116761UniProt: Q96IQ7

This gene encodes cystathionine gamma-lyase, a cytoplasmic enzyme in the trans-sulfuration pathway that converts cystathionine to cysteine, which is essential for hepatic glutathione synthesis. Mutations cause cystathioninuria, inherited in an autosomal recessive pattern. The gene shows minimal constraint against loss-of-function variants (pLI near 0, LOEUF 0.96), consistent with the typically benign nature of cystathioninuria.

Summary from RefSeq, OMIM
Research Assistant →

Primary Disease Associations & Inheritance

CystathioninuriaMIM #219500
AR
1
Active trials
148
Pubs (1 yr)
28
P/LP submissions
4%
P/LP missense
0.96
LOEUF
DN
Mechanism· predicted
Clinical Summary— CTH
🧬
Gene-Disease Validity (ClinGen)
cystathioninuria · 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.
📋
ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 89 VUS of 143 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.96LOEUF
pLI 0.000
Z-score 1.72
OE 0.62 (0.41–0.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.41Z-score
OE missense 0.92 (0.82–1.03)
204 obs / 221.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.62 (0.41–0.96)
0≤0.351.4
Missense OE0.92 (0.82–1.03)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 15 / 24.1Missense obs/exp: 204 / 221.3Syn Z: 0.16
DN
0.7228th %ile
GOF
0.5563th %ile
LOF
0.3067th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

143 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic2
VUS89
Likely Benign11
Benign4
Conflicting3
24
Pathogenic
2
Likely Pathogenic
89
VUS
11
Likely Benign
4
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
22
0
24
Likely Pathogenic
1
0
1
0
2
VUS
1
54
32
2
89
Likely Benign
0
2
7
2
11
Benign
0
1
3
0
4
Conflicting
—3
Total358654133

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CTH · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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