CPS1

Chr 2AR

carbamoyl-phosphate synthase 1

Also known as: CPS1D, CPSASE1, GATD6, PHN

This gene encodes carbamoyl phosphate synthetase I, a mitochondrial enzyme that catalyzes the synthesis of carbamoyl phosphate from ammonia and bicarbonate in the first committed step of the urea cycle. Mutations cause carbamoyl phosphate synthetase I deficiency, an autosomal recessive disorder that impairs the body's ability to remove excess ammonia. The pathogenic mechanism involves loss of enzyme function leading to hyperammonemia.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.521 OMIM phenotype
Clinical SummaryCPS1
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Gene-Disease Validity (ClinGen)
carbamoyl phosphate synthetase I deficiency disease · 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
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.000
Z-score 5.08
OE 0.38 (0.280.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.46Z-score
OE missense 0.85 (0.800.91)
681 obs / 797.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.280.52)
00.351.4
Missense OE0.85 (0.800.91)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 30 / 78.7Missense obs/exp: 681 / 797.0Syn Z: -1.29
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCPS1-related carbamoyl phosphate synthetase 1 deficiencyLOFAR

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

DN
0.7228th %ile
GOF
0.5857th %ile
LOF
0.3163th %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

CPS1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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