OTC

Chr XX-linked

ornithine transcarbamylase

Also known as: OCTD, OTC1, OTCD, OTCase

NCBI Gene: 5009 ENSG00000036473 UniProt: P00480

This nuclear gene encodes a mitochondrial matrix enzyme. The encoded protein is involved in the urea cycle which functions to detoxify ammonia into urea for excretion. Mutations in this enzyme lead to ornithine transcarbamylase deficiency, which causes hyperammonemia. [provided by RefSeq, May 2022]

Primary Disease Associations & Inheritance

Ornithine transcarbamylase deficiencyMIM #311250

X-linked

UniProtOrnithine carbamoyltransferase deficiency

278

ClinVar variants

Pathogenic / LP

0.87

pLI score

Active trials

Clinical Summary— OTC

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Gene-Disease Validity (ClinGen)

ornithine carbamoyltransferase deficiency · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.

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ClinVar Variants

47 Pathogenic / Likely Pathogenic· 120 VUS of 278 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.41LOEUF

pLI 0.873

Z-score 3.18

OE 0.13 (0.05–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.33Z-score

OE missense 0.67 (0.57–0.81)

89 obs / 131.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.05–0.41)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.57–0.81)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	2	19	0	24
Likely Pathogenic	5	14	4	0	23
VUS	1	100	18	1	120
Likely Benign	0	1	60	36	97
Benign	0	0	5	0	5
Conflicting	—				9
Total	9	117	106	37	278

OTC

Primary Disease Associations & Inheritance

Population Genetics & Constraint

ClinVar Variant Classifications

Classification Summary

Curated Variants Distribution

Protein Context — Lollipop Plot

DECIPHER · Gene2Phenotype

Gene2Phenotype Curations

OMIM — Genotype-Phenotype Relationships

Gene Overview

ClinGen Curation

Disease Associations

External Resources

Variant Interpretation

Population Databases

Gene Resources