AADAT

Chr 4

aminoadipate aminotransferase

Also known as: KAT2, KATII, KYAT2

This gene encodes kynurenine aminotransferase II, a transaminase enzyme that catalyzes the transamination of kynurenine to kynurenic acid (which has neuroprotective properties) and participates in lysine catabolism through alpha-aminoadipic acid transamination. Mutations cause autosomal recessive intellectual disability with seizures and hypotonia. The gene shows moderate constraint against loss-of-function variants, indicating some intolerance to complete protein loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
8
Pubs (1 yr)
56
P/LP submissions
0%
P/LP missense
0.51
LOEUF
DN
Mechanism· predicted
Clinical SummaryAADAT
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 23 VUS of 98 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.146
Z-score 3.32
OE 0.26 (0.140.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.35Z-score
OE missense 0.56 (0.480.65)
126 obs / 225.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.26 (0.140.51)
00.351.4
Missense OE0.56 (0.480.65)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 6 / 23.3Missense obs/exp: 126 / 225.1Syn Z: 0.58
DN
0.7229th %ile
GOF
0.4381th %ile
LOF
0.3065th %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

98 submitted variants in ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic3
VUS23
Likely Benign3
53
Pathogenic
3
Likely Pathogenic
23
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
53
0
53
Likely Pathogenic
0
0
3
0
3
VUS
0
19
4
0
23
Likely Benign
0
2
1
0
3
Benign
0
0
0
0
0
Total02161082

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

View in ClinVar →

Protein Context — Lollipop Plot

AADAT · 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

No active trials found for this gene.

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Clinical Literature
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