AASS

Chr 7AR

aminoadipate-semialdehyde synthase

Also known as: LKR/SDH, LKRSDH, LORSDH

This gene encodes a bifunctional enzyme that catalyzes the first two steps in lysine degradation, converting lysine to alpha-aminoadipic semialdehyde through its lysine-ketoglutarate reductase and saccharopine dehydrogenase activities. Mutations cause hyperlysinemia, an autosomal recessive disorder of amino acid metabolism. The gene shows tolerance to loss-of-function variation (pLI near zero), consistent with the recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.811 OMIM phenotype
Clinical SummaryAASS
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Gene-Disease Validity (ClinGen)
hyperlysinemia · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 2.58
OE 0.58 (0.430.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.88Z-score
OE missense 0.89 (0.820.96)
449 obs / 504.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.58 (0.430.81)
00.351.4
Missense OE0.89 (0.820.96)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 26 / 44.6Missense obs/exp: 449 / 504.8Syn Z: 0.41
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongAASS-related hyperlysinemiaLOFAR

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

DN
0.6454th %ile
GOF
0.4776th %ile
LOF
0.3259th %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

AASS · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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