AASS

Chr 7AR

aminoadipate-semialdehyde synthase

Also known as: LKR/SDH, LKRSDH, LORSDH

NCBI Gene: 10157ENSG00000008311UniProt: Q9UDR5

This gene encodes a bifunctional enzyme that catalyzes the first two steps in the mammalian lysine degradation pathway. The N-terminal and the C-terminal portions of this enzyme contain lysine-ketoglutarate reductase and saccharopine dehydrogenase activity, respectively, resulting in the conversion of lysine to alpha-aminoadipic semialdehyde. Mutations in this gene are associated with familial hyperlysinemia. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

HyperlysinemiaMIM #238700
AR
UniProtHyperlysinemia, 1
UniProt2,4-dienoyl-CoA reductase deficiency
316
ClinVar variants
48
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— AASS
🧬
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.
📋
ClinVar Variants
48 Pathogenic / Likely Pathogenic· 159 VUS of 316 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.81LOEUF
pLI 0.000
Z-score 2.58
OE 0.58 (0.43–0.81)
Tolerant

Typical tolerance to LoF variation

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.
0.88Z-score
OE missense 0.89 (0.82–0.96)
449 obs / 504.8 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.0.58 (0.43–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.82–0.96)
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.0.96
0≤1.21.6
LoF obs/exp: 26 / 44.6Missense obs/exp: 449 / 504.8Syn Z: 0.41

ClinVar Variant Classifications

316 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic13
VUS159
Likely Benign73
Benign33
Conflicting3
35
Pathogenic
13
Likely Pathogenic
159
VUS
73
Likely Benign
33
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
2
30
0
35
Likely Pathogenic
5
3
5
0
13
VUS
0
149
8
2
159
Likely Benign
0
6
31
36
73
Benign
0
4
27
2
33
Conflicting
—3
Total816410140316

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

View 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.

Gene2Phenotype Curations

AASS-related hyperlysinemia

strong
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hyperlysinemia

MIM #238700

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Sudden Cardiac Death in Anabolic-Androgenic Steroid Users: A Literature Review.
Torrisi M et al.·Medicina (Kaunas)
2020Review
Diagnostic Accuracy of the Aortic Dissection Detection Risk Score Plus D-Dimer for Acute Aortic Syndromes: The ADvISED Prospective Multicenter Study.
Nazerian P et al.·Circulation
2018
Therapeutic AASS inhibition by AAV-miRNA rescues glutaric aciduria type I severe phenotype in mice.
Segur-Bailach E et al.·Mol Ther
2025
Acute aortic syndromes: An internist's guide to the galaxy.
Morello F et al.·Eur J Intern Med
2022Review
Genetic basis of hyperlysinemia.
Houten SM et al.·Orphanet J Rare Dis
2013
Anabolic androgenic steroid-induced liver injury: An update.
Petrovic A et al.·World J Gastroenterol
2022Review
Anabolic Androgenic Steroids in Orthopaedic Surgery: Current Concepts and Clinical Applications.
Weber AE et al.·J Am Acad Orthop Surg Glob Res Rev
2022
MECHANISMS IN ENDOCRINOLOGY: Medical consequences of doping with anabolic androgenic steroids: effects on reproductive functions.
Nieschlag E et al.·Eur J Endocrinol
2015Review
Lysine metabolism is a novel metabolic tumor suppressor pathway in breast cancer.
Wu J et al.·Oncogene
2023
Evaluation of structural features of anabolic-androgenic steroids: entanglement for organ-specific toxicity.
Sinha A et al.·Steroids
2024Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools