AASS

aminoadipate-semialdehyde synthase

Basic information

Region (hg38): 7:122064583-122144308

Links

ENSG00000008311 ∙ NCBI:10157 ∙ OMIM:605113 ∙ HGNC:17366 ∙ Uniprot:Q9UDR5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperlysinemia (Strong), mode of inheritance: AR
• hyperlysinemia (Strong), mode of inheritance: AR
• hyperlysinemia (Moderate), mode of inheritance: AR
• hyperlysinemia (Supportive), mode of inheritance: AR
• hyperlysinemia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperlysinemia, type I	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical	14209691; 5796356; 5557172; 934735; 10775527; 23570448
Other than increased serum lysine, the evidence of a common phenotype is unclear, and there does not appear to be evidence that measures such as protein restriction or other metabolic treatments are effective

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AASS gene.

• Hyperlysinemia (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AASS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	23	2	26
missense		1	84	4	4	93
nonsense	2	1				3
start loss		1				1
frameshift	1	1				2
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			3	8	2	13
non coding			1	10	22	33
Total	3	6	86	37	28

Highest pathogenic variant AF is 0.0000263

Variants in AASS

This is a list of pathogenic ClinVar variants found in the AASS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-122076508-T-C		not specified • Hyperlysinemia;Saccharopinuria	Uncertain significance (Jul 21, 2022)
7-122076541-C-T		Inborn genetic diseases	Uncertain significance (Jan 13, 2021)
7-122076556-C-T			Benign (Jul 31, 2023)
7-122076559-T-C			Uncertain significance (Jun 11, 2023)
7-122076601-A-G			Uncertain significance (Feb 06, 2022)
7-122077833-CTTAC-AA		Hyperlysinemia	Pathogenic (Nov 01, 2013)
7-122077866-G-A			Likely benign (May 01, 2022)
7-122077867-G-T			Uncertain significance (Jun 26, 2023)
7-122077906-T-C		Inborn genetic diseases	Uncertain significance (Jul 18, 2022)
7-122077960-G-A			Uncertain significance (Jun 03, 2022)
7-122077963-T-C		Inborn genetic diseases	Uncertain significance (May 25, 2022)
7-122077984-C-T			Uncertain significance (Jul 05, 2022)
7-122077988-T-C		Inborn genetic diseases	Uncertain significance (Oct 17, 2023)
7-122078852-C-G			Likely benign (Nov 14, 2022)
7-122078879-A-T		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
7-122078888-T-C			Benign (Nov 16, 2023)
7-122078888-T-G		Inborn genetic diseases	Uncertain significance (Feb 10, 2022)
7-122078919-G-A			Likely pathogenic (Nov 12, 2023)
7-122078951-C-A		Hyperlysinemia	Likely pathogenic (Mar 29, 2024)
7-122078966-G-A			Likely benign (Jan 16, 2022)
7-122079532-C-T			Benign (May 08, 2021)
7-122079609-T-C			Uncertain significance (Mar 23, 2022)
7-122079620-A-T		not specified	Uncertain significance (Dec 17, 2015)
7-122079643-G-T		Inborn genetic diseases	Uncertain significance (Mar 30, 2022)
7-122079654-T-G		Hyperlysinemia	Uncertain significance (Jul 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AASS	protein_coding	protein_coding	ENST00000393376	23	68634

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.31e-12	0.991	125673	0	75	125748	0.000298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.882	449	505	0.889	0.0000267	6058
Missense in Polyphen		157	194.48	0.80729		2270
Synonymous	0.410	172	179	0.961	0.00000960	1785
Loss of Function	2.58	26	44.6	0.583	0.00000192	635

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000366	0.000366
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000544	0.000544
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000319	0.000316
Middle Eastern	0.000544	0.000544
South Asian	0.000589	0.000588
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Bifunctional enzyme that catalyzes the first two steps in lysine degradation. The N-terminal and the C-terminal contain lysine-ketoglutarate reductase and saccharopine dehydrogenase activity, respectively.
• Disease: DISEASE: Hyperlysinemia, 1 (HYPLYS1) [MIM:238700]: An autosomal recessive metabolic condition with variable clinical features. Some patients present with non-specific seizures, hypotonia, or mildly delayed psychomotor development, and increased serum lysine and pipecolic acid on laboratory analysis. However, about half of the probands are reported to be asymptomatic, and hyperlysinemia is generally considered to be a benign metabolic variant. {ECO:0000269|PubMed:10775527}. Note=The disease is caused by mutations affecting the gene represented in this entry. In hyperlysinemia 1, both enzymatic functions of AASS are defective and patients have increased serum lysine and possibly increased saccharopine. Some individuals, however, retain significant amounts of lysine-ketoglutarate reductase and present with saccharopinuria, a metabolic condition with few, if any, clinical manifestations. {ECO:0000305|PubMed:463877}.; DISEASE: 2,4-dienoyl-CoA reductase deficiency (DECRD) [MIM:616034]: A rare, autosomal recessive, inborn error of polyunsaturated fatty acids and lysine metabolism, resulting in mitochondrial dysfunction. Affected individuals have a severe encephalopathy with neurologic and metabolic abnormalities beginning in early infancy. Laboratory studies show increased C10:2 carnitine levels and hyperlysinemia. {ECO:0000269|PubMed:24847004}. Note=The protein represented in this entry is involved in disease pathogenesis. A selective decrease in mitochondrial NADP(H) levels due to NADK2 mutations causes a deficiency of NADPH-dependent mitochondrial enzymes, such as DECR1 and AASS. {ECO:0000269|PubMed:24847004}.
• Pathway: Lysine degradation - Homo sapiens (human);Lysine Degradation;Hyperlysinemia I, Familial;2-aminoadipic 2-oxoadipic aciduria;Pyridoxine dependency with seizures;Saccharopinuria/Hyperlysinemia II;Glutaric Aciduria Type I;Hyperlysinemia II or Saccharopinuria;Vitamin B6-dependent and responsive disorders;Lysine catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Metabolism;Lysine degradation;Lysine metabolism;lysine degradation I (saccharopine pathway) (Consensus)

Intolerance Scores

• loftool: 0.355
• rvis_EVS: -0.91
• rvis_percentile_EVS: 10.12

Haploinsufficiency Scores

• pHI: 0.547
• hipred: N
• hipred_score: 0.492
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Aass

Gene ontology

• Biological process: lysine catabolic process;lysine biosynthetic process via aminoadipic acid;L-lysine catabolic process to acetyl-CoA via saccharopine;protein tetramerization;oxidation-reduction process
• Cellular component: cytoplasm;mitochondrion;mitochondrial matrix;intracellular membrane-bounded organelle
• Molecular function: saccharopine dehydrogenase activity;saccharopine dehydrogenase (NADP+, L-lysine-forming) activity;saccharopine dehydrogenase (NAD+, L-glutamate-forming) activity