ASS1

argininosuccinate synthase 1

Basic information

Region (hg38): 9:130444960-130501274

Previous symbols: [ "ASS" ]

Links

ENSG00000130707 ∙ NCBI:445 ∙ OMIM:603470 ∙ HGNC:758 ∙ Uniprot:P00966 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• citrullinemia type I (Definitive), mode of inheritance: AR
• citrullinemia type I (Definitive), mode of inheritance: AR
• citrullinemia type I (Strong), mode of inheritance: AR
• acute neonatal citrullinemia type I (Supportive), mode of inheritance: AR
• adult-onset citrullinemia type I (Supportive), mode of inheritance: AR
• citrullinemia type I (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Citrullinemia	AR	Biochemical; Pharmacogenomic	To prevent decompensation, medical therapy (eg, with sodium phenylbutyrate, L-carnitine) and dietary management (including avoidance of excess protein) can be beneficial, especially in high-risk states such as during infectious episodes; In the acute state, control of hyperammonemia (eg, with sodium benzoate/phenylacetate or emergent hemodialysis, with dietary measures to prevent catabolism) with steps to prevent increased intracranial pressure can be beneficial; Avoidance of certain agents (eg, valproate) is warranted due to potential adverse events	Biochemical; Gastrointestinal; Neurologic	934749; 6807193; 3459354; 2358466; 3148074; 2246861; 7977368; 7557970; 11571557; 11804205; 11941481; 15334737; 15266621; 19006241; 20142522; 20301631; 22494546; 22594780; 22768672; 23099195; 23246278; 23430935; 23611581; 25135652

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ASS1 gene.

• Citrullinemia (510 variants)
• Citrullinemia type I (256 variants)
• not provided (116 variants)
• not specified (60 variants)
• Inborn genetic diseases (17 variants)
• Citrullinemia, mild (2 variants)
• ASS1-related condition (2 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASS1 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	147	3	151
missense	13	30	111	4		158
nonsense	16	17				33
start loss		2				2
frameshift	16	28	1			45
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)	6	29				35
splice region		2	7	46	3	58
non coding		2	11	73	36	122
Total	51	109	127	224	39

Highest pathogenic variant AF is 0.0000788

Variants in ASS1

This is a list of pathogenic ClinVar variants found in the ASS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-130444991-G-A		not specified	Likely benign (Sep 08, 2017)
9-130445039-G-C			Likely benign (Jun 17, 2021)
9-130445062-A-C			Benign (Jun 29, 2018)
9-130450309-C-T		not specified	Likely benign (Feb 06, 2018)
9-130450320-G-A			Likely benign (Aug 01, 2018)
9-130450341-C-T		not specified • Citrullinemia type I	Benign (Dec 10, 2015)
9-130451924-G-A			Likely benign (Oct 17, 2018)
9-130452009-G-A			Likely benign (Mar 10, 2019)
9-130452052-T-C		Citrullinemia type I	Benign (Jul 14, 2021)
9-130452131-C-T			Likely benign (Jun 09, 2020)
9-130452183-C-T			Likely benign (Sep 16, 2020)
9-130452212-G-A		Citrullinemia type I	Uncertain significance (Jan 13, 2018)
9-130452214-C-G		Citrullinemia type I • not specified • Citrullinemia	Uncertain significance (May 19, 2022)
9-130452225-C-T		Citrullinemia type I • Citrullinemia • not specified	Conflicting classifications of pathogenicity (Sep 08, 2023)
9-130452229-A-G		Citrullinemia type I	Likely pathogenic (Jan 10, 2017)
9-130452231-G-A		Citrullinemia type I	Likely pathogenic (Jun 13, 2016)
9-130452236-G-A		Citrullinemia	Uncertain significance (Aug 24, 2021)
9-130452242-G-C		Citrullinemia type I • Inborn genetic diseases • Citrullinemia	Uncertain significance (Aug 16, 2022)
9-130452244-T-G		Citrullinemia	Uncertain significance (May 04, 2022)
9-130452246-C-G		Citrullinemia	Likely benign (Mar 02, 2022)
9-130452246-C-T		Citrullinemia	Likely benign (Jan 27, 2024)
9-130452247-G-A		Citrullinemia type I • not specified • Citrullinemia	Conflicting classifications of pathogenicity (Oct 19, 2023)
9-130452256-G-C		Citrullinemia	Uncertain significance (Sep 01, 2021)
9-130452261-C-T		Citrullinemia	Likely benign (Jan 25, 2024)
9-130452267-C-T		Citrullinemia type I • Citrullinemia	Conflicting classifications of pathogenicity (Jan 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASS1	protein_coding	protein_coding	ENST00000372394	14	56346

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.51e-9	0.822	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.758	211	244	0.864	0.0000165	2700
Missense in Polyphen		48	74.302	0.64601		957
Synonymous	-1.11	112	98.1	1.14	0.00000716	764
Loss of Function	1.62	18	27.1	0.663	0.00000146	299

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000482	0.000481
Ashkenazi Jewish	0.00	0.00
East Asian	0.000328	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000176	0.000176
Middle Eastern	0.000328	0.000326
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: One of the enzymes of the urea cycle, the metabolic pathway transforming neurotoxic amonia produced by protein catabolism into inocuous urea in the liver of ureotelic animals. Catalyzes the formation of arginosuccinate from aspartate, citrulline and ATP and together with ASL it is responsible for the biosynthesis of arginine in most body tissues. {ECO:0000305|PubMed:18473344, ECO:0000305|PubMed:27287393, ECO:0000305|PubMed:8792870}.
• Disease: DISEASE: Citrullinemia 1 (CTLN1) [MIM:215700]: The classic form of citrullinemia, an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. It is a disorder of the urea cycle, usually manifesting in the first few days of life. Affected infants appear normal at birth, but as ammonia builds up in the body they present symptoms such as lethargy, poor feeding, vomiting, seizures and loss of consciousness. Less commonly, a milder form can develop later in childhood or adulthood. {ECO:0000269|PubMed:11708871, ECO:0000269|PubMed:11941481, ECO:0000269|PubMed:12815590, ECO:0000269|PubMed:14680976, ECO:0000269|PubMed:15863597, ECO:0000269|PubMed:16475226, ECO:0000269|PubMed:18473344, ECO:0000269|PubMed:19006241, ECO:0000269|PubMed:1943692, ECO:0000269|PubMed:2358466, ECO:0000269|PubMed:23611581, ECO:0000269|PubMed:24889030, ECO:0000269|PubMed:25179242, ECO:0000269|PubMed:27287393, ECO:0000269|PubMed:28111830, ECO:0000269|PubMed:7977368}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Arginine biosynthesis - Homo sapiens (human);Argininemia;Hyperornithinemia with gyrate atrophy (HOGA);Creatine deficiency, guanidinoacetate methyltransferase deficiency;L-arginine:glycine amidinotransferase deficiency;Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome];Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency);Citrullinemia Type I;Carbamoyl Phosphate Synthetase Deficiency;Argininosuccinic Aciduria;Hypoacetylaspartia;Urea Cycle;Aspartate Metabolism;Prolinemia Type II;Prolidase Deficiency (PD);Ornithine Transcarbamylase Deficiency (OTC Deficiency);Arginine and Proline Metabolism;Hyperprolinemia Type I;Hyperprolinemia Type II;Ornithine Aminotransferase Deficiency (OAT Deficiency);Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency);Canavan Disease;Alanine and aspartate metabolism;Amino Acid metabolism;Urea cycle and metabolism of amino groups;Alanine Aspartate Asparagine metabolism;Metabolism of polyamines;Metabolism of amino acids and derivatives;Metabolism;citrulline-nitric oxide cycle;urea cycle;Arginine Proline metabolism;Urea cycle (Consensus)

Recessive Scores

• pRec: 0.808

Intolerance Scores

• loftool: 0.0989
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.65

Haploinsufficiency Scores

• pHI: 0.487
• hipred: N
• hipred_score: 0.488
• ghis: 0.489

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.971

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ass1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: urea cycle;citrulline metabolic process;argininosuccinate metabolic process;kidney development;liver development;arginine biosynthetic process;aspartate metabolic process;acute-phase response;midgut development;aging;response to nutrient;circadian rhythm;response to zinc ion;response to mycotoxin;response to estradiol;positive regulation of nitric oxide biosynthetic process;response to growth hormone;diaphragm development;cellular response to lipopolysaccharide;cellular response to amino acid stimulus;cellular response to ammonium ion;cellular response to cAMP;cellular response to interferon-gamma;cellular response to tumor necrosis factor;cellular response to glucagon stimulus;cellular response to oleic acid;cellular response to amine stimulus;cellular response to laminar fluid shear stress;cellular response to dexamethasone stimulus;negative regulation of leukocyte cell-cell adhesion
• Cellular component: nucleus;cytoplasm;mitochondrial outer membrane;lysosome;endoplasmic reticulum;cytosol;perikaryon;myelin sheath;extracellular exosome;cell body fiber
• Molecular function: RNA binding;argininosuccinate synthase activity;protein binding;ATP binding;toxic substance binding;amino acid binding;identical protein binding