ADSS1

adenylosuccinate synthase 1

Basic information

Region (hg38): 14:104724228-104747325

Previous symbols: [ "ADSSL1" ]

Links

ENSG00000185100 ∙ NCBI:122622 ∙ OMIM:612498 ∙ HGNC:20093 ∙ Uniprot:Q8N142 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myopathy, distal, 5 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopathy, distal, 5	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	Musculoskeletal	26506222; 28268051; 32331917; 32646962

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADSS1 gene.

• not provided (14 variants)
• Myopathy, distal, 5 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADSS1 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	83	8	92
missense		1	177		4	182
nonsense	5					5
start loss			6		1	7
frameshift	9	2	2			13
inframe indel			2			2
splice donor/acceptor (+/-2bp)		6	3	1		10
splice region			6	16	2	24
non coding				53	9	62
Total	14	9	191	137	22

Highest pathogenic variant AF is 0.0000853

Variants in ADSS1

This is a list of pathogenic ClinVar variants found in the ADSS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-104724300-G-GC		Myopathy, distal, 5	Uncertain significance (Jan 01, 2019)
14-104724307-G-A		Inborn genetic diseases	Uncertain significance (Nov 03, 2023)
14-104724323-A-G		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
14-104724348-G-A			Likely benign (Nov 01, 2022)
14-104724362-C-A		Inborn genetic diseases	Uncertain significance (Apr 23, 2024)
14-104724367-G-C		Inborn genetic diseases	Uncertain significance (Jun 11, 2024)
14-104724371-C-T		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
14-104724373-G-A		Inborn genetic diseases	Uncertain significance (Nov 28, 2023)
14-104724373-G-C		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
14-104724399-C-G		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
14-104724434-C-T		Inborn genetic diseases	Uncertain significance (May 29, 2024)
14-104724445-A-G		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
14-104724461-AGGTGCGGGCTGGGGCGCCG-A		not specified	Uncertain significance (Apr 04, 2024)
14-104729867-GTCGTGGGGAGGAGCGTGGCGTCGGCA-G			Uncertain significance (Feb 21, 2022)
14-104729869-CGTGGGGAGGAGCGTGGCGTCGGCATG-C			Uncertain significance (Oct 17, 2022)
14-104729890-G-A		ADSS1-related disorder	Likely benign (Sep 03, 2020)
14-104729893-A-C		ADSS1-related disorder	Benign (Feb 01, 2024)
14-104729893-A-G			Uncertain significance (Jan 19, 2024)
14-104729893-ATG-GTC			Uncertain significance (Aug 08, 2022)
14-104729895-G-C			Uncertain significance (Jan 19, 2024)
14-104729895-G-T			Uncertain significance (Dec 02, 2022)
14-104729897-T-G			Uncertain significance (Nov 05, 2021)
14-104729898-G-A		Myopathy, distal, 5	Benign (Feb 01, 2024)
14-104729905-A-G			Uncertain significance (Aug 05, 2022)
14-104729914-G-A			Uncertain significance (Apr 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADSS1	protein_coding	protein_coding	ENST00000332972	13	23140

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.82e-7	0.982	125578	2	168	125748	0.000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0328	306	304	1.01	0.0000184	3206
Missense in Polyphen		148	139.96	1.0574		1315
Synonymous	0.811	117	129	0.909	0.00000874	1007
Loss of Function	2.20	15	27.4	0.547	0.00000145	294

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00205	0.00205
Ashkenazi Jewish	0.000994	0.000993
East Asian	0.00131	0.00131
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000469	0.000457
Middle Eastern	0.00131	0.00131
South Asian	0.000557	0.000523
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the purine nucleotide cycle (PNC), which interconverts IMP and AMP to regulate the nucleotide levels in various tissues, and which contributes to glycolysis and ammoniagenesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP. {ECO:0000269|PubMed:26506222}.
• Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Hypoacetylaspartia;Aspartate Metabolism;Canavan Disease;adenosine ribonucleotides <i>de novo</i> biosynthesis;Metabolism of nucleotides;Alanine Aspartate Asparagine metabolism;Metabolism;Nucleobase biosynthesis;Purine nucleotides nucleosides metabolism;superpathway of purine nucleotide salvage;Purine ribonucleoside monophosphate biosynthesis;purine nucleotides <i>de novo</i> biosynthesis (Consensus)

Recessive Scores

• pRec: 0.155

Intolerance Scores

• loftool: 0.875
• rvis_EVS: -0.02
• rvis_percentile_EVS: 52.25

Haploinsufficiency Scores

• pHI: 0.257
• hipred: Y
• hipred_score: 0.542
• ghis: 0.610

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.683

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adssl1

Zebrafish Information Network

• Gene name: adssl1
• Affected structure: skeletal muscle cell
• Phenotype tag: abnormal
• Phenotype quality: apoptotic

Gene ontology

• Biological process: immune system process;AMP biosynthetic process;aspartate metabolic process;glutamine metabolic process;purine ribonucleoside monophosphate biosynthetic process;response to muscle activity;cellular response to drug;response to starvation;'de novo' AMP biosynthetic process;IMP metabolic process;cellular response to electrical stimulus
• Cellular component: cytoplasm;cytosol
• Molecular function: magnesium ion binding;GTPase activity;adenylosuccinate synthase activity;GTP binding;phosphate ion binding;protein homodimerization activity;actin filament binding