ADSS1

adenylosuccinate synthase 1

Basic information

Region (hg38): 14:104724174-104747325

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 (366 variants)
Inborn_genetic_diseases (117 variants)
Myopathy,_distal,_5 (32 variants)
ADSS1-related_disorder (20 variants)
not_specified (5 variants)
Fetal_akinesia_deformation_sequence_1 (1 variants)
Arthrogryposis_multiplex_congenita (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. These statistics are base on transcript: NM_000152328.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	80 clinvar	3 clinvar	84
missense	1 clinvar	2 clinvar	175 clinvar	2 clinvar	3 clinvar	183
nonsense	4 clinvar	1 clinvar				5
start loss						0
frameshift	7 clinvar	3 clinvar	2 clinvar			12
splice donor/acceptor (+/-2bp)		8 clinvar	3 clinvar	1 clinvar		12
Total	12	14	181	83	6

Highest pathogenic variant AF is 0.000180386

Loading clinvar variants...

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
Phenotype

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