ADSS1

Chr 14AR

adenylosuccinate synthase 1

Also known as: ADSSL1, MPD5

NCBI Gene: 122622ENSG00000185100UniProt: Q8N142OMIM: 612498

This gene encodes adenylosuccinate synthetase, a muscle-specific enzyme that catalyzes the conversion of inosine monophosphate to adenosine monophosphate in the purine nucleotide cycle. Mutations cause autosomal recessive myopathy with distal muscle involvement and adolescent onset. The gene shows low constraint to loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.841 OMIM phenotype
Clinical Summary— ADSS1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 251 VUS of 500 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.000
Z-score 2.20
OE 0.55 (0.36–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.03Z-score
OE missense 1.01 (0.92–1.10)
306 obs / 304.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.55 (0.36–0.84)
0≤0.351.4
Missense OE1.01 (0.92–1.10)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 15 / 27.4Missense obs/exp: 306 / 304.4Syn Z: 0.81
DN
0.74top 25%
GOF
0.5465th %ile
LOF
0.3454th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic11
VUS251
Likely Benign189
Benign13
Conflicting3
29
Pathogenic
11
Likely Pathogenic
251
VUS
189
Likely Benign
13
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
18
0
29
Likely Pathogenic
11
0
0
0
11
VUS
8
229
12
2
251
Likely Benign
0
0
87
102
189
Benign
0
1
11
1
13
Conflicting
—3
Total30230128105496

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

View in ClinVar →

Protein Context — Lollipop Plot

ADSS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients