YES1

Chr 18

YES proto-oncogene 1, Src family tyrosine kinase

Also known as: HsT441, P61-YES, Yes, c-yes

NCBI Gene: 7525ENSG00000176105UniProt: P07947

The YES1 protein is a non-receptor tyrosine kinase of the Src family that regulates cell growth, survival, cell-cell adhesion, and cytoskeleton remodeling through phosphorylation of downstream substrates following activation by receptor tyrosine kinases. This gene is highly constrained against loss-of-function variants (LOEUF 0.65), but no human disease phenotypes have been definitively associated with YES1 mutations to date. The inheritance pattern for potential YES1-related disorders would be autosomal.

Summary from RefSeq, UniProt
Research Assistant →
4
Active trials
36
Pubs (1 yr)
130
P/LP submissions
0%
P/LP missense
0.65
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— YES1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
125 unique Pathogenic / Likely Pathogenic· 93 VUS of 240 total submissions
💊
Clinical Trials
4 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
0.65LOEUF
pLI 0.000
Z-score 3.09
OE 0.41 (0.27–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.16Z-score
OE missense 0.81 (0.72–0.90)
232 obs / 287.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.27–0.65)
0≤0.351.4
Missense OE0.81 (0.72–0.90)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 13 / 31.8Missense obs/exp: 232 / 287.4Syn Z: -0.09
DN
0.75top 25%
GOF
0.78top 25%
LOF
0.2774th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

240 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic122
Likely Pathogenic3
VUS93
Likely Benign8
122
Pathogenic
3
Likely Pathogenic
93
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
122
0
122
Likely Pathogenic
0
0
3
0
3
VUS
0
56
37
0
93
Likely Benign
0
2
6
0
8
Benign
0
0
0
0
0
Total0581680226

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

View in ClinVar →

Protein Context — Lollipop Plot

YES1 · protein map & ClinVar variants

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

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