LYL1

Chr 19

LYL1 basic helix-loop-helix family member

Also known as: bHLHa18

NCBI Gene: 4066ENSG00000104903UniProt: P12980

This gene represents a basic helix-loop-helix transcription factor. The encoded protein may play roles in blood vessel maturation and hematopoeisis. A translocation between this locus and the T cell receptor beta locus (GeneID 6957) on chromosome 7 has been associated with acute lymphoblastic leukemia. [provided by RefSeq, Sep 2010]

94
ClinVar variants
23
Pathogenic / LP
0.77
pLI score
0
Active trials
Clinical Summary— LYL1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 66 VUS of 94 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.61LOEUF
pLI 0.773
Z-score 2.05
OE 0.00 (0.00–0.61)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.95Z-score
OE missense 0.75 (0.63–0.90)
85 obs / 113.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.61)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.63–0.90)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 0 / 4.9Missense obs/exp: 85 / 113.5Syn Z: -0.08

ClinVar Variant Classifications

94 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic3
VUS66
Likely Benign2
20
Pathogenic
3
Likely Pathogenic
66
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
3
0
3
VUS
0
57
9
0
66
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total05932091

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

View in ClinVar →

Protein Context — Lollipop Plot

LYL1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases.
Dai YT et al.·Proc Natl Acad Sci U S A
2022Cohort
Targeting LMO2-induced autocrine FLT3 signaling to overcome chemoresistance in early T-cell precursor acute lymphoblastic leukemia.
Tremblay CS et al.·Leukemia
2025
Lyl1 interacts with CREB1 and alters expression of CREB1 target genes.
San-Marina S et al.·Biochim Biophys Acta
2008
The paralogous hematopoietic regulators Lyl1 and Scl are coregulated by Ets and GATA factors, but Lyl1 cannot rescue the early Scl-/- phenotype.
Chan WY et al.·Blood
2007
Role of GATA2 in Human NK Cell Development.
Wang D et al.·Crit Rev Immunol
2021Review
LYL1 activity is required for the maturation of newly formed blood vessels in adulthood.
Pirot N et al.·Blood
2010
Molecular subgroups of T-cell acute lymphoblastic leukemia in adults treated according to pediatric-based GMALL protocols.
Neumann M et al.·Leukemia
2024
Gene expression profiling in T-cell acute lymphoblastic leukemia.
Ferrando AA et al.·Semin Hematol
2003Review
Oncogenic potential of the transcription factor LYL1 in acute myeloblastic leukemia.
Meng YS et al.·Leukemia
2005
Suspected leukemia oncoproteins CREB1 and LYL1 regulate Op18/STMN1 expression.
San-Marina S et al.·Biochim Biophys Acta
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Role of different Lyl1 transcripts in zebrafish primitive hematopoiesis.
Lin JH et al.·Yi Chuan
2025Functional
Functional circuits of LYL1 controlled by supraphysiological androgen in prostate cancer cells to regulate cell senescence.
Heidari Horestani M et al.·Cell Commun Signal
2024🔓 Open AccessFunctional
Multiple primary tumors in a patient with non‑small‑cell lung cancer harboring mutations in ERCC6 and LYL1: A case report.
Wu H et al.·Oncol Lett
2025🔓 Open AccessCase report
SPI1-KLF1/LYL1 axis regulates lineage commitment during endothelial-to-hematopoietic transition from human pluripotent stem cells.
Qu K et al.·iScience
2024🔓 Open Access
LYL1 facilitates AETFC assembly and gene activation by recruiting CARM1 in t(8;21) AML.
Chen Q et al.·Proc Natl Acad Sci U S A
2022🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools