LYL1

Summary

LYL1 (LYL1 basic helix-loop-helix family member, HGNC:6734) is a protein-coding gene on chromosome 19p13.13, encoding Protein lyl-1 (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.

Source: NCBI Gene 4066 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 63 total
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_005583

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6734
Approved symbol	LYL1
Name	LYL1 basic helix-loop-helix family member
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	bHLHa18
Ensembl gene	ENSG00000104903
Ensembl biotype	protein_coding
OMIM	151440
Entrez	4066

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000264824, ENST00000590120, ENST00000590974, ENST00000892171, ENST00000892172, ENST00000892173

RefSeq mRNA: 1 — MANE Select: NM_005583 NM_005583

CCDS: CCDS12292

Canonical transcript exons

ENST00000264824 — 4 exons

Exon	Start	End
ENSE00000682935	13100657	13100748
ENSE00000836401	13099033	13099734
ENSE00000836402	13100837	13101195
ENSE00001055150	13102531	13102858

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 95.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8740 / max 491.7862, expressed in 946 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179456	4.7354	378
179459	3.8364	593
179457	1.6621	169
179461	1.0787	362
179453	0.7401	244
179462	0.6767	244
179454	0.5327	129
179455	0.2441	100
179458	0.2101	61
179460	0.1233	67

Top tissues by expression

266 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	95.76	gold quality
granulocyte	CL:0000094	95.01	gold quality
monocyte	CL:0000576	94.82	gold quality
mononuclear cell	CL:0000842	94.47	gold quality
leukocyte	CL:0000738	94.27	gold quality
trabecular bone tissue	UBERON:0002483	92.71	gold quality
bone marrow	UBERON:0002371	90.67	gold quality
spleen	UBERON:0002106	89.72	gold quality
adult organism	UBERON:0007023	88.48	gold quality
bone marrow cell	CL:0002092	86.77	gold quality
vena cava	UBERON:0004087	86.52	silver quality
superficial temporal artery	UBERON:0001614	86.51	silver quality
triceps brachii	UBERON:0001509	85.04	gold quality
gluteal muscle	UBERON:0002000	84.82	gold quality
lymph node	UBERON:0000029	83.58	gold quality
olfactory bulb	UBERON:0002264	83.51	gold quality
type B pancreatic cell	CL:0000169	83.46	gold quality
apex of heart	UBERON:0002098	83.16	gold quality
male germ cell	CL:0000015	82.67	gold quality
left testis	UBERON:0004533	82.60	gold quality
sperm	CL:0000019	82.19	gold quality
right testis	UBERON:0004534	82.07	gold quality
vermiform appendix	UBERON:0001154	81.74	gold quality
caecum	UBERON:0001153	81.72	gold quality
testis	UBERON:0000473	80.08	gold quality
upper lobe of lung	UBERON:0008948	80.04	gold quality
upper lobe of left lung	UBERON:0008952	80.02	gold quality
right coronary artery	UBERON:0001625	79.83	gold quality
substantia nigra pars reticulata	UBERON:0001966	79.56	gold quality
placenta	UBERON:0001987	79.55	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	192.85
E-MTAB-7407	yes	176.77
E-GEOD-130473	yes	117.45
E-MTAB-9221	yes	18.85
E-HCAD-1	yes	13.35
E-MTAB-9388	yes	12.33
E-ANND-3	yes	7.59
E-HCAD-9	yes	7.54
E-CURD-112	yes	7.08
E-MTAB-9467	no	1.26

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets.

Target	Regulation
ANGPT2	Unknown
BRCA1	Activation
CCND3
CD4	Repression
CREB1	Unknown
ERG	Activation
ID1	Activation
MEF2C	Activation
NFKB1	Repression
NKX3-1	Activation
STMN1	Unknown
TAL1
TRMT1

Upstream regulators (CollecTRI, top): CREB1, GATA2, GATA3, HOXA10, HOXA1, LMO2, NKX2-5

miRNA regulators (miRDB)

9 targeting LYL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-4769-3P	97.95	68.17	1002
HSA-MIR-6817-5P	97.95	67.86	1026

Literature-anchored findings (GeneRIF, showing 13)

• LYL1 may play a role in early hematopoiesis and may be a potential oncogenic factor in AML (PMID:16094422)
• Lyl1 interacts with CREB1 and alters expression of CREB1 target genes. (PMID:18160048)
• Over-expression of LYL1 is highly associated with AML as well as ALL. (PMID:19176012)
• Multiple mechanisms which activate LYL1 in leukemic cells, including structural genomic alterations, namely microdeletion or amplification, together with the involvement of prominent oncogenic transcription factors. (PMID:19608273)
• The abnormal expression and protein interaction of LMO2 and LYL1 may play a role in the abnormal proliferation and differentiation of myeloid hematopoietic cells. (PMID:19671288)
• LYL1 activity is required for the maturation of newly formed blood vessels in adulthood. (PMID:20418284)
• LYL1 degradation is directed by a N-terminal PEST rich site in a phosphorylation-independent manner. (PMID:20844761)
• Transcriptional regulators cooperate to establish or maintain primitive stem cell-like signatures in leukemic cells. (PMID:23327922)
• In t(8;21) leukemia cells, LYL1 functions as a component of the stable AML1-ETO-containing transcription factor complex (AETFC). The AETFC components cooperatively regulate gene expression and contribute to leukemogenesis. (PMID:23812588)
• Despite not being identified as an independent prognostic factor in UCEC, LYL1 gene amplification is associated with other poor prognostic factors and correlated with upregulation of cancer-related pathways. (PMID:29716549)
• Repression of LYL1 contributes to t(8;21) leukemic cell differentiation. (PMID:30755707)
• Super-enhancer profiling identifies novel critical and targetable cancer survival gene LYL1 in pediatric acute myeloid leukemia. (PMID:35842703)
• LYL1 facilitates AETFC assembly and gene activation by recruiting CARM1 in t(8;21) AML. (PMID:36215477)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lyl1	ENSMUSG00000034041
rattus_norvegicus	Lyl1	ENSRNOG00000002950

Paralogs (4): TAL1 (ENSG00000162367), NHLH1 (ENSG00000171786), NHLH2 (ENSG00000177551), TAL2 (ENSG00000186051)

Protein

Protein identifiers

Protein lyl-1 — P12980 (reviewed: P12980)

Alternative names: Class A basic helix-loop-helix protein 18, Lymphoblastic leukemia-derived sequence 1

All UniProt accessions (2): P12980, K7ER61

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein.

Subcellular location. Nucleus.

Disease relevance. A chromosomal aberration involving LYL1 may be a cause of a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(7;19)(q35;p13) with TCRB.

RefSeq proteins (1): NP_005574* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR040238	TAL-like	Family

Pfam: PF00010

UniProt features (10 total): compositionally biased region 3, region of interest 2, modified residue 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12980-F1	66.64	0.26

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 260, 276

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-9031628	NGF-stimulated transcription
R-HSA-162582	Signal Transduction
R-HSA-166520	Signaling by NTRKs
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-198725	Nuclear Events (kinase and transcription factor activation)
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 268 (showing top): MODULE_255, GOBP_B_CELL_ACTIVATION, GCANCTGNY_MYOD_Q6, AREB6_03, MODULE_317, SP1_Q2_01, GOLDRATH_ANTIGEN_RESPONSE, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GATA3_01, GATA6_01, GATA1_04, BYSTROEM_CORRELATED_WITH_IL5_UP, GATA1_03, SANSOM_APC_TARGETS_DN, NEMETH_INFLAMMATORY_RESPONSE_LPS_DN

GO Biological Process (7): blood vessel maturation (GO:0001955), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), B cell differentiation (GO:0030183), positive regulation of DNA-templated transcription (GO:0045893), definitive hemopoiesis (GO:0060216), SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition (GO:0006617)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), protein dimerization activity (GO:0046983), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleoplasm (GO:0005654), nucleus (GO:0005634), signal recognition particle, endoplasmic reticulum targeting (GO:0005786)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Nuclear Events (kinase and transcription factor activation)	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by NTRKs	1
Signaling by NTRK1 (TRKA)	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
blood vessel development	1
anatomical structure maturation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
lymphocyte differentiation	1
B cell activation	1
positive regulation of RNA biosynthetic process	1
hemopoiesis	1
SRP-dependent cotranslational protein targeting to membrane	1
protein-containing complex assembly	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
protein binding	1
binding	1
chromosome	1
nuclear lumen	1
intracellular membrane-bounded organelle	1
signal recognition particle	1

Protein interactions and networks

STRING

898 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYL1	LMO2	P25791	997
LYL1	LDB1	Q86U70	967
LYL1	LDB2	O43679	965
LYL1	TCF3	P15883	948
LYL1	CBFB	Q13951	922
LYL1	RUNX1	Q01196	897
LYL1	GATA2	P23769	887
LYL1	LMO1	P25800	857
LYL1	TLX3	O43711	851
LYL1	TLX1	P31314	829
LYL1	CBFA2T3	O75081	775
LYL1	GFI1B	Q5VTD9	757
LYL1	BCL11B	Q9C0K0	727
LYL1	GATA1	P15976	721
LYL1	TAL1	P17542	692

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TAL1	KDM1A	psi-mi:“MI:0914”(association)	0.560
TRIM33	CBFA2T2	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): LYL1 (Reconstituted Complex), LYL1 (Affinity Capture-MS), LYL1 (Two-hybrid), LYL1 (Affinity Capture-RNA), NFKB1 (Reconstituted Complex), NFKBIA (Reconstituted Complex), NFKB1 (Affinity Capture-Western), LMO1 (Two-hybrid), LMO2 (Two-hybrid), TCF3 (Two-hybrid), TCF3 (Reconstituted Complex), TCF3 (Affinity Capture-Western), LYL1 (Affinity Capture-MS), LYL1 (Affinity Capture-MS), LYL1 (Two-hybrid)

ESM2 similar proteins: A0A286YF58, A0A494C0N9, A0A494C0Y3, A0A7I2V3R4, A2VDX9, A6NIN4, D3YXK1, G3UXB3, O15370, O15522, O35392, O70218, O70220, O89113, P0DPE3, P12980, P17542, P22091, P28283, P82976, Q04890, Q05916, Q05917, Q13461, Q14V87, Q15270, Q19A40, Q5T230, Q5VY09, Q63244, Q6F5E0, Q6SPE9, Q6SPF0, Q7RTU7, Q80WY3, Q8TD94, Q8WY41, Q8WZ71, Q91XV7, Q96Q04

Diamond homologs: A8E5T6, B6VQA1, D2CLZ9, O09105, O13125, O13126, O35437, O35885, O42202, O42606, O43680, O57598, O60682, O73823, O88940, O93507, O96642, P12980, P13903, P17542, P19360, P22091, P24899, P26687, P46581, P48985, P48986, P48987, P57101, P57102, P59101, P61295, P61296, P70447, P70595, P70660, P70661, P79765, P79766, P79782

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
LYL1	“up-regulates quantity by expression”	ANGPT2	“transcriptional regulation”
NKX2-5	“up-regulates quantity by expression”	LYL1	“transcriptional regulation”
LYL1	“up-regulates quantity by expression”	ERG	“transcriptional regulation”
LYL1	“up-regulates quantity by expression”	MEF2C	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

63 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

916 predictions. Top by Δscore:

Variant	Effect	Δscore
19:13099730:GTGCC:G	acceptor_gain	1.0000
19:13099731:TGCC:T	acceptor_gain	1.0000
19:13099732:GCC:G	acceptor_gain	1.0000
19:13099733:CC:C	acceptor_gain	1.0000
19:13099733:CCC:C	acceptor_gain	1.0000
19:13099734:CC:C	acceptor_gain	1.0000
19:13099735:C:CC	acceptor_gain	1.0000
19:13099736:T:A	acceptor_loss	1.0000
19:13100747:CA:C	acceptor_gain	1.0000
19:13100749:C:CC	acceptor_gain	1.0000
19:13099735:C:T	acceptor_gain	0.9900
19:13099737:G:C	acceptor_gain	0.9900
19:13099737:G:GC	acceptor_gain	0.9900
19:13100745:GACA:G	acceptor_gain	0.9900
19:13101429:C:A	donor_gain	0.9900
19:13102526:CTTA:C	donor_loss	0.9900
19:13102527:TTAC:T	donor_loss	0.9900
19:13102528:TA:T	donor_loss	0.9900
19:13102529:ACC:A	donor_gain	0.9900
19:13102530:C:CT	donor_loss	0.9900
19:13102530:CCC:C	donor_gain	0.9900
19:13100749:CT:C	acceptor_loss	0.9800
19:13102529:AC:A	donor_gain	0.9800
19:13102530:CC:C	donor_gain	0.9800
19:13099731:TGCCC:T	acceptor_gain	0.9700
19:13099732:GCCC:G	acceptor_gain	0.9700
19:13099733:CCCT:C	acceptor_gain	0.9700
19:13099734:CCT:C	acceptor_gain	0.9700
19:13099735:CTGT:C	acceptor_gain	0.9700
19:13099736:T:G	acceptor_gain	0.9700

AlphaMissense

1772 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:13099598:C:A	K188N	1.000
19:13099598:C:G	K188N	1.000
19:13099599:T:A	K188M	1.000
19:13099600:T:C	K188E	1.000
19:13099600:T:G	K188Q	1.000
19:13099644:A:G	L173P	1.000
19:13099652:G:C	F170L	1.000
19:13099652:G:T	F170L	1.000
19:13099653:A:C	F170C	1.000
19:13099653:A:G	F170S	1.000
19:13099654:A:G	F170L	1.000
19:13099570:A:G	Y198H	0.999
19:13099578:G:T	A195D	0.999
19:13099581:A:G	L194P	0.999
19:13099587:A:G	L192P	0.999
19:13099587:A:T	L192H	0.999
19:13099599:T:G	K188T	0.999
19:13099602:C:A	S187I	0.999
19:13099635:A:G	L176P	0.999
19:13099641:C:A	R174M	0.999
19:13099644:A:T	L173Q	0.999
19:13099661:G:C	N167K	0.999
19:13099661:G:T	N167K	0.999
19:13099665:A:T	V166D	0.999
19:13099673:C:A	Q163H	0.999
19:13099673:C:G	Q163H	0.999
19:13099684:G:T	R160S	0.999
19:13099685:C:A	E159D	0.999
19:13099685:C:G	E159D	0.999
19:13099686:T:A	E159V	0.999

dbSNP variants (sampled 300 via entrez): RS1000184280 (19:13103088 C>A,T), RS1000344999 (19:13100443 G>T), RS1000568060 (19:13103855 C>T), RS1000947147 (19:13099142 C>A,T), RS1001178320 (19:13099792 T>A), RS1001251894 (19:13099484 C>G,T), RS1002036215 (19:13098567 T>G), RS1002098569 (19:13104363 A>C), RS1002258304 (19:13104228 G>A,C,T), RS1002488845 (19:13103717 C>T), RS1003081531 (19:13102715 C>A,T), RS1003118579 (19:13101362 C>G), RS1003391 (19:13101310 A>G,T), RS1003392 (19:13101314 A>G), RS1003393 (19:13101400 C>T)

Disease associations

OMIM: gene MIM:151440 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST005141_30	Cognitive ability (MTAG)	3.000000e-09
GCST009523_66	Household income	4.000000e-10
GCST009524_319	Household income (MTAG)	2.000000e-14
GCST010002_148	Refractive error	2.000000e-11
GCST010703_320	Brain morphology (MOSTest)	2.000000e-21
GCST90002393_645	Monocyte count	6.000000e-16
GCST90002394_443	Monocyte percentage of white cells	7.000000e-13
GCST90002396_22	Mean reticulocyte volume	7.000000e-15
GCST90002400_269	Plateletcrit	5.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009695	household income
EFO:0004346	neuroimaging measurement
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression, increases expression	2
Cadmium Chloride	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
thallium sulfate	increases expression	1
beta-lapachone	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, decreases expression, affects response to substance	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cytarabine	decreases response to substance	1
Estradiol	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Plant Extracts	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.