HEYL

Summary

HEYL (hes related family bHLH transcription factor with YRPW motif like, HGNC:4882) is a protein-coding gene on chromosome 1p34.2, encoding Hairy/enhancer-of-split related with YRPW motif-like protein (Q9NQ87). Downstream effector of Notch signaling which may be required for cardiovascular development.

This gene encodes a member of the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcription factors. The sequence of the encoded protein contains a conserved bHLH and orange domain, but its YRPW motif has diverged from other HESR family members. It is thought to be an effector of Notch signaling and a regulator of cell fate decisions. Alternatively spliced transcript variants have been found, but their biological validity has not been determined.

Source: NCBI Gene 26508 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_014571

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4882
Approved symbol	HEYL
Name	hes related family bHLH transcription factor with YRPW motif like
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	bHLHb33, HEY3, HESR3
Ensembl gene	ENSG00000163909
Ensembl biotype	protein_coding
OMIM	609034
Entrez	26508

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000372852, ENST00000851853

RefSeq mRNA: 1 — MANE Select: NM_014571 NM_014571

CCDS: CCDS439

Canonical transcript exons

ENST00000372852 — 5 exons

Exon	Start	End
ENSE00001079557	39623435	39627180
ENSE00001127617	39630227	39630308
ENSE00001127625	39631496	39631579
ENSE00001458815	39639546	39639643
ENSE00003502744	39632649	39632715

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 96.26.

FANTOM5 (CAGE): breadth broad, TPM avg 5.0201 / max 323.3804, expressed in 649 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11869	4.3516	526
11871	0.3112	154
11870	0.1792	87
201479	0.1781	91

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	96.26	gold quality
left coronary artery	UBERON:0001626	95.23	gold quality
coronary artery	UBERON:0001621	95.09	gold quality
body of pancreas	UBERON:0001150	94.43	gold quality
tibial artery	UBERON:0007610	93.47	gold quality
popliteal artery	UBERON:0002250	93.45	gold quality
ascending aorta	UBERON:0001496	93.35	gold quality
aorta	UBERON:0000947	93.25	gold quality
thoracic aorta	UBERON:0001515	93.25	gold quality
apex of heart	UBERON:0002098	93.23	gold quality
right atrium auricular region	UBERON:0006631	92.99	gold quality
descending thoracic aorta	UBERON:0002345	92.25	gold quality
right lung	UBERON:0002167	91.29	gold quality
cardiac atrium	UBERON:0002081	90.51	gold quality
pancreas	UBERON:0001264	89.98	gold quality
heart left ventricle	UBERON:0002084	89.52	gold quality
heart	UBERON:0000948	89.41	gold quality
cardiac ventricle	UBERON:0002082	89.28	gold quality
left uterine tube	UBERON:0001303	88.65	gold quality
upper lobe of left lung	UBERON:0008952	86.69	gold quality
upper lobe of lung	UBERON:0008948	86.28	gold quality
right lobe of thyroid gland	UBERON:0001119	86.00	gold quality
body of uterus	UBERON:0009853	85.58	gold quality
islet of Langerhans	UBERON:0000006	85.21	gold quality
buccal mucosa cell	CL:0002336	85.02	silver quality
heart right ventricle	UBERON:0002080	84.98	gold quality
left lobe of thyroid gland	UBERON:0001120	84.56	gold quality
endocervix	UBERON:0000458	83.84	gold quality
thyroid gland	UBERON:0002046	83.01	gold quality
adenohypophysis	UBERON:0002196	82.99	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	11.11
E-ANND-3	yes	7.48
E-ENAD-27	yes	6.40
E-GEOD-109979	no	44.30

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
AR	Repression
HES1	Repression
HEY1	Repression
HEY2	Repression
NEUROG2	Activation
NOTCH1
SMTN	Repression

Upstream regulators (CollecTRI, top): JAG1, NOTCH1, NOTCH3, ROBO1

miRNA regulators (miRDB)

162 targeting HEYL, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442

Literature-anchored findings (GeneRIF, showing 10)

• In this study, we analyzed the effects of HESR1, -2, and -3 on DAT1 expression in human neuroblastoma SH-SY5Y cells (PMID:21290414)
• Repression of androgen receptor activity by HEYL, a third member of the Hairy/Enhancer-of-split-related family of Notch effectors. (PMID:21454491)
• repression of TGFbeta signaling by Notch acting through HEYL may promote initiation of breast cancer (PMID:25217524)
• LSD1 directly associates with the promoter of the HEYL gene. (PMID:27018646)
• HEYL rs784621 AA genotype is associated with poor response to therapy in Non-small Cell Lung Cancer. (PMID:28766235)
• Elevated HEYL expression is associated with metastatic colorectal cancer. (PMID:31796022)
• The NOTCH3 Downstream Target HEYL Is Required for Efficient Human Airway Basal Cell Differentiation. (PMID:34831437)
• Partial-Methylated HeyL Promoter Predicts the Severe Illness in Egyptian COVID-19 Patients. (PMID:35655915)
• Notch3 regulates Mybl2 via HeyL to limit proliferation and tumor initiation in breast cancer. (PMID:36854682)
• Hypercoagulability evaluation in congenital red blood cell disorders using thrombin generation assay. (PMID:37024320)

Cross-species orthologs

21 orthologs

Organism	Symbol	Gene ID
danio_rerio	her4.4	ENSDARG00000009822
danio_rerio	her7	ENSDARG00000017917
danio_rerio	heyl	ENSDARG00000055798
danio_rerio	her4.5	ENSDARG00000056729
danio_rerio	her4.1	ENSDARG00000056732
danio_rerio	her4.3	ENSDARG00000070770
danio_rerio	her4.2	ENSDARG00000094426
mus_musculus	Heyl	ENSMUSG00000032744
rattus_norvegicus	Heyl	ENSRNOG00000015318
drosophila_melanogaster	E(spl)m8-HLH	FBGN0000591
drosophila_melanogaster	hry	FBGN0001168
drosophila_melanogaster	E(spl)m3-HLH	FBGN0002609
drosophila_melanogaster	E(spl)m5-HLH	FBGN0002631
drosophila_melanogaster	E(spl)m7-HLH	FBGN0002633
drosophila_melanogaster	E(spl)mbeta-HLH	FBGN0002733
drosophila_melanogaster	E(spl)mdelta-HLH	FBGN0002734
drosophila_melanogaster	E(spl)mgamma-HLH	FBGN0002735
drosophila_melanogaster	dpn	FBGN0010109
drosophila_melanogaster	Hesr	FBGN0030899
drosophila_melanogaster	Sidpn	FBGN0032741
drosophila_melanogaster	cwo	FBGN0259938

Paralogs (12): HES2 (ENSG00000069812), HES1 (ENSG00000114315), BHLHE41 (ENSG00000123095), BHLHE40 (ENSG00000134107), HEY2 (ENSG00000135547), HES6 (ENSG00000144485), HEY1 (ENSG00000164683), HES3 (ENSG00000173673), HES7 (ENSG00000179111), HELT (ENSG00000187821), HES4 (ENSG00000188290), HES5 (ENSG00000197921)

Protein

Protein identifiers

Hairy/enhancer-of-split related with YRPW motif-like protein — Q9NQ87 (reviewed: Q9NQ87)

Alternative names: Class B basic helix-loop-helix protein 33, Hairy-related transcription factor 3

All UniProt accessions (1): Q9NQ87

UniProt curated annotations — full annotation on UniProt →

Function. Downstream effector of Notch signaling which may be required for cardiovascular development. Transcriptional repressor which binds preferentially to the canonical E box sequence 5’-CACGTG-3’. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6.

Subunit / interactions. Self-associates. Interacts with GATA4, GATA6, HES1, HEY1 and HEY2. Interacts with HDAC1, NCOR1 and SIN3A.

Subcellular location. Nucleus.

Induction. By activation of the Notch signaling pathway.

Similarity. Belongs to the HEY family.

RefSeq proteins (1): NP_055386* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003650	Orange_dom	Domain
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR050370	HES_HEY	Family

Pfam: PF00010, PF07527

UniProt features (9 total): region of interest 3, domain 2, compositionally biased region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQ87-F1	65.98	0.25

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-9013508	NOTCH3 Intracellular Domain Regulates Transcription
R-HSA-9762293	Regulation of CDH11 gene transcription

MSigDB gene sets: 225 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, REACTOME_SIGNALING_BY_NOTCH, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, MYOGENIN_Q6, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_ENDOCARDIAL_CUSHION_DEVELOPMENT, GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_REGULATION_OF_INTRACELLULAR_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEUROGENESIS

GO Biological Process (28): outflow tract morphogenesis (GO:0003151), aortic valve morphogenesis (GO:0003180), atrioventricular valve morphogenesis (GO:0003181), pulmonary valve morphogenesis (GO:0003184), epithelial to mesenchymal transition involved in endocardial cushion formation (GO:0003198), endocardial cushion morphogenesis (GO:0003203), cardiac ventricle morphogenesis (GO:0003208), regulation of transcription by RNA polymerase II (GO:0006357), Notch signaling pathway (GO:0007219), anterior/posterior pattern specification (GO:0009952), negative regulation of gene expression (GO:0010629), mesenchymal cell development (GO:0014031), glomerulus development (GO:0032835), skeletal muscle cell differentiation (GO:0035914), obsolete negative regulation of DNA-binding transcription factor activity (GO:0043433), positive regulation of neuron differentiation (GO:0045666), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of neurogenesis (GO:0050767), cardiac epithelial to mesenchymal transition (GO:0060317), ventricular septum morphogenesis (GO:0060412), negative regulation of androgen receptor signaling pathway (GO:0060766), cellular response to BMP stimulus (GO:0071773), proximal tubule development (GO:0072014), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), anatomical structure morphogenesis (GO:0009653), circulatory system development (GO:0072359)

GO Molecular Function (11): 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 transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), protein homodimerization activity (GO:0042803), AF-1 domain binding (GO:0050683), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), protein dimerization activity (GO:0046983)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by NOTCH1	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Signaling by NOTCH3	1
Regulation of CDH11 Expression and Function	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
heart morphogenesis	3
heart valve morphogenesis	3
regulation of DNA-templated transcription	3
cellular anatomical structure	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
anatomical structure morphogenesis	1
aortic valve development	1
atrioventricular valve development	1
pulmonary valve development	1
endocardial cushion formation	1
cardiac epithelial to mesenchymal transition	1
endocardial cushion development	1
mesenchyme morphogenesis	1
cardiac chamber morphogenesis	1
cardiac ventricle development	1
cell surface receptor signaling pathway	1
regionalization	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
cell development	1
mesenchymal cell differentiation	1
anatomical structure development	1
nephron development	1
skeletal muscle tissue development	1
cell differentiation	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
neurogenesis	1
regulation of nervous system development	1
regulation of cell development	1
epithelial to mesenchymal transition	1
cis-regulatory region sequence-specific DNA binding	1

Protein interactions and networks

STRING

834 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HEYL	RBPJ	Q06330	696
HEYL	JAG1	P78504	676
HEYL	NOTCH3	Q9UM47	638
HEYL	DLL1	O00548	611
HEYL	NOTCH1	P46531	610
HEYL	NOTCH2	Q04721	608
HEYL	HES3	Q5TGS1	600
HEYL	DLL4	Q9NR61	599
HEYL	JAG2	Q9Y219	598
HEYL	NOTCH4	Q99466	573
HEYL	MAML1	Q92585	572
HEYL	MAML2	Q8IZL2	555
HEYL	MAML3	Q96JK9	548
HEYL	DLL3	Q9NYJ7	516
HEYL	HEY1	Q9Y5J3	473

IntAct

40 interactions, top by confidence:

A	B	Type	Score
HEYL	MDFI	psi-mi:“MI:0915”(physical association)	0.780
MDFI	HEYL	psi-mi:“MI:0915”(physical association)	0.780
RBPMS	HEYL	psi-mi:“MI:0915”(physical association)	0.670
HEYL	RBPMS	psi-mi:“MI:0915”(physical association)	0.670
HEYL	RPGRIP1	psi-mi:“MI:0915”(physical association)	0.560
RPGRIP1	HEYL	psi-mi:“MI:0915”(physical association)	0.560
BANP	HEYL	psi-mi:“MI:0915”(physical association)	0.560
PLEKHB2	HEYL	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-2	HEYL	psi-mi:“MI:0915”(physical association)	0.560
HEYL	PGGT1B	psi-mi:“MI:0914”(association)	0.530
HEYL	SP8	psi-mi:“MI:0915”(physical association)	0.370
CFTR	HEYL	psi-mi:“MI:0915”(physical association)	0.370
HEYL	ATXN1	psi-mi:“MI:0915”(physical association)	0.370
HEYL	HTT	psi-mi:“MI:0915”(physical association)	0.370
ZNF512B	HEYL	psi-mi:“MI:0915”(physical association)	0.370
SKIL	HEYL	psi-mi:“MI:0915”(physical association)	0.370
SMAD3	HEYL	psi-mi:“MI:0915”(physical association)	0.370
HIPK3	HEYL	psi-mi:“MI:0915”(physical association)	0.370
SMAD7	HEYL	psi-mi:“MI:0915”(physical association)	0.370
ATF7IP	HEYL	psi-mi:“MI:0915”(physical association)	0.370
HEYL	SMAD9	psi-mi:“MI:0915”(physical association)	0.370
LAPTM5	HEYL	psi-mi:“MI:0915”(physical association)	0.370
PPP1CA	HEYL	psi-mi:“MI:0915”(physical association)	0.370
HEYL	FNTA	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): HEYL (Two-hybrid), HEYL (Two-hybrid), RPGRIP1 (Two-hybrid), ARL10 (Affinity Capture-MS), FNTA (Affinity Capture-MS), PGGT1B (Affinity Capture-MS), HEYL (Two-hybrid), MDFI (Two-hybrid), FBXO45 (Affinity Capture-Western), PGGT1B (Affinity Capture-MS), ARL10 (Affinity Capture-MS), FNTA (Affinity Capture-MS), HEYL (Two-hybrid), HEYL (Two-hybrid), BANP (Two-hybrid)

ESM2 similar proteins: A8MTQ0, A9YTQ3, E1BEA8, O43763, O55087, O75360, O88940, P12980, P15863, P22091, P23683, P24899, P27792, P43688, P48985, P63156, P63157, P70061, P82976, Q02080, Q12870, Q12950, Q2NL18, Q3SYB3, Q5IS58, Q5RJB0, Q5VV16, Q60539, Q60756, Q61663, Q64124, Q66HH3, Q6VB84, Q6XD76, Q7RTS1, Q7RTU0, Q7RTU5, Q7RTU7, Q8AXV5, Q8BGW3

Diamond homologs: A0MLS5, A6NFD8, O00327, O02219, O02748, O08785, O15516, O15945, O61734, O88529, P27540, P41739, P53762, P79832, P90953, P97460, Q2NL18, Q2VPD4, Q5R4T2, Q5RAK8, Q5ZQU2, Q61324, Q6YGZ4, Q6YGZ5, Q78E60, Q7TS99, Q8BGD7, Q8IUM7, Q8QGQ6, Q8QGQ7, Q8WYA1, Q91YA8, Q91YA9, Q91YB0, Q91YB2, Q99743, Q9BE97, Q9DBX7, Q9DG12, Q9EPW1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NOTCH	“up-regulates quantity by expression”	HEYL	“transcriptional regulation”
NOTCH1	“up-regulates quantity by expression”	HEYL	“transcriptional regulation”
NOTCH3	“up-regulates quantity by expression”	HEYL	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
transforming growth factor beta receptor signaling pathway	5	36.1×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

711 predictions. Top by Δscore:

Variant	Effect	Δscore
1:39631492:ATACC:A	donor_loss	1.0000
1:39631493:TAC:T	donor_loss	1.0000
1:39631494:A:AC	donor_gain	1.0000
1:39631495:C:CC	donor_gain	1.0000
1:39631495:C:CG	donor_loss	1.0000
1:39631575:ATGAT:A	acceptor_gain	1.0000
1:39631576:TGAT:T	acceptor_gain	1.0000
1:39631577:GAT:G	acceptor_gain	1.0000
1:39631577:GATC:G	acceptor_loss	1.0000
1:39631577:GATCT:G	acceptor_gain	1.0000
1:39631578:AT:A	acceptor_gain	1.0000
1:39631578:ATCT:A	acceptor_gain	1.0000
1:39631580:C:CC	acceptor_gain	1.0000
1:39631581:T:A	acceptor_gain	1.0000
1:39632644:CTCA:C	donor_loss	1.0000
1:39632645:TCAC:T	donor_loss	1.0000
1:39632646:C:CG	donor_loss	1.0000
1:39632647:A:AC	donor_gain	1.0000
1:39632647:A:T	donor_loss	1.0000
1:39632647:AC:A	donor_gain	1.0000
1:39632647:ACC:A	donor_gain	1.0000
1:39632648:C:CC	donor_gain	1.0000
1:39632648:C:CT	donor_loss	1.0000
1:39632648:CC:C	donor_gain	1.0000
1:39632648:CCC:C	donor_gain	1.0000
1:39632648:CCCCT:C	donor_gain	1.0000
1:39632663:T:TA	donor_gain	1.0000
1:39632712:CTGG:C	acceptor_gain	1.0000
1:39632713:TGG:T	acceptor_gain	1.0000
1:39632716:C:CC	acceptor_gain	1.0000

AlphaMissense

2095 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:39627122:G:C	C124W	0.999
1:39627124:A:G	C124R	0.998
1:39627131:A:C	F121L	0.998
1:39627131:A:T	F121L	0.998
1:39627132:A:G	F121S	0.998
1:39627133:A:G	F121L	0.998
1:39627135:C:T	G120D	0.998
1:39627036:A:G	L153P	0.997
1:39627120:A:G	L125P	0.997
1:39627048:A:G	L149P	0.996
1:39627036:A:T	L153H	0.995
1:39627040:G:C	H152D	0.995
1:39627123:C:T	C124Y	0.995
1:39627136:C:G	G120R	0.995
1:39627132:A:C	F121C	0.994
1:39630289:T:A	K84I	0.994
1:39630277:A:G	L88S	0.993
1:39627048:A:T	L149H	0.992
1:39627129:C:G	R122P	0.991
1:39627135:C:A	G120V	0.991
1:39630288:T:A	K84N	0.991
1:39630288:T:G	K84N	0.991
1:39631551:A:G	I59T	0.991
1:39627039:T:G	H152P	0.990
1:39627111:A:T	V128D	0.990
1:39627103:A:C	Y131D	0.988
1:39630290:T:G	K84Q	0.988
1:39630292:T:A	E83V	0.987
1:39631554:C:G	R58P	0.987
1:39627123:C:A	C124F	0.986

dbSNP variants (sampled 300 via entrez): RS1000031229 (1:39634341 C>G,T), RS1000142660 (1:39631787 A>T), RS1000416735 (1:39638535 T>C), RS1000425551 (1:39631950 A>G), RS1000501791 (1:39640220 C>T), RS1001023752 (1:39636643 G>A), RS1001198531 (1:39633929 G>A,C), RS1001351203 (1:39641089 C>G), RS1001754059 (1:39638465 A>G), RS1002478807 (1:39636098 G>C), RS1002716050 (1:39625410 G>A,C), RS1002759519 (1:39629193 C>T), RS1002763150 (1:39636502 GTGA>G), RS1002902324 (1:39632440 T>A), RS1003052682 (1:39639779 C>A,T)

Disease associations

OMIM: gene MIM:609034 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001765_33	Red blood cell traits	3.000000e-10
GCST008070_107	HDL cholesterol levels	3.000000e-06
GCST008070_131	HDL cholesterol levels	5.000000e-07
GCST008070_63	HDL cholesterol levels	6.000000e-15
GCST008074_90	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	9.000000e-06
GCST008075_172	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-24
GCST008075_224	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-07
GCST008075_37	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5.000000e-17
GCST008083_102	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-06
GCST008084_122	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-07
GCST008084_219	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-27
GCST008084_49	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-17
GCST008085_146	HDL cholesterol levels in current drinkers	4.000000e-11
GCST008085_3	HDL cholesterol levels in current drinkers	2.000000e-06
GCST008085_66	HDL cholesterol levels in current drinkers	5.000000e-17

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004329	alcohol drinking

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	increases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	decreases expression, affects cotreatment	1
Vorinostat	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7RB	Ubigene A-549 HEYL KO	Cancer cell line	Male
CVCL_D8MD	Ubigene HCT 116 HEYL KO	Cancer cell line	Male
CVCL_D9G8	Ubigene HEK293 HEYL KO	Transformed cell line	Female

Clinical trials (associated diseases)

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