LYAR

Summary

LYAR (Ly1 antibody reactive, HGNC:26021) is a protein-coding gene on chromosome 4p16.3, encoding Cell growth-regulating nucleolar protein (Q9NX58). Plays a role in the maintenance of the appropriate processing of 47S/45S pre-rRNA to 32S/30S pre-rRNAs and their subsequent processing to produce 18S and 28S rRNAs.

Enables several functions, including DNA-binding transcription factor binding activity; identical protein binding activity; and transcription regulator inhibitor activity. Involved in several processes, including erythrocyte development; negative regulation of innate immune response; and regulation of DNA-templated transcription. Located in nucleolus and nucleoplasm.

Source: NCBI Gene 55646 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 83 total
• Druggable target: yes
• MANE Select transcript: NM_017816

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26021
Approved symbol	LYAR
Name	Ly1 antibody reactive
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	ZLYAR
Ensembl gene	ENSG00000145220
Ensembl biotype	protein_coding
OMIM	617684
Entrez	55646

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000343470, ENST00000452476, ENST00000502917, ENST00000513174, ENST00000870346, ENST00000936323, ENST00000936324, ENST00000936325, ENST00000936326, ENST00000936327, ENST00000936328, ENST00000945723

RefSeq mRNA: 2 — MANE Select: NM_017816 NM_001145725, NM_017816

CCDS: CCDS3374

Canonical transcript exons

ENST00000343470 — 10 exons

Exon	Start	End
ENSE00000969403	4279642	4279749
ENSE00000969404	4279447	4279530
ENSE00000969405	4274367	4274769
ENSE00000969406	4273583	4273669
ENSE00000969407	4268530	4268615
ENSE00001221464	4286519	4286572
ENSE00001221477	4283621	4283795
ENSE00001306099	4290036	4290154
ENSE00003542087	4267701	4268023
ENSE00003791114	4281783	4281897

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 99.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.0082 / max 288.6674, expressed in 1811 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51190	24.5277	1810
51189	3.1729	1116
51188	0.1403	60
51187	0.1377	29
51185	0.0148	4
51186	0.0147	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.33	gold quality
oocyte	CL:0000023	98.27	gold quality
left testis	UBERON:0004533	96.79	gold quality
sperm	CL:0000019	96.63	gold quality
right testis	UBERON:0004534	96.19	gold quality
testis	UBERON:0000473	95.64	gold quality
granulocyte	CL:0000094	94.33	gold quality
tendon of biceps brachii	UBERON:0008188	94.33	gold quality
adult organism	UBERON:0007023	93.61	gold quality
leukocyte	CL:0000738	91.79	gold quality
monocyte	CL:0000576	91.64	gold quality
tendon	UBERON:0000043	90.24	gold quality
pericardium	UBERON:0002407	89.94	gold quality
lymph node	UBERON:0000029	89.68	gold quality
left ventricle myocardium	UBERON:0006566	89.61	silver quality
spleen	UBERON:0002106	89.14	gold quality
calcaneal tendon	UBERON:0003701	88.51	gold quality
vermiform appendix	UBERON:0001154	88.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.08	gold quality
blood	UBERON:0000178	87.96	gold quality
pancreatic ductal cell	CL:0002079	87.92	silver quality
caecum	UBERON:0001153	87.58	gold quality
gastrocnemius	UBERON:0001388	87.43	gold quality
myocardium	UBERON:0002349	87.35	silver quality
muscle of leg	UBERON:0001383	87.10	gold quality
pharyngeal mucosa	UBERON:0000355	86.85	gold quality
buccal mucosa cell	CL:0002336	86.47	gold quality
peritoneum	UBERON:0002358	86.10	gold quality
omental fat pad	UBERON:0010414	86.08	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-8207	yes	539.27
E-GEOD-149689	yes	469.83
E-GEOD-139324	yes	417.68
E-MTAB-9221	yes	364.94
E-HCAD-4	yes	154.28
E-HCAD-6	yes	51.50
E-HCAD-8	yes	48.49
E-CURD-122	yes	46.39
E-HCAD-1	yes	41.82
E-CURD-88	yes	37.68
E-MTAB-10042	yes	14.15
E-CURD-46	yes	11.63
E-CURD-112	yes	8.54
E-MTAB-8911	no	578.85
E-GEOD-106540	no	572.44

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
IRF3	Repression

miRNA regulators (miRDB)

13 targeting LYAR, 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-1277-5P	100.00	73.95	5056
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-4776-5P	97.14	66.63	405

Literature-anchored findings (GeneRIF, showing 10)

• Over-expression of LYAR increases cell proliferation without affecting the expression of c-Myc or p53. Some rapidly growing cells enhance ribosome biogenesis by increasing the expression of LYAR. (PMID:24495227)
• Results show that LYAR protein expression is testis-predominant but can also be found in cancer cells originated from tissues other than testis. Lyar seems to promote proliferation of NIH-3T3 cells. (PMID:24990247)
• The data indicate that LYAR acts as a novel transcription factor that binds the gamma-globin gene, and is essential for silencing the gamma-globin gene. (PMID:25092918)
• LYAR may promote tumor cell migration and invasion by upregulating galectin-1 gene expression in colorectal cancer. (PMID:26413750)
• Data suggest that LYAR induces proliferation and promotes survival of neuroblastoma cells by repressing the expression of oxidative stress genes such as CHAC1 and suppressing oxidative stress, and identify LYAR as a novel co-factor in N-Myc oncogenesis. (PMID:28686580)
• Ly1 antibody reactive cell growth-regulating nucleolar protein (LYAR) expression is induced by beta interferon (IFN-beta) during virus infection. LYAR interacts with phosphorylated IFN regulatory factor 3 (IRF3) to impede the DNA binding capacity of IRF3, thereby suppressing the transcription of IFN-beta and downstream IFN-stimulated genes (ISGs). LYAR is a repressor of host innate immune responses to promote virus rep… (PMID:31413131)
• These data suggest that LYAR promotes the association of the BRD2-KAT7 and BRD4-KAT7 complexes with transcription-competent rDNA loci but not to transcriptionally silent rDNA loci, thereby increasing rRNA synthesis by altering the local acetylation status of histone H3 and H4. (PMID:31504794)
• Analysis of the role of Ly-1 antibody reactive in different cancer types. (PMID:34696677)
• LYAR promotes the proliferation of non-small cell lung cancer and is associated with poor prognosis. (PMID:34890041)
• The rs368698783 (G>A) Polymorphism Affecting LYAR Binding to the Agamma-Globin Gene Is Associated with High Fetal Hemoglobin (HbF) in beta-Thalassemia Erythroid Precursor Cells Treated with HbF Inducers. (PMID:36614221)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lyar	ENSDARG00000098507
mus_musculus	Lyar	ENSMUSG00000067367
rattus_norvegicus	Lyar	ENSRNOG00000005374
drosophila_melanogaster	CG12909	FBGN0033507
caenorhabditis_elegans		WBGENE00007628

Protein

Protein identifiers

Cell growth-regulating nucleolar protein — Q9NX58 (reviewed: Q9NX58)

All UniProt accessions (2): D6RDJ1, Q9NX58

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the maintenance of the appropriate processing of 47S/45S pre-rRNA to 32S/30S pre-rRNAs and their subsequent processing to produce 18S and 28S rRNAs. Also acts at the level of transcription regulation. Along with PRMT5, binds the gamma-globin (HBG1/HBG2) promoter and represses its expression. In neuroblastoma cells, may also repress the expression of oxidative stress genes, including CHAC1, HMOX1, SLC7A11, ULBP1 and SNORD41 that encodes a small nucleolar RNA. Preferentially binds to a DNA motif containing 5’-GGTTAT-3’. Negatively regulates the antiviral innate immune response by targeting IRF3 and impairing its DNA-binding activity. In addition, inhibits NF-kappa-B-mediated expression of pro-inflammatory cytokines. Stimulates phagocytosis of photoreceptor outer segments by retinal pigment epithelial cells. Prevents nucleolin/NCL self-cleavage, maintaining a normal steady-state level of NCL protein in undifferentiated embryonic stem cells (ESCs), which in turn is essential for ESC self-renewal.

Subunit / interactions. Interacts with PRMT5; this interaction is direct. Interacts with GNL2 and RPL23A. Interacts with nucleolin/NCL; this interaction is direct. Interacts with phosphorylated IRF3; this interaction impairs IRF3 DNA-binding activity.

Subcellular location. Nucleus. Nucleolus. Cytoplasm. Cell projection. Cilium. Photoreceptor outer segment.

Tissue specificity. Predominantly expressed in testis.

Domain organisation. The N-terminal zinc-finger domains are required for the appropriate production of 28S rRNA and the formation of pre-60S particles.

Induction. Induced by MYCN. Induced by interferon-beta.

RefSeq proteins (2): NP_001139197, NP_060286* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR014898	Znf_C2H2_LYAR	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR039999	LYAR	Family
IPR041010	Znf-ACC	Domain
IPR058719	WHD_LYAR	Domain

Pfam: PF08790, PF17848, PF25879

UniProt features (33 total): binding site 8, compositionally biased region 5, helix 4, strand 3, zinc finger region 2, modified residue 2, cross-link 2, sequence variant 2, chain 1, mutagenesis site 1, sequence conflict 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6ZMI	ELECTRON MICROSCOPY	2.6
6ZVH	ELECTRON MICROSCOPY	2.9
6ZMO	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NX58-F1	70.88	0.31

Functional residue map

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

Ligand- & substrate-binding residues (8): 6; 9; 21; 25; 33; 36; 48; 51

Post-translational modifications (4): 215, 244, 14, 207

Mutagenesis-validated functional residues (1):

Position	Phenotype
1–58	decreases the production of 28s rrna and the formation of pre-60s particle.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 210 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_BCELL_DN, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_MYELOID_CELL_HOMEOSTASIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_MYELOID_CELL_DEVELOPMENT, CMYB_01, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), rRNA processing (GO:0006364), innate immune response (GO:0045087), negative regulation of innate immune response (GO:0045824), positive regulation of transcription by RNA polymerase I (GO:0045943), erythrocyte development (GO:0048821), positive regulation of phagocytosis (GO:0050766), immune system process (GO:0002376)

GO Molecular Function (8): DNA binding (GO:0003677), RNA binding (GO:0003723), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), DNA-binding transcription factor binding (GO:0140297), transcription regulator inhibitor activity (GO:0140416), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): photoreceptor outer segment (GO:0001750), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
nucleic acid binding	2
nuclear lumen	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
immune response	1
defense response to symbiont	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
negative regulation of immune response	1
regulation of transcription by RNA polymerase I	1
transcription by RNA polymerase I	1
positive regulation of DNA-templated transcription	1
erythrocyte differentiation	1
myeloid cell development	1
phagocytosis	1
positive regulation of endocytosis	1
regulation of phagocytosis	1
biological_process	1
transition metal ion binding	1
protein binding	1
transcription factor binding	1
regulation of gene expression	1
transcription regulator activity	1
molecular function inhibitor activity	1
binding	1
cation binding	1
photoreceptor cell cilium	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYAR	NOP14	P78316	592
LYAR	PRMT5	O14744	513
LYAR	BRIX1	Q8TDN6	501
LYAR	BMS1	Q14692	461
LYAR	RRP1B	Q14684	459
LYAR	SNRPB2	P08579	450
LYAR	ZBTB49	Q6ZSB9	438
LYAR	DDX18	Q9NVP1	434
LYAR	NSRP1	Q9H0G5	428
LYAR	SNRPA1	P09661	428
LYAR	TSACC	Q96A04	424
LYAR	ESRP2	Q9H6T0	414
LYAR	TJP3	O95049	403
LYAR	FMR1	Q06787	403
LYAR	IFI16	Q16666	403
LYAR	TMEM128	Q5BJH2	403

IntAct

326 interactions, top by confidence:

A	B	Type	Score
LYAR	PRKRA	psi-mi:“MI:0915”(physical association)	0.800
PRKRA	LYAR	psi-mi:“MI:0915”(physical association)	0.800
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
SDCBP2	LYAR	psi-mi:“MI:0915”(physical association)	0.780
LYAR	SDCBP2	psi-mi:“MI:0915”(physical association)	0.780
N	LYAR	psi-mi:“MI:0915”(physical association)	0.770
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
LYAR	BEND7	psi-mi:“MI:0915”(physical association)	0.560
BEND7	LYAR	psi-mi:“MI:0915”(physical association)	0.560
SREK1IP1	LYAR	psi-mi:“MI:0915”(physical association)	0.560
LYAR	LYAR	psi-mi:“MI:0915”(physical association)	0.560
BEND7	LYAR	psi-mi:“MI:0915”(physical association)	0.550
MAGEB10	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL30	RRP8	psi-mi:“MI:0914”(association)	0.530
	LYAR	psi-mi:“MI:0915”(physical association)	0.500
FOXC2	LYAR	psi-mi:“MI:0915”(physical association)	0.400
BAZ1B	LYAR	psi-mi:“MI:0915”(physical association)	0.400
ARMCX2	LYAR	psi-mi:“MI:0915”(physical association)	0.400
LYAR	TERF1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (482): LYAR (Two-hybrid), LYAR (Two-hybrid), BEND7 (Two-hybrid), LYAR (Affinity Capture-MS), LYAR (Affinity Capture-MS), LYAR (Affinity Capture-MS), LYAR (Affinity Capture-MS), LYAR (Affinity Capture-MS), LYAR (Affinity Capture-MS), ERCC4 (Co-fractionation), LYAR (Co-fractionation), LYAR (Affinity Capture-MS), LYAR (Proximity Label-MS), LYAR (Two-hybrid), PRKRA (Two-hybrid)

ESM2 similar proteins: A4FV97, D4ACP5, O09130, O35144, O76021, P38432, P51612, Q01831, Q05CL8, Q08288, Q14684, Q15554, Q28G87, Q32LC1, Q58CQ0, Q58CQ5, Q5I0E6, Q5NC05, Q5NVA9, Q5R8S0, Q5RCE6, Q5RDL2, Q5SU73, Q5SXM2, Q5XI01, Q5ZJJ1, Q66H19, Q66H85, Q6AYK5, Q6IRU7, Q7TSG2, Q80UU1, Q8BJW7, Q8BVY0, Q8N163, Q8VDP4, Q8VID5, Q91VE6, Q91YK2, Q96AY2

Diamond homologs: A0A0A0LLY1, A0A0D1C8Z4, A4QUF0, A5A6H4, C0HFE5, D3Z4I3, M0R7T6, O14979, O22703, O43347, O64571, O80678, O94311, O94432, P04256, P09651, P09867, P10979, P48809, P49310, P49311, P49312, P52912, P60824, P60825, P60826, P70372, Q03250, Q03251, Q03878, Q04836, Q05966, Q08288, Q08473, Q09464, Q12926, Q14011, Q14103, Q28521, Q28GD4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 199 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Eukaryotic Translation Initiation	10	22.2×	4e-10
Cap-dependent Translation Initiation	10	22.2×	4e-10
SARS-CoV-1 modulates host translation machinery	10	22.2×	4e-10
Peptide chain elongation	24	21.9×	3e-24
Viral mRNA Translation	24	21.9×	3e-24
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	24	21.7×	3e-24
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	25	21.2×	1e-24
Formation of a pool of free 40S subunits	26	20.9×	2e-25

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	26	26.9×	2e-27
regulation of mRNA processing	5	24.8×	2e-04
spliceosomal complex assembly	6	20.2×	8e-05
ribosomal large subunit biogenesis	8	19.8×	1e-06
translation	28	16.1×	3e-23
ribosomal small subunit biogenesis	11	14.0×	9e-08
translational initiation	6	12.0×	1e-03
rRNA processing	14	11.1×	1e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1525 predictions. Top by Δscore:

Variant	Effect	Δscore
4:4268524:CCATA:C	donor_loss	1.0000
4:4268525:CATAC:C	donor_loss	1.0000
4:4268526:ATAC:A	donor_loss	1.0000
4:4268527:TAC:T	donor_loss	1.0000
4:4268541:G:C	donor_gain	1.0000
4:4274362:CTTA:C	donor_loss	1.0000
4:4274363:TTACC:T	donor_loss	1.0000
4:4274364:TACCT:T	donor_loss	1.0000
4:4274365:A:AC	donor_gain	1.0000
4:4274365:AC:A	donor_gain	1.0000
4:4274365:ACC:A	donor_loss	1.0000
4:4274365:ACCTT:A	donor_gain	1.0000
4:4274366:C:CA	donor_gain	1.0000
4:4274366:CC:C	donor_gain	1.0000
4:4274366:CCTT:C	donor_gain	1.0000
4:4274366:CCTTC:C	donor_gain	1.0000
4:4274775:CA:C	acceptor_gain	1.0000
4:4274776:A:C	acceptor_gain	1.0000
4:4274776:A:T	acceptor_gain	1.0000
4:4274777:T:C	acceptor_gain	1.0000
4:4274777:T:TC	acceptor_gain	1.0000
4:4274782:C:CT	acceptor_gain	1.0000
4:4274783:A:T	acceptor_gain	1.0000
4:4279441:ACTT:A	donor_loss	1.0000
4:4279442:CT:C	donor_loss	1.0000
4:4279443:TT:T	donor_loss	1.0000
4:4279444:T:TG	donor_loss	1.0000
4:4279445:A:AC	donor_gain	1.0000
4:4279445:AC:A	donor_loss	1.0000
4:4279445:ACG:A	donor_gain	1.0000

AlphaMissense

2555 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:4279527:A:G	W117R	0.998
4:4279527:A:T	W117R	0.998
4:4279667:A:T	V107D	0.998
4:4279476:A:G	W134R	0.997
4:4279476:A:T	W134R	0.997
4:4279646:A:G	F114S	0.997
4:4281791:A:G	W77R	0.997
4:4281791:A:T	W77R	0.997
4:4281869:A:G	C51R	0.997
4:4283646:A:G	C33R	0.997
4:4283727:A:G	C6R	0.997
4:4283731:A:C	F4L	0.997
4:4283731:A:T	F4L	0.997
4:4283733:A:G	F4L	0.997
4:4279525:C:A	W117C	0.996
4:4279525:C:G	W117C	0.996
4:4279660:C:A	R109S	0.996
4:4279660:C:G	R109S	0.996
4:4279664:G:T	P108H	0.996
4:4279665:G:A	P108S	0.996
4:4283623:G:C	F40L	0.996
4:4283623:G:T	F40L	0.996
4:4283625:A:G	F40L	0.996
4:4283732:A:G	F4S	0.996
4:4268604:A:G	W311R	0.995
4:4268604:A:T	W311R	0.995
4:4279526:C:G	W117S	0.995
4:4279645:A:C	F114L	0.995
4:4279645:A:T	F114L	0.995
4:4279647:A:G	F114L	0.995

dbSNP variants (sampled 300 via entrez): RS1000033386 (4:4282069 A>T), RS1000159393 (4:4292113 C>G), RS1000296031 (4:4276395 C>T), RS1000408128 (4:4267322 CG>C), RS1000466940 (4:4291941 C>T), RS1000497713 (4:4291134 G>T), RS1000545760 (4:4281712 T>C), RS10006514 (4:4283998 C>T), RS1000672259 (4:4286868 G>A,C), RS1000830993 (4:4287031 G>A,C), RS1000893948 (4:4271355 T>A), RS1000973280 (4:4271572 G>C), RS1001012978 (4:4271795 T>G), RS10011220 (4:4284272 A>C,G), RS1001198724 (4:4276753 G>A,T)

Disease associations

OMIM: gene MIM:617684 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005359_10	Disease progression in age-related macular degeneration	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067332 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.36	Kd	4373	nM	CHEMBL3752910
5.36	ED50	4373	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149882: Binding affinity to human LYAR incubated for 45 mins by Kinobead based pull down assay	kd	4.3728	uM

CTD chemical–gene interactions

64 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation	4
Estradiol	increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Air Pollutants	increases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases expression	2
Copper	affects binding, decreases expression	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	increases expression, affects expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
Particulate Matter	increases abundance, increases expression	2
GSK-J4	increases expression	1
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	increases expression	1
deoxynivalenol	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
beta-methylcholine	affects expression	1
azoxystrobin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
ICG 001	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652924	Binding	Binding affinity to human LYAR incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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