GAR1

Summary

GAR1 (GAR1 ribonucleoprotein, HGNC:14264) is a protein-coding gene on chromosome 4q25, encoding H/ACA ribonucleoprotein complex subunit 1 (Q9NY12). Required for ribosome biogenesis and telomere maintenance. It is a selective cancer dependency (DepMap: 60.3% of cell lines).

This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the DKC1, NOLA2 and NOLA3 proteins. These four H/ACA snoRNP proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. These four H/ACA snoRNP proteins are also components of the telomerase complex. The encoded protein of this gene contains two glycine- and arginine-rich domains and is related to Saccharomyces cerevisiae Gar1p. Two splice variants have been found for this gene.

Source: NCBI Gene 54433 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 33 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 60.3% of screened cell lines
• MANE Select transcript: NM_018983

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14264
Approved symbol	GAR1
Name	GAR1 ribonucleoprotein
Location	4q25
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000109534
Ensembl biotype	protein_coding
OMIM	606468
Entrez	54433

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 18 protein_coding, 2 retained_intron

ENST00000226796, ENST00000394631, ENST00000503671, ENST00000506840, ENST00000863519, ENST00000863520, ENST00000863521, ENST00000863522, ENST00000863523, ENST00000863524, ENST00000863525, ENST00000939229, ENST00000939230, ENST00000939231, ENST00000939232, ENST00000939233, ENST00000939234, ENST00000939235, ENST00000958032, ENST00000958033

RefSeq mRNA: 2 — MANE Select: NM_018983 NM_018983, NM_032993

CCDS: CCDS34050

Canonical transcript exons

ENST00000226796 — 7 exons

Exon	Start	End
ENSE00000736617	109822347	109822488
ENSE00000841714	109823965	109824033
ENSE00001672268	109815762	109815804
ENSE00002078448	109824418	109824737
ENSE00003586749	109819001	109819060
ENSE00003642391	109816153	109816378
ENSE00003666186	109817936	109818090

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 97.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.6719 / max 421.0361, expressed in 1820 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49241	27.3394	1807
49242	7.2989	1642
49243	0.8558	552
49240	0.6145	386
49244	0.3184	110
203311	0.2449	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	97.85	gold quality
parotid gland	UBERON:0001831	95.83	gold quality
amniotic fluid	UBERON:0000173	95.65	gold quality
esophagus squamous epithelium	UBERON:0006920	95.31	gold quality
medial globus pallidus	UBERON:0002477	94.57	gold quality
epithelium of esophagus	UBERON:0001976	94.47	gold quality
squamous epithelium	UBERON:0006914	93.84	gold quality
germinal epithelium of ovary	UBERON:0001304	93.79	gold quality
epithelium of nasopharynx	UBERON:0001951	93.65	gold quality
endometrium	UBERON:0001295	92.98	gold quality
globus pallidus	UBERON:0001875	92.75	gold quality
hair follicle	UBERON:0002073	92.68	silver quality
gingival epithelium	UBERON:0001949	92.49	gold quality
cervix squamous epithelium	UBERON:0006922	92.48	silver quality
oral cavity	UBERON:0000167	92.23	gold quality
gingiva	UBERON:0001828	92.10	gold quality
parietal pleura	UBERON:0002400	92.08	gold quality
visceral pleura	UBERON:0002401	91.82	gold quality
pleura	UBERON:0000977	91.60	gold quality
monocyte	CL:0000576	91.54	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.44	gold quality
mononuclear cell	CL:0000842	91.27	gold quality
secondary oocyte	CL:0000655	91.14	gold quality
pharyngeal mucosa	UBERON:0000355	91.11	gold quality
tibia	UBERON:0000979	91.10	gold quality
leukocyte	CL:0000738	90.92	gold quality
colonic mucosa	UBERON:0000317	90.79	gold quality
mucosa of transverse colon	UBERON:0004991	90.62	gold quality
bronchial epithelial cell	CL:0002328	90.47	gold quality
nipple	UBERON:0002030	90.44	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	8.75
E-ANND-3	yes	6.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting GAR1, 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-607	99.97	73.62	5593
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-657	99.48	66.02	848
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-3977	98.00	68.17	1500

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 60.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• heterozygous point mutations in NOLA1 gene are not responsible for aplastic anemia in our patients at least acting via telomere (PMID:18989882)
• The box H/ACA ribonucleoprotein complex: interplay of RNA and protein structures in post-transcriptional RNA modification. (PMID:19917616)
• The deregulated expression and function of H/ACA snoRNPs may underlie specific pathological features of human disease. (PMID:23707062)
• SUMOylation- and GAR1-Dependent Regulation of Dyskerin Nuclear and Subnuclear Localization. (PMID:33526451)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gar1	ENSDARG00000076526
mus_musculus	Gar1	ENSMUSG00000028010
rattus_norvegicus	Gar1	ENSRNOG00000061146
drosophila_melanogaster	Gar1	FBGN0011824
caenorhabditis_elegans		WBGENE00022046

Protein

Protein identifiers

H/ACA ribonucleoprotein complex subunit 1 — Q9NY12 (reviewed: Q9NY12)

Alternative names: Nucleolar protein family A member 1, snoRNP protein GAR1

All UniProt accessions (1): Q9NY12

UniProt curated annotations — full annotation on UniProt →

Function. Required for ribosome biogenesis and telomere maintenance. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine (‘psi’) residues, which may serve to stabilize the conformation of rRNAs. May also be required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme.

Subunit / interactions. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which contains NHP2/NOLA2, GAR1/NOLA1, NOP10/NOLA3, and DKC1/NOLA4, which is presumed to be the catalytic subunit. The complex contains a stable core formed by binding of one or two NOP10-DKC1 heterodimers to NHP2; GAR1 subsequently binds to this core via DKC1. The complex binds a box H/ACA small nucleolar RNA (snoRNA), which may target the specific site of modification within the RNA substrate. The complex also interacts with TERC, which contains a 3’-terminal domain related to the box H/ACA snoRNAs. Specific interactions with snoRNAs or TERC are mediated by GAR1 and NHP2. Associates with NOLC1/NOPP140. H/ACA snoRNPs interact with the SMN complex, consisting of SMN1 or SMN2, GEMIN2/SIP1, DDX20/GEMIN3, and GEMIN4. This is mediated by interaction between GAR1 and SMN1 or SMN2. The SMN complex may be required for correct assembly of the H/ACA snoRNP complex. Component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1.

Subcellular location. Nucleus. Nucleolus. Cajal body.

Domain organisation. Interaction with SMN1 requires at least one of the RGG-box regions.

Similarity. Belongs to the GAR1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NY12-1	1	yes
Q9NY12-2	2

RefSeq proteins (2): NP_061856, NP_127460 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007504	H/ACA_rnp_Gar1/Naf1	Family
IPR009000	Transl_B-barrel_sf	Homologous_superfamily
IPR038664	Gar1/Naf1_Cbf5-bd_sf	Homologous_superfamily

Pfam: PF04410

UniProt features (19 total): strand 5, region of interest 4, compositionally biased region 3, turn 2, chain 1, sequence conflict 1, helix 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8OUE	ELECTRON MICROSCOPY	2.7
9QB2	ELECTRON MICROSCOPY	3
8OUF	ELECTRON MICROSCOPY	3.1
7TRC	ELECTRON MICROSCOPY	3.3
7BGB	ELECTRON MICROSCOPY	3.4
9QB3	ELECTRON MICROSCOPY	3.9
7V9A	ELECTRON MICROSCOPY	3.94

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NY12-F1	66.21	0.21

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 (1): 134

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-171319	Telomere Extension By Telomerase
R-HSA-6790901	rRNA modification in the nucleus and cytosol

MSigDB gene sets: 172 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, chr4q25, GOBP_RIBOSOME_BIOGENESIS, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_PSEUDOURIDINE_SYNTHESIS, MUELLER_PLURINET, GOBP_RNA_MODIFICATION, GNF2_ANP32B, GNF2_SMC4L1

GO Biological Process (5): snoRNA guided rRNA pseudouridine synthesis (GO:0000454), telomere maintenance via telomerase (GO:0007004), pseudouridine synthesis (GO:0001522), rRNA processing (GO:0006364), ribosome biogenesis (GO:0042254)

GO Molecular Function (4): RNA binding (GO:0003723), box H/ACA snoRNA binding (GO:0034513), telomerase RNA binding (GO:0070034), protein binding (GO:0005515)

GO Cellular Component (11): chromosome, telomeric region (GO:0000781), fibrillar center (GO:0001650), nucleoplasm (GO:0005654), telomerase holoenzyme complex (GO:0005697), box H/ACA snoRNP complex (GO:0031429), box H/ACA scaRNP complex (GO:0072589), box H/ACA telomerase RNP complex (GO:0090661), nucleus (GO:0005634), nucleolus (GO:0005730), Cajal body (GO:0015030), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Extension of Telomeres	1
rRNA processing in the nucleus and cytosol	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear protein-containing complex	4
catalytic complex	3
box H/ACA RNP complex	3
nucleolus	2
cellular anatomical structure	2
nuclear lumen	2
rRNA pseudouridine synthesis	1
telomerase activity	1
RNA-templated DNA biosynthetic process	1
telomere maintenance via telomere lengthening	1
telomere-telomerase complex assembly	1
RNA modification	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
ribonucleoprotein complex biogenesis	1
nucleic acid binding	1
snoRNA binding	1
RNA binding	1
binding	1
chromosomal region	1
ribonucleoprotein complex	1
Cajal body	1
telomerase holoenzyme complex	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
nuclear ribonucleoprotein granule	1
protein-containing complex	1

Protein interactions and networks

STRING

2152 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GAR1	NHP2	Q9NX24	987
GAR1	NOP10	Q9NPE3	986
GAR1	DKC1	O60832	983
GAR1	SHQ1	Q6PI26	898
GAR1	FBL	P22087	883
GAR1	WRAP53	Q9BUR4	778
GAR1	TERT	O14746	720
GAR1	POLR1A	O95602	692
GAR1	PHAX	Q9H814	640
GAR1	SNU13	P55769	624
GAR1	NOP56	O00567	607
GAR1	POT1	Q9NUX5	604
GAR1	NOP58	Q9Y2X3	590
GAR1	NAF1	Q96HR8	575
GAR1	RUVBL1	P82276	555

IntAct

103 interactions, top by confidence:

A	B	Type	Score
NOP10	DKC1	psi-mi:“MI:0914”(association)	0.890
GAR1	DKC1	psi-mi:“MI:0914”(association)	0.790
DKC1	TERT	psi-mi:“MI:0915”(physical association)	0.750
SMN1	GAR1	psi-mi:“MI:0407”(direct interaction)	0.540
GAR1	SMN1	psi-mi:“MI:0915”(physical association)	0.540
GAR1	PRMT5	psi-mi:“MI:0914”(association)	0.530
KRR1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF71	DKC1	psi-mi:“MI:0914”(association)	0.530
HMBOX1	DKC1	psi-mi:“MI:0914”(association)	0.500
Snu13		psi-mi:“MI:0915”(physical association)	0.400
GAR1	TAF1	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
KSR1		psi-mi:“MI:0914”(association)	0.350
DLST		psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
USP10	EIF4G3	psi-mi:“MI:0914”(association)	0.350
USP39	RRP8	psi-mi:“MI:0914”(association)	0.350
BLK	HNRNPCL1	psi-mi:“MI:0914”(association)	0.350
PRKD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
ARHGAP36	HAX1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350

BioGRID (296): GAR1 (Affinity Capture-MS), GAR1 (Affinity Capture-MS), GAR1 (Affinity Capture-MS), NOP10 (Affinity Capture-MS), PRMT5 (Affinity Capture-MS), GEMIN5 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), RIOK1 (Affinity Capture-MS), SHQ1 (Affinity Capture-MS), CLNS1A (Affinity Capture-MS), WRAP53 (Affinity Capture-MS), COPRS (Affinity Capture-MS), GAR1 (Affinity Capture-MS), DKC1 (Co-fractionation), GAR1 (Co-fractionation)

ESM2 similar proteins: A0A2R8Y4L2, A1CVY3, A3GHP2, A5A6H4, A6SDR8, A7VJC2, O88569, P04256, P09651, P09867, P0CN78, P0CN79, P0DKK8, P0DKK9, P17130, P22626, P28007, P48810, P49312, P51968, P51989, P51990, P51991, P51992, Q06975, Q1E6M1, Q28521, Q2HH48, Q2HJ60, Q32P51, Q4P5P0, Q54XE6, Q5RBU8, Q5RJV1, Q61B10, Q6AYA1, Q6BVF9, Q6CJ45, Q6FSB0, Q6URK4

Diamond homologs: A1CVY3, A3GHP2, A6SDR8, O96722, P0CN78, P0CN79, P28007, Q06975, Q1E6M1, Q2HH48, Q4P5P0, Q54XE6, Q5RJV1, Q61B10, Q6AYA1, Q6BVF9, Q6CJ45, Q6FSB0, Q757V8, Q7KVQ0, Q7ZVE0, Q8VZT0, Q9CY66, Q9FK53, Q9NY12, Q9TYK1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GAR1	“up-regulates activity”	TERT	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
rRNA modification in the nucleus and cytosol	6	13.7×	9e-04
Response of EIF2AK4 (GCN2) to amino acid deficiency	8	10.8×	2e-04
Peptide chain elongation	6	9.3×	3e-03
Viral mRNA Translation	6	9.3×	3e-03
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	6	9.2×	3e-03
Transcriptional regulation by RUNX1	5	8.9×	7e-03
Selenocysteine synthesis	6	8.8×	3e-03
Eukaryotic Translation Termination	6	8.8×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal complex assembly	6	34.7×	2e-05
positive regulation of miRNA transcription	6	16.8×	4e-04
cytoplasmic translation	7	12.5×	4e-04
rRNA processing	8	10.9×	4e-04
translation	8	7.9×	2e-03
positive regulation of gene expression	11	4.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

899 predictions. Top by Δscore:

Variant	Effect	Δscore
4:109816370:GTGTA:G	donor_gain	1.0000
4:109817934:A:AG	acceptor_gain	1.0000
4:109817935:G:GG	acceptor_gain	1.0000
4:109822345:A:AG	acceptor_gain	1.0000
4:109822346:G:GA	acceptor_gain	1.0000
4:109822346:GT:G	acceptor_gain	1.0000
4:109822346:GTT:G	acceptor_gain	1.0000
4:109822346:GTTT:G	acceptor_gain	1.0000
4:109822346:GTTTT:G	acceptor_gain	1.0000
4:109822485:GGCG:G	donor_gain	1.0000
4:109822486:GCG:G	donor_gain	1.0000
4:109822486:GCGG:G	donor_gain	1.0000
4:109822487:CGG:C	donor_loss	1.0000
4:109822489:G:GG	donor_gain	1.0000
4:109822489:GTAA:G	donor_loss	1.0000
4:109822490:T:G	donor_loss	1.0000
4:109823963:AGGT:A	acceptor_gain	1.0000
4:109823963:AGGTG:A	acceptor_gain	1.0000
4:109823964:GGT:G	acceptor_gain	1.0000
4:109823964:GGTG:G	acceptor_gain	1.0000
4:109823964:GGTGG:G	acceptor_gain	1.0000
4:109824030:AGAGG:A	donor_loss	1.0000
4:109824031:GAG:G	donor_gain	1.0000
4:109824032:AG:A	donor_gain	1.0000
4:109824032:AGG:A	donor_loss	1.0000
4:109824033:GG:G	donor_gain	1.0000
4:109824034:G:GG	donor_gain	1.0000
4:109824034:GTG:G	donor_loss	1.0000
4:109816303:G:T	donor_gain	0.9900
4:109816319:G:GT	donor_gain	0.9900

AlphaMissense

1359 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:109817942:G:A	G74E	1.000
4:109817960:G:A	C80Y	1.000
4:109817961:T:G	C80W	1.000
4:109817972:T:A	I84K	1.000
4:109817975:T:A	V85D	1.000
4:109817977:T:C	C86R	1.000
4:109817979:T:G	C86W	1.000
4:109818007:C:T	P96S	1.000
4:109818008:C:A	P96H	1.000
4:109818010:T:G	Y97D	1.000
4:109818013:T:A	F98I	1.000
4:109818013:T:C	F98L	1.000
4:109818013:T:G	F98V	1.000
4:109818014:T:C	F98S	1.000
4:109818014:T:G	F98C	1.000
4:109818015:C:A	F98L	1.000
4:109818015:C:G	F98L	1.000
4:109818018:T:A	N99K	1.000
4:109818018:T:G	N99K	1.000
4:109818019:G:C	A100P	1.000
4:109818020:C:A	A100D	1.000
4:109818026:T:A	V102D	1.000
4:109818050:T:A	I110N	1.000
4:109818052:G:A	G111R	1.000
4:109818052:G:C	G111R	1.000
4:109818053:G:A	G111E	1.000
4:109818053:G:T	G111V	1.000
4:109818059:T:A	V113E	1.000
4:109818064:G:A	E115K	1.000
4:109818065:A:G	E115G	1.000

dbSNP variants (sampled 300 via entrez): RS1000272685 (4:109822468 G>C), RS1000340980 (4:109815376 T>C), RS10003826 (4:109818483 T>C,G), RS10004390 (4:109822037 G>A,C,T), RS1000662726 (4:109820667 G>C), RS1000678049 (4:109814288 A>C), RS1000728904 (4:109822135 A>C,G,T), RS1000895067 (4:109814761 T>G), RS1001271064 (4:109817140 A>G,T), RS1002273437 (4:109818477 C>G), RS1002509582 (4:109824241 T>G), RS1002659900 (4:109817309 A>G), RS10026711 (4:109822156 A>T), RS1004228008 (4:109822857 C>T), RS1004572780 (4:109814998 G>A)

Disease associations

OMIM: gene MIM:606468 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000089_1	Exercise treadmill test traits	3.000000e-06
GCST002248_6	Fasting insulin (dietary factor interaction)	9.000000e-06
GCST002253_4	Homeostasis model assessment of insulin resistance (dietary factor interaction)	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004328	exercise test
EFO:0008111	diet measurement
EFO:0004501	HOMA-IR

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067293 (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
6.74	Kd	181.2	nM	CHEMBL3752910
6.74	ED50	181.2	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	2148416: Binding affinity to human GAR1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1812	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression, affects expression, decreases expression	3
Acetaminophen	decreases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Hydrogen Peroxide	affects expression	2
Valproic Acid	affects expression, decreases methylation	2
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
trichostatin A	affects expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression, affects cotreatment	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Rosiglitazone	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Ozone	increases expression	1
Piroxicam	decreases expression	1
Progesterone	decreases expression	1
Ribonucleotides	affects binding	1
Silicon Dioxide	increases expression	1
Cyclosporine	increases expression	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
CHEMBL5651458	Binding	Binding affinity to human GAR1 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.