HEATR1

Summary

HEATR1 (HEAT repeat containing 1, HGNC:25517) is a protein-coding gene on chromosome 1q43, encoding HEAT repeat-containing protein 1 (Q9H583). Ribosome biogenesis factor; required for recruitment of Myc to nucleoli. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

Enables RNA binding activity. Involved in several processes, including positive regulation of RNA metabolic process; protein localization to nucleolus; and ribosomal small subunit biogenesis. Located in fibrillar center and mitochondrion. Part of small-subunit processome. Implicated in pancreatic ductal carcinoma. Biomarker of glioblastoma.

Source: NCBI Gene 55127 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 407 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_018072

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25517
Approved symbol	HEATR1
Name	HEAT repeat containing 1
Location	1q43
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10359, BAP28, UTP10
Ensembl gene	ENSG00000119285
Ensembl biotype	protein_coding
OMIM	620390
Entrez	55127

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000366579, ENST00000366581, ENST00000366582, ENST00000483073, ENST00000490339, ENST00000927216

RefSeq mRNA: 1 — MANE Select: NM_018072 NM_018072

CCDS: CCDS31066

Canonical transcript exons

ENST00000366582 — 45 exons

Exon	Start	End
ENSE00000793508	236551999	236552107
ENSE00000793509	236553581	236553739
ENSE00000793510	236554598	236554752
ENSE00000793511	236555296	236555464
ENSE00000793512	236555551	236555655
ENSE00000793513	236555805	236555939
ENSE00000805390	236556100	236556258
ENSE00000908031	236564498	236564661
ENSE00000908032	236565919	236566045
ENSE00000908033	236566646	236566876
ENSE00000908034	236568996	236569124
ENSE00000908035	236571351	236571472
ENSE00000908036	236571568	236571686
ENSE00000908037	236572411	236572554
ENSE00000908038	236572725	236572828
ENSE00000908039	236574202	236574333
ENSE00000908040	236574661	236574903
ENSE00000908041	236576219	236576377
ENSE00000908042	236576780	236576949
ENSE00000908043	236581222	236581414
ENSE00000908044	236582736	236582872
ENSE00000908045	236583013	236583196
ENSE00000908047	236585820	236585941
ENSE00000908048	236586241	236586452
ENSE00000908049	236587402	236587490
ENSE00000908050	236587948	236588043
ENSE00000908052	236591993	236592110
ENSE00000908054	236594012	236594114
ENSE00000908055	236595540	236595673
ENSE00000908059	236599483	236599624
ENSE00000908060	236603160	236603376
ENSE00001166811	236595833	236596044
ENSE00001166874	236557195	236557345
ENSE00001211231	236558237	236558529
ENSE00001211234	236558995	236559135
ENSE00001211239	236559714	236559837
ENSE00001211246	236561225	236561271
ENSE00001211323	236585025	236585216
ENSE00001211355	236590847	236590954
ENSE00001211369	236592523	236592633
ENSE00001442096	236603954	236604127
ENSE00001850894	236549005	236550990
ENSE00003479239	236597878	236597979
ENSE00003607969	236596836	236596976
ENSE00003842466	236604422	236604516

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 93.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.3490 / max 130.4438, expressed in 1782 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18230	17.4808	1775
18231	0.8682	438

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	93.92	silver quality
cervix squamous epithelium	UBERON:0006922	93.54	gold quality
secondary oocyte	CL:0000655	93.26	gold quality
gingival epithelium	UBERON:0001949	92.83	gold quality
hair follicle	UBERON:0002073	92.60	gold quality
epithelium of nasopharynx	UBERON:0001951	92.41	gold quality
tendon of biceps brachii	UBERON:0008188	91.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.03	gold quality
squamous epithelium	UBERON:0006914	90.79	gold quality
gingiva	UBERON:0001828	90.78	gold quality
endothelial cell	CL:0000115	90.10	gold quality
epithelial cell of pancreas	CL:0000083	89.21	gold quality
esophagus squamous epithelium	UBERON:0006920	89.05	gold quality
adrenal tissue	UBERON:0018303	89.01	gold quality
tendon	UBERON:0000043	88.93	gold quality
oocyte	CL:0000023	88.68	gold quality
oviduct epithelium	UBERON:0004804	88.54	gold quality
trabecular bone tissue	UBERON:0002483	88.23	gold quality
sperm	CL:0000019	88.12	gold quality
cartilage tissue	UBERON:0002418	87.95	gold quality
calcaneal tendon	UBERON:0003701	87.63	gold quality
buccal mucosa cell	CL:0002336	87.33	gold quality
pericardium	UBERON:0002407	87.30	gold quality
epithelium of esophagus	UBERON:0001976	87.04	gold quality
epithelium of mammary gland	UBERON:0003244	87.00	gold quality
amniotic fluid	UBERON:0000173	86.97	gold quality
medial globus pallidus	UBERON:0002477	86.82	gold quality
mucosa of urinary bladder	UBERON:0001259	86.77	gold quality
germinal epithelium of ovary	UBERON:0001304	86.76	gold quality
male germ cell	CL:0000015	86.63	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting HEATR1, 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-3163	100.00	77.23	8605
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-556-3P	99.74	68.75	1203

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• Glioma-associated antigen HEATR1 induces functional cytotoxic T lymphocytes in patients with glioma. (PMID:25126583)
• These findings reveal an important role for HEATR1 in ribosome biogenesis. (PMID:29143558)
• HEATR1 deficiency promotes pancreatic cancer proliferation and gemcitabine resistance by up-regulating Nrf2 signaling. (PMID:31785531)
• HEATR1 promotes proliferation in gastric cancer in vitro and in vivo. (PMID:32634230)
• HEATR1, a novel interactor of Pontin/Reptin, stabilizes Pontin/Reptin and promotes cell proliferation of oral squamous cell carcinoma. (PMID:33894417)
• Nucleolar HEAT Repeat Containing 1 Up-regulated by the Mechanistic Target of Rapamycin Complex 1 Signaling Promotes Hepatocellular Carcinoma Growth by Dominating Ribosome Biogenesis and Proteome Homeostasis. (PMID:37247644)
• Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth. (PMID:38225354)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	heatr1	ENSDARG00000099742
mus_musculus	Heatr1	ENSMUSG00000050244
rattus_norvegicus	Heatr1	ENSRNOG00000047594
drosophila_melanogaster	l(2)k09022	FBGN0086451
caenorhabditis_elegans		WBGENE00022739

Protein

Protein identifiers

HEAT repeat-containing protein 1 — Q9H583 (reviewed: Q9H583)

Alternative names: Protein BAP28, U3 small nucleolar RNA-associated protein 10 homolog

All UniProt accessions (3): Q9H583, Q5T3Q7, Q6P664

UniProt curated annotations — full annotation on UniProt →

Function. Ribosome biogenesis factor; required for recruitment of Myc to nucleoli. Involved in nucleolar processing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal RNA transcription by RNA polymerase I. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in neuronal-lineage cell proliferation.

Subunit / interactions. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with MYC; the interaction is required for localization of MYC to the nucleolus.

Subcellular location. Nucleus. Nucleolus.

Miscellaneous. The protein described in this entry is essential for the tumorigenic capacity of precancerous glioblastoma stem cells and their proliferation during tumorigenesis. The protein is overexpressed in patient derived glioblastoma tissue compared to control brains. Overexpression is more pronounced in high grade glioblastomas compared to low grade samples, and expression levels inversely correlate with patient survivability.

Similarity. Belongs to the HEATR1/UTP10 family.

RefSeq proteins (1): NP_060542* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR012954	BP28_C_dom	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR022125	U3snoRNP10_N	Domain
IPR040191	UTP10	Family
IPR056473	HEAT_Utp10/HEAT1	Domain

Pfam: PF08146, PF12397, PF23243

UniProt features (25 total): sequence variant 11, modified residue 5, repeat 5, chain 2, initiator methionine 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7MQA	ELECTRON MICROSCOPY	2.7
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H583-F1	78.80	0.14

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 (5): 2, 516, 1190, 1492, 1

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol

MSigDB gene sets: 155 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_MATURATION_OF_SSU_RRNA, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GARY_CD5_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP

GO Biological Process (9): maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462), rRNA metabolic process (GO:0016072), ribosomal small subunit biogenesis (GO:0042274), positive regulation of transcription by RNA polymerase I (GO:0045943), neural precursor cell proliferation (GO:0061351), protein localization to nucleolus (GO:1902570), positive regulation of rRNA processing (GO:2000234), rRNA processing (GO:0006364), ribosome biogenesis (GO:0042254)

GO Molecular Function (3): RNA binding (GO:0003723), snoRNA binding (GO:0030515), protein binding (GO:0005515)

GO Cellular Component (10): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), nucleolus (GO:0005730), mitochondrion (GO:0005739), membrane (GO:0016020), 90S preribosome (GO:0030686), small-subunit processome (GO:0032040), t-UTP complex (GO:0034455), nucleus (GO:0005634), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleolus	3
cellular anatomical structure	3
ribonucleoprotein complex biogenesis	2
ribosome biogenesis	2
nuclear lumen	2
intracellular membrane-bounded organelle	2
preribosome	2
t-UTP complex	2
nuclear protein-containing complex	2
maturation of SSU-rRNA	1
RNA metabolic process	1
regulation of transcription by RNA polymerase I	1
transcription by RNA polymerase I	1
positive regulation of DNA-templated transcription	1
cell population proliferation	1
protein localization to nucleus	1
rRNA processing	1
positive regulation of RNA metabolic process	1
regulation of rRNA processing	1
RNA processing	1
rRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
binding	1
intracellular membraneless organelle	1
cytoplasm	1
protein-containing complex	1

Protein interactions and networks

STRING

2921 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HEATR1	WDR43	Q15061	974
HEATR1	UTP15	Q8TED0	972
HEATR1	UTP4	Q969X6	966
HEATR1	WDR75	Q8IWA0	914
HEATR1	UTP20	O75691	866
HEATR1	PWP2	Q15269	852
HEATR1	UTP18	Q9Y5J1	836
HEATR1	PDCD11	Q14690	814
HEATR1	WDR36	Q8NI36	788
HEATR1	MPHOSPH10	O00566	736
HEATR1	TBL3	Q12788	732
HEATR1	UTP6	Q9NYH9	718
HEATR1	WDR3	Q9UNX4	712
HEATR1	NAT10	Q9H0A0	672
HEATR1	RCL1	Q9Y2P8	671

IntAct

155 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HEATR1		psi-mi:“MI:0915”(physical association)	0.560
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
HEATR1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
EGFR	NDUFA4	psi-mi:“MI:0914”(association)	0.530
NOL11	WDR43	psi-mi:“MI:0914”(association)	0.530
WDR75	WDR43	psi-mi:“MI:0914”(association)	0.530
TGOLN2	DENND11	psi-mi:“MI:0914”(association)	0.530
VSIG1	TNPO2	psi-mi:“MI:0914”(association)	0.530
HEATR1	DUSP14	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
CD40	EXOC5	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
CD244	MTX2	psi-mi:“MI:0914”(association)	0.530
DGCR2	HOXD13	psi-mi:“MI:0914”(association)	0.530
STOM	EI24	psi-mi:“MI:0914”(association)	0.510
	CAND2	psi-mi:“MI:0914”(association)	0.460
HEATR1	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
C18orf21	HEATR1	psi-mi:“MI:0915”(physical association)	0.400
Cep152	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
Bub1	PEX10	psi-mi:“MI:0914”(association)	0.350
SMC6	IFT88	psi-mi:“MI:0914”(association)	0.350
Mgp	TTI1	psi-mi:“MI:0914”(association)	0.350

BioGRID (290): HEATR1 (Two-hybrid), AAGAB (Two-hybrid), HEATR1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS)

ESM2 similar proteins: A0JM49, A2AKG8, B0V0U5, B1AUR6, C5J7W8, E1BGH8, E1C231, E1C2Z0, E7FGT5, E7FH61, E9Q3L2, F6S215, O08662, O60287, O94822, P42356, P57678, P78527, P97313, Q13315, Q13535, Q14146, Q1RLU1, Q2TAW0, Q3TQQ9, Q3URQ0, Q571H0, Q5RDK1, Q5VW36, Q5WNI9, Q5XI94, Q5ZM41, Q62388, Q6A009, Q6DFV1, Q6PQD5, Q6ZRQ5, Q7SY48, Q86XI2, Q8BKX6

Diamond homologs: Q7SY48, Q9GM44, Q9H583, Q9VM75

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HEATR1	“form complex”	“UTP-A complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	280
Likely benign	27
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

5248 predictions. Top by Δscore:

Variant	Effect	Δscore
1:236550986:TTCAT:T	acceptor_gain	1.0000
1:236550988:CAT:C	acceptor_gain	1.0000
1:236550991:C:CC	acceptor_gain	1.0000
1:236551994:ATTAC:A	donor_loss	1.0000
1:236551995:TTA:T	donor_loss	1.0000
1:236551996:TACC:T	donor_loss	1.0000
1:236551997:A:AT	donor_loss	1.0000
1:236552001:T:A	donor_gain	1.0000
1:236552103:CGAAC:C	acceptor_gain	1.0000
1:236552104:GAAC:G	acceptor_gain	1.0000
1:236552106:AC:A	acceptor_gain	1.0000
1:236552106:ACCTG:A	acceptor_loss	1.0000
1:236552107:CC:C	acceptor_gain	1.0000
1:236552107:CCTG:C	acceptor_loss	1.0000
1:236552108:C:CC	acceptor_gain	1.0000
1:236552108:CTG:C	acceptor_loss	1.0000
1:236552117:A:AC	acceptor_gain	1.0000
1:236552117:A:C	acceptor_gain	1.0000
1:236553563:TGTC:T	donor_gain	1.0000
1:236553576:CTAAC:C	donor_loss	1.0000
1:236553579:A:AT	donor_loss	1.0000
1:236553579:A:C	donor_gain	1.0000
1:236553580:CC:C	donor_loss	1.0000
1:236553735:TCCAG:T	acceptor_gain	1.0000
1:236553736:CCAG:C	acceptor_gain	1.0000
1:236553736:CCAGC:C	acceptor_gain	1.0000
1:236553737:CAG:C	acceptor_gain	1.0000
1:236553737:CAGC:C	acceptor_gain	1.0000
1:236553738:AG:A	acceptor_gain	1.0000
1:236553740:C:CC	acceptor_gain	1.0000

AlphaMissense

14121 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:236566772:C:A	R1394S	0.998
1:236566772:C:G	R1394S	0.998
1:236566773:C:G	R1394T	0.998
1:236566785:A:T	V1390D	0.998
1:236569047:A:C	S1342R	0.998
1:236569047:A:T	S1342R	0.998
1:236569049:T:G	S1342R	0.998
1:236569092:A:C	F1327L	0.998
1:236569092:A:T	F1327L	0.998
1:236569094:A:G	F1327L	0.998
1:236603173:A:G	W116R	0.998
1:236603173:A:T	W116R	0.998
1:236566770:C:G	R1395P	0.997
1:236566773:C:A	R1394M	0.997
1:236569015:A:T	V1353D	0.997
1:236569086:A:C	F1329L	0.997
1:236569086:A:T	F1329L	0.997
1:236569088:A:G	F1329L	0.997
1:236571389:C:G	A1304P	0.997
1:236604073:A:G	L8P	0.997
1:236551999:C:G	D2116H	0.996
1:236552014:C:G	A2111P	0.996
1:236566749:A:G	L1402P	0.996
1:236566798:C:G	A1386P	0.996
1:236569082:C:G	G1331R	0.996
1:236569082:C:T	G1331R	0.996
1:236569117:A:T	V1319D	0.996
1:236571364:G:T	A1312D	0.996
1:236571385:A:G	L1305P	0.996
1:236559756:G:C	F1576L	0.995

dbSNP variants (sampled 300 via entrez): RS1000014641 (1:236569603 C>T), RS1000020618 (1:236594360 T>C), RS1000023963 (1:236571054 A>C), RS1000219782 (1:236605757 T>A), RS1000631586 (1:236577575 G>T), RS1000648669 (1:236583157 T>C), RS1000688376 (1:236567089 G>C), RS1000738462 (1:236582951 T>C,G), RS1000831805 (1:236549098 C>T), RS1000855186 (1:236589601 A>G), RS1000898344 (1:236577739 C>T), RS1000929249 (1:236595876 T>C), RS1001042251 (1:236595631 T>C), RS1001077871 (1:236591183 T>C), RS1001113300 (1:236601642 C>T)

Disease associations

OMIM: gene MIM:620390 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003264_952	Post bronchodilator FEV1/FVC ratio	5.000000e-06
GCST006614_140	Total cholesterol levels	9.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0004574	total cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725196 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.51	IC50	3080	nM	MOLIBRESIB
5.45	Kd	3531	nM	CHEMBL5653589
5.45	ED50	3531	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 8 total; 2 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178912: Inhibition of HEATR1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	3.0800	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148500: Binding affinity to human HEATR1 incubated for 45 mins by Kinobead based pull down assay	kd	3.5311	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	decreases expression	2
Estradiol	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression, decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
geldanamycin	increases expression	1
methylmercuric chloride	increases expression	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
sodium arsenate	increases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
torcetrapib	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651542	Binding	Binding affinity to human HEATR1 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.