HEATR6

Summary

HEATR6 (HEAT repeat containing 6, HGNC:24076) is a protein-coding gene on chromosome 17q23.1, encoding HEAT repeat-containing protein 6 (Q6AI08). Amplification-dependent oncogene.

Enables RNA binding activity.

Source: NCBI Gene 63897 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 199 total
• Druggable target: yes
• MANE Select transcript: NM_022070

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24076
Approved symbol	HEATR6
Name	HEAT repeat containing 6
Location	17q23.1
Locus type	gene with protein product
Status	Approved
Aliases	ABC1, FLJ22087
Ensembl gene	ENSG00000068097
Ensembl biotype	protein_coding
Entrez	63897

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000184956, ENST00000585712, ENST00000585976, ENST00000587003, ENST00000587314, ENST00000590587, ENST00000591074, ENST00000591683, ENST00000592664, ENST00000593097, ENST00000593228, ENST00000863467, ENST00000863468, ENST00000863469, ENST00000863470, ENST00000932001, ENST00000932002, ENST00000932003

RefSeq mRNA: 1 — MANE Select: NM_022070 NM_022070

CCDS: CCDS11623

Canonical transcript exons

ENST00000184956 — 20 exons

Exon	Start	End
ENSE00001112993	60067434	60067732
ENSE00001112996	60066209	60066386
ENSE00001113010	60069711	60069848
ENSE00001242323	60073746	60073886
ENSE00001431440	60041008	60044134
ENSE00003475523	60070706	60070807
ENSE00003495922	60055515	60055601
ENSE00003502875	60048264	60048388
ENSE00003504306	60046025	60046229
ENSE00003506476	60059422	60059521
ENSE00003508020	60076130	60076237
ENSE00003536886	60072215	60072329
ENSE00003547909	60049580	60049702
ENSE00003556097	60073164	60073279
ENSE00003597443	60059890	60060096
ENSE00003610226	60050843	60050977
ENSE00003633760	60078696	60078921
ENSE00003645079	60056115	60056237
ENSE00003649712	60057048	60057403
ENSE00003664229	60047309	60047405

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 86.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8265 / max 186.0438, expressed in 1794 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167358	18.8265	1794

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	86.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.54	gold quality
ganglionic eminence	UBERON:0004023	85.49	gold quality
stromal cell of endometrium	CL:0002255	85.37	gold quality
endothelial cell	CL:0000115	85.28	gold quality
cortical plate	UBERON:0005343	83.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.59	gold quality
cerebellar hemisphere	UBERON:0002245	83.22	gold quality
cerebellar cortex	UBERON:0002129	83.10	gold quality
apex of heart	UBERON:0002098	82.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.75	gold quality
adrenal tissue	UBERON:0018303	82.71	gold quality
sural nerve	UBERON:0015488	82.61	gold quality
right adrenal gland cortex	UBERON:0035827	82.60	gold quality
right adrenal gland	UBERON:0001233	82.59	gold quality
cerebellum	UBERON:0002037	82.41	gold quality
granulocyte	CL:0000094	82.40	gold quality
left ovary	UBERON:0002119	82.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.29	gold quality
corpus callosum	UBERON:0002336	82.08	gold quality
right ovary	UBERON:0002118	81.98	gold quality
body of uterus	UBERON:0009853	81.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.91	gold quality
left adrenal gland cortex	UBERON:0035825	81.80	gold quality
left adrenal gland	UBERON:0001234	81.65	gold quality
calcaneal tendon	UBERON:0003701	81.53	gold quality
adrenal cortex	UBERON:0001235	81.52	gold quality
pituitary gland	UBERON:0000007	81.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.27	gold quality
adrenal gland	UBERON:0002369	81.17	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	6.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting HEATR6, 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-4666A-3P	99.96	71.71	3434
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-4687-5P	99.14	66.26	488
HSA-MIR-647	97.73	67.79	927
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-1233-3P	96.81	65.44	573
HSA-MIR-6735-3P	96.10	63.81	600

Literature-anchored findings (GeneRIF, showing 1)

• [The relationship between the expression of amplified in breast cancer 1androgen receptor and tamoxifen resistance in breast cancer]. (PMID:37246005)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	heatr6	ENSDARG00000073686
mus_musculus	Heatr6	ENSMUSG00000000976
rattus_norvegicus	Heatr6	ENSRNOG00000002542
drosophila_melanogaster	CG16989	FBGN0025621

Protein

Protein identifiers

HEAT repeat-containing protein 6 — Q6AI08 (reviewed: Q6AI08)

Alternative names: Amplified in breast cancer protein 1

All UniProt accessions (9): Q6AI08, K7EIX2, K7EK31, K7EKB1, K7EKF5, K7EKW7, K7ELA5, K7ELR8, K7ESP5

UniProt curated annotations — full annotation on UniProt →

Function. Amplification-dependent oncogene.

Tissue specificity. Amplified in breast cancer cell lines MCF-7 and BT-474.

Miscellaneous. 17q23 region is one of the most commonly amplified regions in breast cancer and therefore may harbor genes important for breast cancer development and progression.

RefSeq proteins (1): NP_071353* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR025283	DUF4042	Domain
IPR052107	HEAT6	Family

Pfam: PF13251

UniProt features (35 total): sequence conflict 16, modified residue 6, repeat 4, compositionally biased region 3, region of interest 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6AI08-F1	80.84	0.61

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 (6): 336, 337, 399, 402, 618, 643

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, PATIL_LIVER_CANCER, MODULE_331, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, WANG_LMO4_TARGETS_DN, DOANE_RESPONSE_TO_ANDROGEN_DN, MODULE_301, KIM_GASTRIC_CANCER_CHEMOSENSITIVITY, GAUSSMANN_MLL_AF4_FUSION_TARGETS_B_UP, MODULE_397, MODULE_188, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, PARENT_MTOR_SIGNALING_UP, CASORELLI_ACUTE_PROMYELOCYTIC_LEUKEMIA_DN, chr17q23

GO Biological Process (0):

GO Molecular Function (1): RNA binding (GO:0003723)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	1

Protein interactions and networks

STRING

504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HEATR6	NCOA3	Q9Y6Q9	934
HEATR6	ESR1	P03372	798
HEATR6	ERBB2	P04626	605
HEATR6	NCOA1	Q15788	580
HEATR6	AR	P10275	577
HEATR6	E2F1	Q01094	576
HEATR6	NCOA2	Q15596	571
HEATR6	DLL3	Q9NYJ7	561
HEATR6	NCOA6	Q14686	559
HEATR6	ETV4	P43268	516
HEATR6	KAT2B	Q92831	515
HEATR6	CCND1	P24385	494
HEATR6	PDXP	Q96GD0	490
HEATR6	CHCT1	Q86WR6	483
HEATR6	CREBBP	Q92793	479

IntAct

103 interactions, top by confidence:

A	B	Type	Score
HRAS	RAF1	psi-mi:“MI:0914”(association)	0.980
PRKAB1	PRKAB2	psi-mi:“MI:0914”(association)	0.740
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
NME3	NME4	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
SPACA1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
PLA2G10	CHEK1	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
STK16	UNC119B	psi-mi:“MI:0914”(association)	0.530
HAX1	CHEK1	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
PDCD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
BSG	METTL15	psi-mi:“MI:0914”(association)	0.350
ICAM1	RTL8C	psi-mi:“MI:0914”(association)	0.350
GLMP	RTL8C	psi-mi:“MI:0914”(association)	0.350
NTRK3	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SNX21	POLR1G	psi-mi:“MI:0914”(association)	0.350
HLA-B		psi-mi:“MI:0914”(association)	0.350
SDC2	METTL8	psi-mi:“MI:0914”(association)	0.350
CD79B	GOLIM4	psi-mi:“MI:0914”(association)	0.350
IQCF1	TBC1D4	psi-mi:“MI:0914”(association)	0.350
CD244	CAND2	psi-mi:“MI:0914”(association)	0.350
PA	DDX39A	psi-mi:“MI:0914”(association)	0.350
M	TM9SF1	psi-mi:“MI:0914”(association)	0.350
LIMK1	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (127): HEATR6 (Affinity Capture-MS), HEATR6 (Affinity Capture-MS), HEATR6 (Affinity Capture-MS), HEATR6 (Affinity Capture-MS), HEATR6 (Affinity Capture-MS), HEATR6 (Affinity Capture-MS), GAS8 (Co-fractionation), RBM15 (Co-fractionation), RPP30 (Co-fractionation), HEATR6 (Affinity Capture-MS), HEATR6 (Synthetic Growth Defect), HEATR6 (Affinity Capture-MS), HEATR6 (Affinity Capture-MS), HEATR6 (Affinity Capture-MS), HEATR6 (Affinity Capture-MS)

ESM2 similar proteins: A0JP94, A1A5F2, A1EC95, A2BID5, A9JRI0, E7FAW3, E7FBU4, E9PVA8, F4HRS2, F4IP13, K8ERU3, O35095, O43299, P42695, P49815, P49816, Q08CY4, Q0DJS1, Q28205, Q2KJ97, Q3U829, Q3UHQ6, Q5JWR5, Q5PRF0, Q5R5R2, Q5SPP5, Q5ZIG0, Q61037, Q640K1, Q642P2, Q68F70, Q6AI08, Q6GN08, Q6GPP1, Q6P1G0, Q6ZNJ1, Q6ZQA0, Q6ZQK0, Q7T006, Q7ZY56

Diamond homologs: A1EC95, A9JRI0, Q5R5R2, Q6AI08, Q6P1G0, Q7ZY56

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 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
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	9	9.1×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
adaptive immune response	10	6.9×	2e-03
cell surface receptor signaling pathway	10	5.2×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	175
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3203 predictions. Top by Δscore:

Variant	Effect	Δscore
17:60044135:C:CC	acceptor_gain	1.0000
17:60044135:CTA:C	acceptor_loss	1.0000
17:60044136:T:G	acceptor_loss	1.0000
17:60047416:C:T	acceptor_gain	1.0000
17:60048152:A:AC	donor_gain	1.0000
17:60048153:C:CC	donor_gain	1.0000
17:60048262:A:AC	donor_gain	1.0000
17:60048263:C:CC	donor_gain	1.0000
17:60048263:CATG:C	donor_gain	1.0000
17:60048385:CATC:C	acceptor_gain	1.0000
17:60048389:C:CC	acceptor_gain	1.0000
17:60049572:A:AC	donor_gain	1.0000
17:60049573:C:CC	donor_gain	1.0000
17:60049606:AGACT:A	donor_gain	1.0000
17:60049611:C:CA	donor_gain	1.0000
17:60050842:CCGG:C	donor_gain	1.0000
17:60056110:ATTAC:A	donor_loss	1.0000
17:60056111:TTAC:T	donor_loss	1.0000
17:60056112:TAC:T	donor_loss	1.0000
17:60056113:A:AC	donor_gain	1.0000
17:60056114:C:CA	donor_loss	1.0000
17:60056114:C:CC	donor_gain	1.0000
17:60056233:AATAC:A	acceptor_gain	1.0000
17:60056234:ATAC:A	acceptor_gain	1.0000
17:60056235:TAC:T	acceptor_gain	1.0000
17:60056236:AC:A	acceptor_gain	1.0000
17:60056237:CC:C	acceptor_gain	1.0000
17:60056237:CCTG:C	acceptor_loss	1.0000
17:60056238:C:CC	acceptor_gain	1.0000
17:60059518:GGCA:G	acceptor_gain	1.0000

AlphaMissense

7655 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:60046079:A:G	W974R	0.999
17:60046079:A:T	W974R	0.999
17:60044064:T:A	K1015N	0.998
17:60044064:T:G	K1015N	0.998
17:60046077:C:A	W974C	0.998
17:60046077:C:G	W974C	0.998
17:60048288:A:G	L883P	0.998
17:60048304:A:G	W878R	0.998
17:60048304:A:T	W878R	0.998
17:60050965:A:G	W768R	0.998
17:60050965:A:T	W768R	0.998
17:60060092:C:G	R474P	0.998
17:60044065:T:A	K1015I	0.997
17:60066367:G:T	R420S	0.997
17:60046201:C:T	G933E	0.996
17:60048297:A:G	L880P	0.996
17:60048364:C:G	A858P	0.996
17:60049612:C:G	G839R	0.996
17:60049612:C:T	G839R	0.996
17:60057373:A:G	L585P	0.996
17:60057381:A:C	S582R	0.996
17:60057381:A:T	S582R	0.996
17:60057383:T:G	S582R	0.996
17:60059945:A:G	L523P	0.996
17:60060093:G:T	R474S	0.996
17:60066366:C:G	R420P	0.996
17:60044066:T:C	K1015E	0.995
17:60046202:C:G	G933R	0.995
17:60046202:C:T	G933R	0.995
17:60049611:C:T	G839E	0.995

dbSNP variants (sampled 300 via entrez): RS1000020598 (17:60052732 G>A), RS1000061511 (17:60059213 A>G), RS1000133281 (17:60060467 C>T), RS1000218984 (17:60047384 G>A), RS1000233488 (17:60060285 T>A,C), RS1000261105 (17:60051679 A>C), RS1000290088 (17:60067155 A>G), RS1000377197 (17:60074990 C>T), RS1000701222 (17:60046154 A>C), RS1000829943 (17:60061864 A>G), RS1000889389 (17:60068949 A>G), RS1000939897 (17:60046574 C>G,T), RS1000959209 (17:60074312 G>A,C), RS1001288867 (17:60051095 G>A,C), RS1001538335 (17:60062291 T>C)

Disease associations

OMIM: gene `` | 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
GCST012490_177	Femur bone mineral density x serum urate levels interaction	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067147 (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
7.04	Kd	90.2	nM	CHEMBL5653589
7.04	ED50	90.2	nM	CHEMBL5653589

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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148501: Binding affinity to human HEATR6 incubated for 45 mins by Kinobead based pull down assay	kd	0.0902	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression, increases abundance, affects cotreatment	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
abrine	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Acetaminophen	increases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Potassium Dichromate	increases expression	1
Quercetin	increases phosphorylation	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Urethane	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases 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
CHEMBL5651543	Binding	Binding affinity to human HEATR6 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.