UTP6

Summary

UTP6 (UTP6 small subunit processome component, HGNC:18279) is a protein-coding gene on chromosome 17q11.2, encoding U3 small nucleolar RNA-associated protein 6 homolog (Q9NYH9). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. It is a selective cancer dependency (DepMap: 80.5% of cell lines).

Predicted to enable snoRNA binding activity. Involved in ribosomal small subunit biogenesis. Located in chromosome and nucleolus. Part of small-subunit processome.

Source: NCBI Gene 55813 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 109 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 80.5% of screened cell lines
• MANE Select transcript: NM_018428

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18279
Approved symbol	UTP6
Name	UTP6 small subunit processome component
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	HCA66
Ensembl gene	ENSG00000108651
Ensembl biotype	protein_coding
OMIM	620948
Entrez	55813

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000261708, ENST00000477128, ENST00000477860, ENST00000484661, ENST00000490218, ENST00000579459, ENST00000579878, ENST00000581012, ENST00000583408, ENST00000899559, ENST00000899560, ENST00000899561, ENST00000899562, ENST00000940126, ENST00000940127, ENST00000940128, ENST00000940129

RefSeq mRNA: 1 — MANE Select: NM_018428 NM_018428

CCDS: CCDS11269

Canonical transcript exons

ENST00000261708 — 19 exons

Exon	Start	End
ENSE00001944288	31860904	31863516
ENSE00002733138	31901536	31901708
ENSE00003461579	31892747	31892794
ENSE00003466643	31880573	31880754
ENSE00003481823	31885980	31886061
ENSE00003489966	31884424	31884505
ENSE00003510173	31878250	31878327
ENSE00003513037	31865366	31865438
ENSE00003536336	31878702	31878781
ENSE00003542290	31868046	31868112
ENSE00003553842	31875234	31875413
ENSE00003569991	31899646	31899730
ENSE00003596453	31889285	31889403
ENSE00003604895	31894970	31895011
ENSE00003610453	31873378	31873487
ENSE00003655060	31887236	31887313
ENSE00003667202	31873673	31873753
ENSE00003668758	31892260	31892323
ENSE00003676930	31894645	31894737

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 97.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.2393 / max 686.9537, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165248	36.0341	1815
208125	0.2051	64

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.32	gold quality
cerebellar hemisphere	UBERON:0002245	95.38	gold quality
cerebellar cortex	UBERON:0002129	95.35	gold quality
ventricular zone	UBERON:0003053	95.17	gold quality
granulocyte	CL:0000094	95.15	gold quality
monocyte	CL:0000576	94.97	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.96	gold quality
tendon	UBERON:0000043	94.88	gold quality
ganglionic eminence	UBERON:0004023	94.80	gold quality
leukocyte	CL:0000738	94.67	gold quality
mononuclear cell	CL:0000842	94.62	gold quality
adenohypophysis	UBERON:0002196	94.62	gold quality
tibial nerve	UBERON:0001323	94.53	gold quality
right testis	UBERON:0004534	94.49	gold quality
right ovary	UBERON:0002118	94.46	gold quality
cortical plate	UBERON:0005343	94.42	gold quality
lower esophagus mucosa	UBERON:0035834	94.39	gold quality
left testis	UBERON:0004533	94.35	gold quality
cerebellum	UBERON:0002037	94.32	gold quality
left ovary	UBERON:0002119	94.32	gold quality
body of uterus	UBERON:0009853	94.25	gold quality
endocervix	UBERON:0000458	93.90	gold quality
cartilage tissue	UBERON:0002418	93.90	gold quality
body of pancreas	UBERON:0001150	93.80	gold quality
right coronary artery	UBERON:0001625	93.80	gold quality
mucosa of transverse colon	UBERON:0004991	93.80	gold quality
spleen	UBERON:0002106	93.78	gold quality
ascending aorta	UBERON:0001496	93.75	gold quality
embryo	UBERON:0000922	93.73	gold quality
thoracic aorta	UBERON:0001515	93.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting UTP6, 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-4282	99.99	75.36	6408
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-595	98.25	67.44	699
HSA-MIR-4327	97.21	67.71	676
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-346	97.01	66.97	662

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 80.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• Results suggest that reduced expression of HCA66, owing to haploinsufficiency of HCA66 gene, could render NF1 microdeleted patients-derived cells less susceptible to apoptosis. (PMID:17380155)
• Stability of the small gamma-tubulin complex requires HCA66, a protein of the centrosome and the nucleolus. (PMID:19299467)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	utp6	ENSDARG00000098433
mus_musculus	Utp6	ENSMUSG00000035575
rattus_norvegicus	Utp6	ENSRNOG00000014209
drosophila_melanogaster	CG7246	FBGN0030081

Protein

Protein identifiers

U3 small nucleolar RNA-associated protein 6 homolog — Q9NYH9 (reviewed: Q9NYH9)

Alternative names: Hepatocellular carcinoma-associated antigen 66, Multiple hat domains protein

All UniProt accessions (3): Q9NYH9, J3KRR8, J3QSA7

UniProt curated annotations — full annotation on UniProt →

Function. 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 nucleolar processing of pre-18S ribosomal RNA.

Subunit / interactions. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.

Subcellular location. Nucleus. Nucleolus.

Similarity. Belongs to the UTP6 family.

RefSeq proteins (1): NP_060898* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003107	HAT	Repeat
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR013949	Utp6	Family
IPR055347	UTP6_N	Domain
IPR056907	UTP6_C	Domain

Pfam: PF08640, PF24892

UniProt features (9 total): repeat 5, sequence variant 3, chain 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-Q9NYH9-F1	82.97	0.15

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: 102 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA, chr17q11, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, REACTOME_METABOLISM_OF_RNA, GOCC_90S_PRERIBOSOME, GOCC_PRERIBOSOME, GOCC_SMALL_SUBUNIT_PROCESSOME, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED

GO Biological Process (4): maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462), ribosomal small subunit biogenesis (GO:0042274), rRNA processing (GO:0006364), RNA processing (GO:0006396)

GO Molecular Function (2): snoRNA binding (GO:0030515), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), small-subunit processome (GO:0032040), Pwp2p-containing subcomplex of 90S preribosome (GO:0034388), nucleus (GO:0005634)

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
ribosome biogenesis	2
nuclear lumen	2
intracellular membraneless organelle	2
nucleolus	2
nuclear protein-containing complex	2
maturation of SSU-rRNA	1
ribonucleoprotein complex biogenesis	1
RNA processing	1
rRNA metabolic process	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA binding	1
binding	1
cellular anatomical structure	1
preribosome	1
t-UTP complex	1
90S preribosome	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2385 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UTP6	TBL3	Q12788	981
UTP6	UTP18	Q9Y5J1	968
UTP6	WDR36	Q8NI36	951
UTP6	PWP2	Q15269	932
UTP6	WDR3	Q9UNX4	910
UTP6	UTP14A	Q9BVJ6	843
UTP6	CRLF3	Q8IUI8	793
UTP6	UTP3	Q9NQZ2	752
UTP6	UTP15	Q8TED0	744
UTP6	UTP4	Q969X6	743
UTP6	LRRC37B	Q96QE4	719
UTP6	HEATR1	Q9H583	718
UTP6	ADAP2	Q9NPF8	708
UTP6	NOL6	Q9H6R4	691
UTP6	WDR46	O15213	689

IntAct

104 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GPX7	GAK	psi-mi:“MI:0914”(association)	0.640
CRIPTO	AIP	psi-mi:“MI:0914”(association)	0.640
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
GNG8	GNB5	psi-mi:“MI:0914”(association)	0.640
UTP6	GBP1	psi-mi:“MI:0914”(association)	0.560
UTP6	APOE	psi-mi:“MI:0915”(physical association)	0.560
COMT	UTP6	psi-mi:“MI:0915”(physical association)	0.560
TGM2	UTP6	psi-mi:“MI:0915”(physical association)	0.560
KLF11	UTP6	psi-mi:“MI:0915”(physical association)	0.560
HTT	UTP6	psi-mi:“MI:0915”(physical association)	0.560
UTP6	GBP1	psi-mi:“MI:0915”(physical association)	0.560
PLA2G10	CHEK1	psi-mi:“MI:0914”(association)	0.530
GPBP1L1	CNOT1	psi-mi:“MI:0914”(association)	0.530
TAF7L	TAF4	psi-mi:“MI:0914”(association)	0.530
IL4R	RHOBTB3	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480

BioGRID (116): UTP6 (Affinity Capture-MS), UTP6 (Affinity Capture-Western), UTP6 (Affinity Capture-MS), UTP6 (Affinity Capture-MS), KXD1 (Two-hybrid), RHOXF2 (Two-hybrid), UTP6 (Two-hybrid), UTP6 (Affinity Capture-MS), UTP6 (Affinity Capture-MS), UTP6 (Affinity Capture-MS), UTP6 (Affinity Capture-MS), UTP6 (Affinity Capture-MS), UTP6 (Affinity Capture-MS), UTP6 (Affinity Capture-MS), UTP6 (Affinity Capture-MS)

ESM2 similar proteins: A1A5S1, A1Z9G2, B3DJT0, B3MIF1, O01422, O74970, O94906, P0CO10, P0CO11, P17886, P25991, P63154, P63155, P87312, Q12309, Q12381, Q15020, Q2KJJ0, Q4KLU2, Q4PB37, Q4WT84, Q4WVF4, Q527H0, Q52DF3, Q54XP4, Q54Z08, Q5B3U7, Q5BDX1, Q5BH69, Q5K654, Q5RCC2, Q5REG1, Q6BSP7, Q6C186, Q6CAR6, Q750X3, Q7SAK5, Q7SGD2, Q7SI58, Q86UA1

Diamond homologs: O60188, Q02354, Q54WN5, Q8VCY6, Q9NYH9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UTP6	“form complex”	“UTP-B complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	76
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
564426	GRCh37/hg19 17q11.2(chr17:29003358-30412788)x1	Pathogenic

SpliceAI

2670 predictions. Top by Δscore:

Variant	Effect	Δscore
17:31863517:C:CC	acceptor_gain	1.0000
17:31863518:T:C	acceptor_gain	1.0000
17:31863520:T:C	acceptor_gain	1.0000
17:31863520:T:TC	acceptor_gain	1.0000
17:31865360:ACTT:A	donor_loss	1.0000
17:31865361:CTT:C	donor_loss	1.0000
17:31865362:TTA:T	donor_loss	1.0000
17:31865363:TAC:T	donor_loss	1.0000
17:31865364:A:T	donor_loss	1.0000
17:31865436:TTC:T	acceptor_gain	1.0000
17:31865436:TTCC:T	acceptor_loss	1.0000
17:31865437:TCCTG:T	acceptor_loss	1.0000
17:31865438:CCTG:C	acceptor_loss	1.0000
17:31865439:CTGAC:C	acceptor_loss	1.0000
17:31865440:T:A	acceptor_loss	1.0000
17:31868044:A:AC	donor_gain	1.0000
17:31868045:C:CT	donor_gain	1.0000
17:31868045:CTTG:C	donor_gain	1.0000
17:31868109:TAAA:T	acceptor_gain	1.0000
17:31868111:AA:A	acceptor_gain	1.0000
17:31868113:C:CC	acceptor_gain	1.0000
17:31875410:CACT:C	acceptor_gain	1.0000
17:31875412:CT:C	acceptor_gain	1.0000
17:31878244:TCTTA:T	donor_loss	1.0000
17:31878245:CTTAC:C	donor_loss	1.0000
17:31878246:TTAC:T	donor_loss	1.0000
17:31878247:TA:T	donor_loss	1.0000
17:31878248:AC:A	donor_loss	1.0000
17:31878249:CC:C	donor_loss	1.0000
17:31878249:CCAA:C	donor_gain	1.0000

AlphaMissense

3955 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:31887297:A:G	L187P	0.994
17:31863511:A:G	W548R	0.992
17:31863511:A:T	W548R	0.992
17:31863436:C:G	A573P	0.988
17:31889385:G:T	A148D	0.987
17:31889398:A:G	W144R	0.984
17:31889398:A:T	W144R	0.984
17:31889386:C:G	A148P	0.983
17:31901572:A:G	L19P	0.983
17:31863435:G:T	A573E	0.982
17:31863438:C:G	R572P	0.979
17:31889326:C:G	A168P	0.976
17:31889325:G:T	A168E	0.974
17:31889343:C:G	R162T	0.972
17:31894976:T:A	R71S	0.972
17:31894976:T:G	R71S	0.972
17:31894989:A:G	L67P	0.971
17:31889342:C:A	R162S	0.970
17:31889342:C:G	R162S	0.970
17:31889346:G:T	A161E	0.970
17:31894973:T:A	R72S	0.970
17:31894973:T:G	R72S	0.970
17:31863509:C:A	W548C	0.969
17:31863509:C:G	W548C	0.969
17:31865382:A:C	F540L	0.966
17:31865382:A:T	F540L	0.966
17:31865384:A:G	F540L	0.966
17:31889343:C:A	R162M	0.966
17:31894998:A:G	L64P	0.966
17:31889389:C:G	A147P	0.965

dbSNP variants (sampled 300 via entrez): RS1000043203 (17:31861816 T>A), RS1000077478 (17:31862060 C>T), RS1000106250 (17:31882862 G>A,T), RS1000138850 (17:31882123 T>A,C), RS1000177389 (17:31885297 A>G), RS1000195681 (17:31891043 T>C), RS1000249547 (17:31867333 C>A), RS1000355917 (17:31879823 C>T), RS1000407547 (17:31885867 C>T), RS1000436696 (17:31866458 G>A), RS1000464406 (17:31885926 T>C,G), RS1000470966 (17:31861181 G>A), RS1000536222 (17:31902519 C>A,G), RS1000603025 (17:31860975 A>G), RS1000649338 (17:31890808 G>A)

Disease associations

OMIM: gene MIM:620948 | 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
GCST008949_2	High chromosomal aberration frequency (chromosome type) in genotoxic compound exposure	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009861	chromosome-type aberration frequency

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, decreases expression, increases expression, affects methylation, affects cotreatment	3
Aflatoxin B1	decreases methylation, increases expression, affects cotreatment, decreases expression	3
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
TL8-506	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	decreases expression	1
Nickel	decreases expression	1
Phenolsulfonphthalein	affects cotreatment, increases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Poly I-C	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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