ZNHIT6

Summary

ZNHIT6 (zinc finger HIT-type containing 6, HGNC:26089) is a protein-coding gene on chromosome 1p22.3, encoding Box C/D snoRNA protein 1 (Q9NWK9). Required for box C/D snoRNAs accumulation involved in snoRNA processing, snoRNA transport to the nucleolus and ribosome biogenesis. It is a selective cancer dependency (DepMap: 69.1% of cell lines).

Enables ATPase binding activity; TFIID-class transcription factor complex binding activity; and identical protein binding activity. Involved in box C/D snoRNP assembly; protein complex oligomerization; and snoRNA localization. Located in extracellular exosome. Part of pre-snoRNP complex.

Source: NCBI Gene 54680 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 84 total
• Cancer dependency (DepMap): dependent in 69.1% of screened cell lines
• MANE Select transcript: NM_017953

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26089
Approved symbol	ZNHIT6
Name	zinc finger HIT-type containing 6
Location	1p22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20729, NY-BR-75, BCD1
Ensembl gene	ENSG00000117174
Ensembl biotype	protein_coding
OMIM	620473
Entrez	54680

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000370574, ENST00000431532, ENST00000879064

RefSeq mRNA: 2 — MANE Select: NM_017953 NM_001170670, NM_017953

CCDS: CCDS53338, CCDS707

Canonical transcript exons

ENST00000370574 — 10 exons

Exon	Start	End
ENSE00000775849	85677236	85677313
ENSE00000775851	85678701	85678781
ENSE00000775852	85680836	85680904
ENSE00001013034	85657847	85657971
ENSE00001067294	85706442	85706507
ENSE00001067295	85706078	85706163
ENSE00001067296	85706249	85706355
ENSE00001067297	85702157	85702260
ENSE00001453062	85707629	85708433
ENSE00001829179	85649417	85654098

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 91.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7500 / max 846.8632, expressed in 1792 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13081	23.0389	1784
13079	1.8729	832
13080	0.8382	495

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	91.16	gold quality
cranial nerve II	UBERON:0000941	90.23	gold quality
esophagus squamous epithelium	UBERON:0006920	89.39	gold quality
buccal mucosa cell	CL:0002336	88.28	gold quality
palpebral conjunctiva	UBERON:0001812	88.11	gold quality
epithelium of esophagus	UBERON:0001976	87.83	gold quality
urethra	UBERON:0000057	87.09	gold quality
inferior vagus X ganglion	UBERON:0005363	87.06	gold quality
skin of hip	UBERON:0001554	86.98	gold quality
medial globus pallidus	UBERON:0002477	86.51	gold quality
medulla oblongata	UBERON:0001896	86.14	gold quality
globus pallidus	UBERON:0001875	85.93	gold quality
upper leg skin	UBERON:0004262	85.74	gold quality
subthalamic nucleus	UBERON:0001906	85.73	gold quality
calcaneal tendon	UBERON:0003701	85.66	gold quality
superior vestibular nucleus	UBERON:0007227	85.56	gold quality
pons	UBERON:0000988	84.62	gold quality
pericardium	UBERON:0002407	84.62	gold quality
cauda epididymis	UBERON:0004360	84.61	gold quality
superficial temporal artery	UBERON:0001614	84.27	gold quality
substantia nigra pars reticulata	UBERON:0001966	84.11	gold quality
synovial joint	UBERON:0002217	84.05	gold quality
epithelium of nasopharynx	UBERON:0001951	83.89	gold quality
cartilage tissue	UBERON:0002418	83.84	gold quality
lateral globus pallidus	UBERON:0002476	83.68	gold quality
saphenous vein	UBERON:0007318	83.62	gold quality
blood vessel layer	UBERON:0004797	83.60	gold quality
epithelium of mammary gland	UBERON:0003244	83.54	gold quality
mammary duct	UBERON:0001765	83.53	gold quality
nasal cavity mucosa	UBERON:0001826	83.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

173 targeting ZNHIT6, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-548AE-3P	99.93	72.66	4867

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 69.1% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	znhit6	ENSDARG00000095817
mus_musculus	Znhit6	ENSMUSG00000074182
rattus_norvegicus	Znhit6	ENSRNOG00000030049
drosophila_melanogaster	CG1463	FBGN0030406
caenorhabditis_elegans		WBGENE00006489

Protein

Protein identifiers

Box C/D snoRNA protein 1 — Q9NWK9 (reviewed: Q9NWK9)

Alternative names: Serologically defined breast cancer antigen NY-BR-75, Zinc finger HIT domain-containing protein 6

All UniProt accessions (1): Q9NWK9

UniProt curated annotations — full annotation on UniProt →

Function. Required for box C/D snoRNAs accumulation involved in snoRNA processing, snoRNA transport to the nucleolus and ribosome biogenesis.

Subunit / interactions. Interacts with FBL, SNU13, NOP58, NUFIP1, RUVBL1, RUVBL2 and TAF9. Interacts (via HIT-type zinc finger) with the RUVBL1/RUVBL2 complex in the presence of ADP.

Similarity. Belongs to the BCD1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NWK9-1	1	yes
Q9NWK9-2	2

RefSeq proteins (2): NP_001164141, NP_060423* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007529	Znf_HIT	Domain
IPR051639	BCD1	Family
IPR057721	BCD1_alpha/beta	Domain

Pfam: PF04438, PF25790

UniProt features (28 total): cross-link 11, binding site 8, sequence variant 2, chain 1, zinc finger region 1, modified residue 1, region of interest 1, splice variant 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWK9-F1	60.96	0.17

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): 248; 254; 220; 223; 232; 235; 240; 244

Post-translational modifications (12): 25, 79, 108, 118, 138, 143, 153, 162, 173, 183, 200, 459

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_MATURATION_OF_LSU_RRNA, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, chr1p22, GOBP_RNA_LOCALIZATION, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_RIBOSOMAL_LARGE_SUBUNIT_BIOGENESIS, USF2_Q6, GOCC_RIBONUCLEOPROTEIN_COMPLEX, GOMF_ATPASE_BINDING, GOMF_TRANSCRIPTION_FACTOR_BINDING, GOMF_BASAL_TRANSCRIPTION_MACHINERY_BINDING, PUIFFE_INVASION_INHIBITED_BY_ASCITES_DN, GOBP_MATURATION_OF_LSU_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GOBP_SMALL_NUCLEOLAR_RIBONUCLEOPROTEIN_COMPLEX_ASSEMBLY

GO Biological Process (5): maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000463), box C/D snoRNP assembly (GO:0000492), snoRNA localization (GO:0048254), protein complex oligomerization (GO:0051259), ribosome biogenesis (GO:0042254)

GO Molecular Function (7): TFIID-class transcription factor complex binding (GO:0001094), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), identical protein binding (GO:0042802), ATPase binding (GO:0051117), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), extracellular exosome (GO:0070062), pre-snoRNP complex (GO:0070761)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
maturation of LSU-rRNA	1
small nucleolar ribonucleoprotein complex assembly	1
RNA localization	1
protein-containing complex assembly	1
ribonucleoprotein complex biogenesis	1
RNA polymerase II general transcription initiation factor binding	1
transition metal ion binding	1
enzyme binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

1354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNHIT6	ZNHIT3	Q15649	880
ZNHIT6	NUFIP1	Q9UHK0	847
ZNHIT6	ZNHIT1	O43257	694
ZNHIT6	PIH1D1	Q9NWS0	673
ZNHIT6	ZNHIT2	Q9UHR6	660
ZNHIT6	RUVBL2	Q9Y230	642
ZNHIT6	RPAP3	Q9H6T3	626
ZNHIT6	RUVBL1	P82276	601
ZNHIT6	INO80B	Q9C086	598
ZNHIT6	NOP58	Q9Y2X3	570
ZNHIT6	ZC3H7A	Q8IWR0	566
ZNHIT6	MVB12A	Q96EY5	547
ZNHIT6	TTI1	O43156	519
ZNHIT6	SNU13	P55769	507
ZNHIT6	RRP36	Q96EU6	489

IntAct

73 interactions, top by confidence:

A	B	Type	Score
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
NUFIP1	ZNHIT3	psi-mi:“MI:0914”(association)	0.840
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
TUBB	PLD2	psi-mi:“MI:0914”(association)	0.640
NOP58	NOP56	psi-mi:“MI:0914”(association)	0.640
NUFIP1	ZNHIT6	psi-mi:“MI:0915”(physical association)	0.560
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
TGM5	UBB	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
Snu13		psi-mi:“MI:0915”(physical association)	0.400
ZNHIT6	ZNHIT6	psi-mi:“MI:0915”(physical association)	0.400
Ruvbl2	ZNHIT6	psi-mi:“MI:0915”(physical association)	0.400
SMAD2	ZNHIT6	psi-mi:“MI:0915”(physical association)	0.370
Ruvbl1	AAR2	psi-mi:“MI:0914”(association)	0.350
TENT5A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CDC16	KRBA1	psi-mi:“MI:0914”(association)	0.350
ASB3	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
F9	DDX11L8	psi-mi:“MI:0914”(association)	0.350
IL17RA	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SKAP1	MYO9A	psi-mi:“MI:0914”(association)	0.350
PCDH20		psi-mi:“MI:0914”(association)	0.350
CARD8	HDAC3	psi-mi:“MI:0914”(association)	0.350
PROZ	ARVCF	psi-mi:“MI:0914”(association)	0.350

BioGRID (115): ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS), ZNHIT6 (Affinity Capture-MS)

ESM2 similar proteins: A6H5X4, B2RX14, D0QMC3, D3ZF42, F6QRE9, O14862, O35368, P0C6Y7, P0DOV1, P0DOV2, P23497, P41218, Q13342, Q15361, Q16666, Q17RS7, Q3KRF1, Q504N7, Q5H9K5, Q5I0E2, Q5RD14, Q5RF97, Q5T4T6, Q5VYS8, Q5W0A0, Q62187, Q66JT0, Q6K0P9, Q6NYJ3, Q6ZMT9, Q7RTT4, Q80VH0, Q86X53, Q8BUH8, Q8BV49, Q8BVK9, Q8C0V1, Q8CGE8, Q8NDB2, Q8SPH9

Diamond homologs: O36031, P46973, Q2KIH1, Q5RF97, Q6UIM1, Q9NWK9, Q3UFB2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1809 predictions. Top by Δscore:

Variant	Effect	Δscore
1:85654094:CTTCA:C	acceptor_gain	1.0000
1:85654097:CA:C	acceptor_gain	1.0000
1:85654099:C:CC	acceptor_gain	1.0000
1:85657979:A:AC	acceptor_gain	1.0000
1:85657979:A:C	acceptor_gain	1.0000
1:85677231:TTTA:T	donor_loss	1.0000
1:85677232:TTACC:T	donor_loss	1.0000
1:85677233:TA:T	donor_loss	1.0000
1:85677239:A:AC	donor_gain	1.0000
1:85677240:C:CC	donor_gain	1.0000
1:85677313:CCT:C	acceptor_loss	1.0000
1:85677315:T:C	acceptor_loss	1.0000
1:85678695:GCATA:G	donor_loss	1.0000
1:85678696:CATAC:C	donor_loss	1.0000
1:85678697:ATAC:A	donor_loss	1.0000
1:85678698:TACCT:T	donor_loss	1.0000
1:85678699:A:C	donor_loss	1.0000
1:85678700:C:CA	donor_loss	1.0000
1:85678778:TACT:T	acceptor_gain	1.0000
1:85678780:CT:C	acceptor_gain	1.0000
1:85678780:CTC:C	acceptor_loss	1.0000
1:85678781:TCT:T	acceptor_loss	1.0000
1:85678782:C:CC	acceptor_gain	1.0000
1:85678783:T:C	acceptor_gain	1.0000
1:85678783:T:TC	acceptor_gain	1.0000
1:85678784:T:C	acceptor_gain	1.0000
1:85678784:T:TC	acceptor_gain	1.0000
1:85678787:C:CT	acceptor_gain	1.0000
1:85678788:A:T	acceptor_gain	1.0000
1:85678790:C:CT	acceptor_gain	1.0000

AlphaMissense

3138 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:85680888:A:G	W346R	0.999
1:85680888:A:T	W346R	0.999
1:85680869:A:G	F352S	0.998
1:85680875:A:G	L350P	0.998
1:85702238:G:T	A313D	0.998
1:85706151:A:G	L281S	0.998
1:85706157:C:G	R279P	0.998
1:85706257:A:G	L274P	0.998
1:85706470:A:G	C232R	0.998
1:85706476:A:G	Y230H	0.998
1:85680886:C:A	W346C	0.997
1:85680886:C:G	W346C	0.997
1:85680887:C:G	W346S	0.997
1:85657903:G:T	P439Q	0.996
1:85657909:T:A	E437V	0.996
1:85678749:A:G	L374P	0.996
1:85706163:T:A	D277V	0.996
1:85706163:T:G	D277A	0.996
1:85706249:C:G	D277H	0.996
1:85706311:C:T	G256E	0.996
1:85706331:T:A	K249N	0.996
1:85706331:T:G	K249N	0.996
1:85706461:A:G	C235R	0.996
1:85706506:A:G	C220R	0.996
1:85680868:A:C	F352L	0.995
1:85680868:A:T	F352L	0.995
1:85680870:A:G	F352L	0.995
1:85702177:A:C	N333K	0.995
1:85702177:A:T	N333K	0.995
1:85706318:A:G	C254R	0.995

dbSNP variants (sampled 300 via entrez): RS1000154701 (1:85680076 T>G), RS1000231408 (1:85673908 C>T), RS1000242561 (1:85680065 G>A), RS1000398591 (1:85666003 T>G), RS1000432465 (1:85709796 T>C), RS1000463459 (1:85709402 A>G), RS1000549959 (1:85699138 CTT>C), RS1000568629 (1:85675626 C>A,T), RS1000651096 (1:85648922 G>C), RS1000653295 (1:85692341 T>C), RS1000698620 (1:85654760 G>A,C), RS1000735417 (1:85686115 C>A), RS1000809657 (1:85668236 A>C), RS1000905427 (1:85667833 C>A), RS1000987011 (1:85698859 A>G)

Disease associations

OMIM: gene MIM:620473 | 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
GCST002829_12	Urate levels in overweight individuals	9.000000e-06
GCST90020025_250	Waist-to-hip ratio adjusted for BMI	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	3
Cisplatin	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression, increases methylation	2
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
coumarin	increases phosphorylation	1
perfluorooctane sulfonic acid	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	increases phosphorylation	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	increases expression	1
Indomethacin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2LY	Abcam HeLa ZNHIT6 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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