ZNF217

Summary

ZNF217 (zinc finger protein 217, HGNC:13009) is a protein-coding gene on chromosome 20q13.2, encoding Zinc finger protein 217 (O75362). Binds to the promoters of target genes and functions as repressor. It is a selective cancer dependency (DepMap: 40.0% of cell lines).

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in mitochondrion and nuclear speck. Part of histone deacetylase complex.

Source: NCBI Gene 7764 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 156 total
• Cancer dependency (DepMap): dependent in 40.0% of screened cell lines
• MANE Select transcript: NM_006526

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13009
Approved symbol	ZNF217
Name	zinc finger protein 217
Location	20q13.2
Locus type	gene with protein product
Status	Approved
Aliases	ZABC1
Ensembl gene	ENSG00000171940
Ensembl biotype	protein_coding
OMIM	602967
Entrez	7764

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000302342, ENST00000371471, ENST00000431687, ENST00000437222, ENST00000540425

RefSeq mRNA: 2 — MANE Select: NM_006526 NM_001385034, NM_006526

CCDS: CCDS13443

Canonical transcript exons

ENST00000371471 — 6 exons

Exon	Start	End
ENSE00001143007	53571721	53571853
ENSE00001455296	53567071	53569264
ENSE00001523402	53593756	53593839
ENSE00001722637	53578334	53578450
ENSE00001742197	53575727	53577280
ENSE00002726625	53581461	53583168

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 99.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.0484 / max 126.0159, expressed in 1446 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188006	1.9374	829
187997	1.2649	599
188007	0.8562	207
188005	0.7982	414
187996	0.5590	271
188015	0.5314	234
188012	0.3549	67
187998	0.2751	124
188013	0.2008	66
188014	0.1191	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	99.19	gold quality
germinal epithelium of ovary	UBERON:0001304	94.53	gold quality
palpebral conjunctiva	UBERON:0001812	93.47	gold quality
buccal mucosa cell	CL:0002336	92.90	gold quality
epithelium of nasopharynx	UBERON:0001951	92.31	gold quality
nasopharynx	UBERON:0001728	92.29	gold quality
leukocyte	CL:0000738	91.20	gold quality
monocyte	CL:0000576	91.12	gold quality
mononuclear cell	CL:0000842	91.08	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.99	gold quality
cartilage tissue	UBERON:0002418	90.93	gold quality
colonic mucosa	UBERON:0000317	90.92	gold quality
tonsil	UBERON:0002372	90.92	gold quality
endometrium	UBERON:0001295	90.88	gold quality
mammary duct	UBERON:0001765	90.52	gold quality
blood	UBERON:0000178	90.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.31	gold quality
bone marrow	UBERON:0002371	90.22	gold quality
esophagus squamous epithelium	UBERON:0006920	90.03	gold quality
trabecular bone tissue	UBERON:0002483	89.49	gold quality
bone marrow cell	CL:0002092	89.48	gold quality
epithelium of mammary gland	UBERON:0003244	89.44	gold quality
oral cavity	UBERON:0000167	89.25	gold quality
jejunal mucosa	UBERON:0000399	88.61	gold quality
corpus epididymis	UBERON:0004359	88.49	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.39	gold quality
lymph node	UBERON:0000029	88.27	gold quality
seminal vesicle	UBERON:0000998	88.19	gold quality
vermiform appendix	UBERON:0001154	88.11	gold quality
upper leg skin	UBERON:0004262	88.10	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: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
CALCA
CDH1	Repression
CDKN2B
EEF1A2
ERBB3
HP
TSC1

Upstream regulators (CollecTRI, top): EHMT2, GATA3, HIF1A, MTA3

miRNA regulators (miRDB)

177 targeting ZNF217, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 40.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• c-MYC amplification is an early event in breast cancer progression, while ZNF217 and Her2/neu amplification may play a role in the later stage of tumor development (PMID:15756435)
• ZNF217 may promote neoplastic transformation by increasing cell survival during telomeric crisis and may promote later stages of malignancy by increasing cell survival during chemotherapy. (PMID:16203743)
• These results identify a new CtBP interaction motif and establish ZNF217 as a transcriptional repressor protein that functions, at least in part, by associating with CtBP. (PMID:16940172)
• implicate ZNF217 and its associated proteins in a novel pathway that may have profound effects on cancer progression (PMID:17130829)
• ZNF217 and its associated pathways may provide new targets for therapeutic intervention in human cancers.[REVIEW] (PMID:17572303)
• Suggest that ZNF217 might play a crucial role in the proliferation and invasion of ovarian cancer. (PMID:18425333)
• These results establish the ZNF217 complex as a novel negative regulator of the p15(ink4b) gene and may constitute an important link between amplification of ZNF217 and the loss of TGF-beta responsiveness in breast cancer. (PMID:18625718)
• ZNF217 assembles a distinct set of histone modifying proteins at target DNA sites that act synergistically in transcriptional repression. (PMID:19242095)
• ZNF217 can be an important candidate gene responsible for the occurrence and progression of ovarian carcinomas. (PMID:19403395)
• ZNF217 amplification was associated with medullary breast cancer. (PMID:20429623)
• results show that ZNF217 regulates ErbB3 expression (PMID:20661224)
• Data suggest that ZNF217 might play an important role in breast neoplastic progression and chemoresistance, and that Aurora-A might be involved in ZNF217-mediated effects. (PMID:21059223)
• ZNF217 is overexpressed in GBMs and contributes to the maintenance of GSCs, which is regulated by HIFs released by the hypoxic environment of the tumor (PMID:21483406)
• multi-zinc finger protein ZNF217 contacts DNA through a two-finger domain (PMID:21908891)
• These findings indicate that ZNF217 overexpression is critical to growth and survival of OCCCs with ZNF217 gene amplification. (PMID:22139760)
• study showed that high levels of expression of ZNF217 mRNA are associated with poor prognosis and the development of metastases in breast cancer; ZNF217 also promoted epithelial-mesenchymal transition (EMT) in mammary epithelial cells (PMID:22593193)
• Data suggest that the transcription factor ZNF217 is a biomarker of poor prognosis and a therapeutic target in patients with breast cancer. (PMID:22728437)
• downregulation of miR-24ZNF17 in prostate cancer (PCa) corresponds to an upregulation of ZNF217; ZNF217 could be identified as an oncogene because it is overexpressed in prostate cancer (PCa) and affects the growth of PCa cell lines (PMID:22815235)
• found ZNF217 gene amplification to be significantly correlated with lymph node metastasis (p<0.05) in ovarian clear cell carcinoma. Profound inhibition of cell migration and invasion was observed in siRNA-treated cells with ZNF217 amplification (PMID:22843878)
• New insights into DNA recognition by zinc fingers revealed by structural analysis of the oncoprotein ZNF217. (PMID:23436653)
• Synergic effects of loss of ARID1A and PI3K-Akt pathway activation as well as ZNF217 amplification may be related to the development of ovarian clear cell carcinoma. (PMID:24336158)
• Study investigated nested regulatory circuits of miR-200c/ZEB1 and miR-200c/ZNF217/TGF-beta/ZEB1 in synergistically promoting trastuzumab resistance and metastasis of breast cancer cells. (PMID:24615544)
• ERalpha expression highly correlates with ZNF217 in lysates from breast tumors. (PMID:24962896)
• we conclude that ZNF217 may contribute to ovarian cancer invasion and metastasis, and associated with worse clinical outcomes. (PMID:25031722)
• ZNF217 expression seems to be a novel prognostic biomarker in gastric cancer. (PMID:25202062)
• Two polymorphisms in ZNF217 in Mexican patients with colorectal cancer, were studied. (PMID:25729968)
• High expression of ZNF217 is associated with enhanced cell migration and invasion in colorectal carcinoma. (PMID:25824781)
• Review: highlight the downstream molecular targets and signaling pathways of ZNF217 in tumor cells. (PMID:26431164)
• ZNF217 overexpression is associated with neoplasms. (PMID:27007163)
• findings indicate that lncRNA-ATB governs the autocrine secretion of TGF-beta2 in KFs, at least in part, by downregulating the expression level of ZNF217 via miR-200c, suggesting a signaling axis consisting of lncRNA-ATB/miR-200c/ZNF217/TGF-beta2 (PMID:27090737)
• GATA3-driven expression of miR-503 inhibits prostate cancer progression by repressing ZNF217 expression. (PMID:27267060)
• ZNF217 regulates N6-methyladenosine mRNA deposition in embryonic stem cells thus contributing to tumorigenesis by dysregulating gene expression programs. (PMID:27519282)
• this paper shows that hypoxia-inducible factors regulate pluripotency factor expression by ZNF217-mediated modulation of RNA methylation in breast cancer cells (PMID:27590511)
• this study underscored that elevated expression of ZNF217 promotes prostate cancer growth by restraining ferroportin -conducted iron egress (PMID:27768596)
• The report shows that the ZNF217 oncogene is a crucial mediator and indicator of bone metastasis from breast cancer. (PMID:28207159)
• ZNF217 contributed to ovarian hyperstimulation syndrome (OHSS) onset through promoting E2 synthesis and the increase of vascular permeability . Increased ZNF217 and decreased TSP-1 provided new targets for the prevention or treatment of OHSS (PMID:28607476)
• Indicated ZNF217 could recruit LSD1 to affect CDH1 epigenetic expression from transcription level. (PMID:30898548)
• ZNF217 inhibited both COX2 and PGE2 synthesis through estradiol in KGN cells. ZNF217 and aromatase were decreased, whereas COX2 and PGE2 were increased in the GC of women with PCOS (PMID:31454071)
• Stiff stroma increases breast cancer risk by inducing the oncogene ZNF217. (PMID:32721948)
• lncRNA SNHG1 Knockdown Alleviates Amyloid-beta-Induced Neuronal Injury by Regulating ZNF217 via Sponging miR-361-3p in Alzheimer’s Disease. (PMID:32741808)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf217	ENSDARG00000088123
mus_musculus	Zfp217	ENSMUSG00000052056
rattus_norvegicus	Zfp217	ENSRNOG00000021787

Paralogs (14): HIVEP2 (ENSG00000010818), HIVEP1 (ENSG00000095951), SALL4 (ENSG00000101115), ZNF516 (ENSG00000101493), SALL1 (ENSG00000103449), BCL11A (ENSG00000119866), ZNF831 (ENSG00000124203), RREB1 (ENSG00000124782), HIVEP3 (ENSG00000127124), BCL11B (ENSG00000127152), ZNF219 (ENSG00000165804), SALL2 (ENSG00000165821), ZNF536 (ENSG00000198597), SALL3 (ENSG00000256463)

Protein

Protein identifiers

Zinc finger protein 217 — O75362 (reviewed: O75362)

All UniProt accessions (3): O75362, A2A326, Q9BZ31

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at ‘Ser-473’.

Subunit / interactions. Component of a histone deacetylase complex that contains HDAC2, KDM1A, CTBP1 and ZNF217. May be a component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST, PHF21A/BHC80, ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Interacts with CTBP1 and CTBP2.

Subcellular location. Nucleus.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

RefSeq proteins (2): NP_001371963, NP_006517* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051967	Krueppel_C2H2-ZF	Family

Pfam: PF00096

UniProt features (37 total): modified residue 8, zinc finger region 7, compositionally biased region 7, region of interest 5, sequence variant 3, helix 2, strand 2, chain 1, cross-link 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3UK3	X-RAY DIFFRACTION	2.1
4IS1	X-RAY DIFFRACTION	2.1
4F2J	X-RAY DIFFRACTION	2.64
2HU2	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75362-F1	50.24	0.05

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 (9): 106, 321, 322, 407, 593, 648, 662, 795, 819

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription

MSigDB gene sets: 271 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, TGCACTT_MIR519C_MIR519B_MIR519A, TATTATA_MIR374, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MODULE_503, TTGCWCAAY_CEBPB_02, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_SUSTAINDED_IN_ERYTHROCYTE_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, NFKB_C, FONTAINE_PAPILLARY_THYROID_CARCINOMA_UP, MODULE_195, GENTILE_UV_RESPONSE_CLUSTER_D2, TGCTGAY_UNKNOWN, GENTILE_UV_HIGH_DOSE_DN

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (9): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): histone deacetylase complex (GO:0000118), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
ESR-mediated signaling	1
Regulation of CDH1 Gene Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
intracellular membrane-bounded organelle	2
negative regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of RNA biosynthetic process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
cation binding	1
nucleoplasm	1
nuclear protein-containing complex	1
catalytic complex	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

1496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF217	RCOR1	Q9UKL0	989
ZNF217	CTBP1	Q13363	983
ZNF217	HDAC1	Q13547	970
ZNF217	HDAC2	Q92769	968
ZNF217	HMG20B	Q9P0W2	963
ZNF217	PHF21A	Q96BD5	952
ZNF217	CTBP2	P56545	938
ZNF217	KDM1A	O60341	917
ZNF217	BCAS1	O75363	840
ZNF217	METTL3	Q86U44	755
ZNF217	ZMYM2	Q9UBW7	715
ZNF217	KLF3	P57682	669
ZNF217	KDM5B	Q9UGL1	639
ZNF217	ZNF516	Q92618	637
ZNF217	NRIP1	P48552	621

IntAct

71 interactions, top by confidence:

A	B	Type	Score
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
CTBP1	ZEB2	psi-mi:“MI:0914”(association)	0.800
CTBP1	KDM1A	psi-mi:“MI:0914”(association)	0.790
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
CTBP1	CBX4	psi-mi:“MI:0914”(association)	0.700
CTBP2	ZNF217	psi-mi:“MI:0914”(association)	0.690
DCAF7	PFDN6	psi-mi:“MI:2364”(proximity)	0.570
PIPOX	ZNF217	psi-mi:“MI:0914”(association)	0.530
CTBP2	KDM1A	psi-mi:“MI:0914”(association)	0.530
SFMBT1	KDM1A	psi-mi:“MI:0914”(association)	0.530
ZNF217	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
	ZNF217	psi-mi:“MI:0915”(physical association)	0.400
KDM1A	ZNF217	psi-mi:“MI:0915”(physical association)	0.400
ZNF217		psi-mi:“MI:0915”(physical association)	0.400
ZNF217	SREBF1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (165): ZNF217 (Affinity Capture-MS), ZNF217 (Affinity Capture-MS), ZNF217 (Affinity Capture-MS), ZNF217 (Affinity Capture-MS), ZNF217 (Affinity Capture-MS), ZNF217 (Affinity Capture-MS), ZNF217 (Affinity Capture-MS), ZNF217 (Affinity Capture-MS), ZNF217 (Affinity Capture-MS), ZNF217 (Affinity Capture-MS), KDM1A (Affinity Capture-MS), HDAC2 (Affinity Capture-MS), RCOR1 (Affinity Capture-MS), CTBP2 (Affinity Capture-MS), RCOR3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GSA2, A0A1L8H0H2, A0JP82, A0MS83, A2AWL7, A2RRX6, A2X0Q0, A6NCI8, A9ZPC9, F8VPJ6, K9JHZ4, O13186, O46567, O60284, O75362, P15822, P35547, P37275, P48552, P52551, P79269, Q03172, Q14207, Q28DZ0, Q2KHR2, Q3V0A6, Q3Y4E1, Q4JK59, Q4V7J0, Q5DTW7, Q5R782, Q5W1J6, Q5ZJK5, Q61624, Q62806, Q6N021, Q6YXZ4, Q7SZL5, Q80TY4, Q8BMA5

Diamond homologs: A1L2U9, A2A884, A2ANX9, A7Y7X5, B0X9H6, B0YDH7, B1WAZ8, B1WBU4, E9PW05, E9PZZ1, G5EBU4, O15391, O60315, O62836, O75362, O77459, O95863, P08048, P0CS62, P0CS63, P10925, P15822, P17010, P17012, P20662, P22227, P25490, P28166, P31509, P31629, P36197, P52739, P52746, P56270, P56670, P56671, P60319, P80944, Q00899, Q00900

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ZNF217	“form complex”	“CoREST-HDAC complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 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
Deactivation of the beta-catenin transactivating complex	5	25.9×	2e-04
Regulation of PTEN gene transcription	6	23.8×	4e-05
Negative Regulation of CDH1 Gene Transcription	8	21.4×	1e-06
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	10.8×	5e-03
PIP3 activates AKT signaling	7	10.4×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	20.3×	9e-04
gene expression	6	7.9×	6e-03
chromatin remodeling	6	7.2×	8e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	125
Likely benign	14
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1272 predictions. Top by Δscore:

Variant	Effect	Δscore
20:53569116:TTAC:T	donor_gain	1.0000
20:53569119:CACAA:C	donor_gain	1.0000
20:53569123:A:C	donor_gain	1.0000
20:53577282:T:A	acceptor_loss	1.0000
20:53578328:CTTTA:C	donor_loss	1.0000
20:53578329:TTTA:T	donor_loss	1.0000
20:53578330:TTAC:T	donor_loss	1.0000
20:53578331:TACCT:T	donor_loss	1.0000
20:53578332:A:T	donor_loss	1.0000
20:53578333:C:G	donor_loss	1.0000
20:53578446:TTTAT:T	acceptor_gain	1.0000
20:53578447:TTAT:T	acceptor_gain	1.0000
20:53578448:TAT:T	acceptor_gain	1.0000
20:53578449:AT:A	acceptor_gain	1.0000
20:53578449:ATCT:A	acceptor_loss	1.0000
20:53578451:C:CC	acceptor_gain	1.0000
20:53578451:CTTAA:C	acceptor_loss	1.0000
20:53578452:T:C	acceptor_gain	1.0000
20:53578452:T:TC	acceptor_gain	1.0000
20:53581455:GCTTA:G	donor_loss	1.0000
20:53581456:CTTA:C	donor_loss	1.0000
20:53581457:TTAC:T	donor_loss	1.0000
20:53581458:TACCC:T	donor_loss	1.0000
20:53581459:A:C	donor_loss	1.0000
20:53581459:AC:A	donor_gain	1.0000
20:53581460:CC:C	donor_gain	1.0000
20:53593750:CTTTA:C	donor_loss	1.0000
20:53593751:TTTAC:T	donor_loss	1.0000
20:53593752:TTACC:T	donor_loss	1.0000
20:53593753:TACCT:T	donor_loss	1.0000

AlphaMissense

6951 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:53577213:G:C	H517Q	1.000
20:53577213:G:T	H517Q	1.000
20:53577215:G:C	H517D	1.000
20:53577215:G:T	H517N	1.000
20:53577223:A:G	L514P	1.000
20:53577234:C:A	Q510H	1.000
20:53577234:C:G	Q510H	1.000
20:53577253:C:T	C504Y	1.000
20:53577263:A:G	C501R	1.000
20:53578338:A:C	H493Q	1.000
20:53578338:A:T	H493Q	1.000
20:53578340:G:C	H493D	1.000
20:53578344:T:A	R491S	1.000
20:53578344:T:G	R491S	1.000
20:53578345:C:G	R491T	1.000
20:53578348:A:G	L490P	1.000
20:53578350:A:C	H489Q	1.000
20:53578350:A:T	H489Q	1.000
20:53578352:G:C	H489D	1.000
20:53578352:G:T	H489N	1.000
20:53576582:G:C	H728D	0.999
20:53576619:A:C	C715W	0.999
20:53576620:C:T	C715Y	0.999
20:53576621:A:G	C715R	0.999
20:53576628:A:C	C712W	0.999
20:53576630:A:G	C712R	0.999
20:53577214:T:C	H517R	0.999
20:53577218:A:G	Y516H	0.999
20:53577233:T:C	K511E	0.999
20:53577235:T:G	Q510P	0.999

dbSNP variants (sampled 300 via entrez): RS1000063327 (20:53572034 A>G), RS1000090954 (20:53577432 T>C), RS1000146223 (20:53568198 C>A), RS1000164182 (20:53593011 AATCTTT>A), RS1000215499 (20:53588641 A>C), RS1000322665 (20:53592853 AAAAG>A), RS1000346020 (20:53597666 A>C), RS1000393978 (20:53573552 C>T), RS1000531146 (20:53581300 A>G), RS1000594041 (20:53583219 G>C,T), RS1000675307 (20:53597887 A>G), RS1000836685 (20:53566842 A>G), RS1000887220 (20:53566689 C>A,T), RS1001106087 (20:53587513 A>G), RS1001119348 (20:53572142 T>C)

Disease associations

OMIM: gene MIM:602967 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST001762_883	Obesity-related traits	6.000000e-06
GCST004125_21	Type 2 diabetes (age of onset)	5.000000e-06
GCST004601_199	Red blood cell count	6.000000e-11
GCST004602_235	Mean corpuscular volume	8.000000e-17
GCST004630_75	Mean corpuscular hemoglobin	2.000000e-12
GCST005038_55	Allergic disease (asthma, hay fever or eczema)	5.000000e-18
GCST007563_24	Allergic disease (asthma, hay fever or eczema)	1.000000e-11
GCST007564_16	Asthma or allergic disease (pleiotropy)	8.000000e-11
GCST007798_111	Asthma	5.000000e-10
GCST007800_84	Asthma (childhood onset)	1.000000e-07
GCST009597_157	Multiple sclerosis	2.000000e-07
GCST009615_21	Triglyceride levels x loop diuretics use interaction	9.000000e-06
GCST009719_19	Allergic rhinitis	2.000000e-08
GCST010042_144	Asthma	7.000000e-12
GCST90002385_539	High light scatter reticulocyte count	6.000000e-10
GCST90002386_519	High light scatter reticulocyte percentage of red cells	1.000000e-09
GCST90002388_584	Lymphocyte count	3.000000e-12
GCST90002396_63	Mean reticulocyte volume	4.000000e-19
GCST90002405_452	Reticulocyte count	3.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005118	IGFBP-1 measurement
EFO:0004305	erythrocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0004530	triglyceride measurement
EFO:0007986	reticulocyte count
EFO:0004587	lymphocyte count
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases abundance	3
Arsenic	affects methylation, decreases expression, increases abundance	2
Hydrogen Peroxide	affects expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
SP2509	affects binding, decreases reaction	1
FR900359	decreases phosphorylation	1
methylselenic acid	increases expression	1
arsenite	affects binding, decreases reaction	1
afimoxifene	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	increases expression	1
entinostat	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
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Fulvestrant	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Copper	affects binding, increases expression	1
Disulfiram	affects binding, increases expression	1
Doxorubicin	decreases expression	1

Cellosaurus cell lines

7 cell lines: 3 embryonic stem cell, 2 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_5534	IOSE-144RZ	Transformed cell line	Female
CVCL_5548	IOSE-80RZ	Transformed cell line	Female
CVCL_A8F3	SEES3-1V human ZNF217, clone1	Embryonic stem cell	Male
CVCL_A8F4	SEES3-1V human ZNF217, clone2	Embryonic stem cell	Male
CVCL_A8F5	SEES3-1V human ZNF217, clone3	Embryonic stem cell	Male
CVCL_E0YS	Ubigene MDA-MB-231 ZNF217 KO	Cancer cell line	Female
CVCL_VL77	FDOV1	Cancer cell line	Female

Clinical trials (associated diseases)

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