ZNF521

Summary

ZNF521 (zinc finger protein 521, HGNC:24605) is a protein-coding gene on chromosome 18q11.2, encoding Zinc finger protein 521 (Q96K83). Transcription factor that can both act as an activator or a repressor depending on the context.

Enables protein domain specific binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within neuron fate commitment. Located in nucleoplasm.

Source: NCBI Gene 25925 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 153 total
• Cancer driver (intOGen): activating (oncogene-like) across 9 cancer types
• MANE Select transcript: NM_015461

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24605
Approved symbol	ZNF521
Name	zinc finger protein 521
Location	18q11.2
Locus type	gene with protein product
Status	Approved
Aliases	EHZF, Evi3
Ensembl gene	ENSG00000198795
Ensembl biotype	protein_coding
OMIM	610974
Entrez	25925

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 5 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000361524, ENST00000399425, ENST00000538137, ENST00000577461, ENST00000577720, ENST00000577775, ENST00000577801, ENST00000579111, ENST00000580488, ENST00000581869, ENST00000582584, ENST00000583005, ENST00000583398, ENST00000584787, ENST00000897955, ENST00000897956

RefSeq mRNA: 2 — MANE Select: NM_015461 NM_001308225, NM_015461

CCDS: CCDS32806, CCDS77167

Canonical transcript exons

ENST00000361524 — 8 exons

Exon	Start	End
ENSE00001422915	25061924	25062741
ENSE00002732303	25352005	25352166
ENSE00003514626	25091950	25092081
ENSE00003542563	25350907	25350947
ENSE00003547943	25224345	25227697
ENSE00003600822	25195160	25195244
ENSE00003636853	25089465	25089580
ENSE00003677559	25322008	25322187

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 98.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.3246 / max 738.4861, expressed in 1089 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171425	11.3129	1060
171424	1.5955	383
171420	0.9149	439
171423	0.8279	230
171422	0.2079	86
171421	0.1736	74
171427	0.1210	47
171426	0.1032	36
171417	0.0440	9
171416	0.0239	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	98.20	gold quality
buccal mucosa cell	CL:0002336	97.82	gold quality
calcaneal tendon	UBERON:0003701	96.20	gold quality
cerebellum	UBERON:0002037	95.62	gold quality
cerebellar cortex	UBERON:0002129	95.45	gold quality
cerebellar hemisphere	UBERON:0002245	95.36	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.72	gold quality
tendon	UBERON:0000043	92.33	gold quality
adrenal tissue	UBERON:0018303	91.84	gold quality
pons	UBERON:0000988	91.50	gold quality
sural nerve	UBERON:0015488	91.24	gold quality
tendon of biceps brachii	UBERON:0008188	90.07	gold quality
synovial joint	UBERON:0002217	89.03	gold quality
layer of synovial tissue	UBERON:0007616	88.80	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.04	gold quality
urethra	UBERON:0000057	87.71	gold quality
ventricular zone	UBERON:0003053	87.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.19	gold quality
skin of hip	UBERON:0001554	85.71	gold quality
left ovary	UBERON:0002119	85.42	gold quality
smooth muscle tissue	UBERON:0001135	85.40	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.16	gold quality
ovary	UBERON:0000992	85.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.06	gold quality
parietal pleura	UBERON:0002400	84.86	gold quality
right ovary	UBERON:0002118	84.58	gold quality
adrenal gland	UBERON:0002369	84.48	gold quality
right adrenal gland cortex	UBERON:0035827	84.45	gold quality
thoracic mammary gland	UBERON:0005200	84.41	gold quality
mammary gland	UBERON:0001911	84.33	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.35
E-MTAB-6678	no	3.03

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
BCL2	Repression
CCND1	Repression
ZNF423

Upstream regulators (CollecTRI, top): HOXC13, SPI1, ZNF423

miRNA regulators (miRDB)

111 targeting ZNF521, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-10523-5P	99.91	69.22	2038

Literature-anchored findings (GeneRIF, showing 22)

• EHZF is likely to play a relevant role in the control of human hematopoiesis and might be implicated in the development of hematopoietic malignancies. (PMID:14630787)
• A review of possible roles for ZNF521 in development, stem cell regulation and oncogenesis. (PMID:17543573)
• ZNF521 modulates erythroid cell differentiation through direct binding with GATA-1. (PMID:19049973)
• Enhanced resistance of target cells to NK cell-mediated cytotoxicity was induced by enforced expression of EHZF in the cervical carcinoma cell line HeLa and in the B lymphoblastoid cell line IM9 (PMID:19342626)
• Zinc finger protein 521, a new player in bone formation. (PMID:20392215)
• Data show that ZNF521 can antagonize B-cell development and support the notion that it may contribute to conserve the multipotency of primitive lympho-myeloid progenitors by preventing or delaying their EBF1-driven commitment toward the B-cell lineage. (PMID:21593590)
• Data strongly support the notion that ZNF521, through the recruitment of the NuRD complex, contributes to the clonogenic growth, migration and tumorigenicity of medulloblastoma cells. (PMID:23907569)
• Newly discovered ZNF521-molecular partners of potentially relevant functional role, such as ZNF423, Spt16, Spt5, were discovered and validated by Western blotting. (PMID:25774781)
• Data show that zinc finger protein 521 (ZNF521) can function as a repressor of osteoblastic differentiation of bone marrow mesenchymal stem cells (bmMSCs). (PMID:26008984)
• two multi-zinc finger transcription cofactors named ZNF423 and ZNF521 have been characterised as potent inhibitors of EBF1 and are emerging as potentially relevant contributors to the development of B-cell leukaemias (PMID:26788497)
• Performance metrics were used to select SNPs in stage 1, which were then genotyped to another dataset (stage 2). Four SNPs (CPXM2 rs2362967, APOC1 rs4420638, ZNF521 rs7230380, and rs12965520) were identified for LOAD by both traditional P-values (without correcting for multiple tests) and performance metrics. (PMID:27805002)
• IHC based post-Ki67 levels may have distinct predictive power compared with the naive IHC Ki67. (PMID:28412727)
• knockdown of ZNF521 reduced proliferation in human leukemia cell lines possessing MLL-AF9 translocations (PMID:28615219)
• these results confirm a role for ZNF521 as a key negative regulator of adipocyte differentiation of Adipose-Derived Mesenchymal Stem Cells. (PMID:29938352)
• Together with our previous findings, these results show that ZNF521 inhibits both adipocytic and osteoblastic maturation in Human adipose-derived stem cells (hADSCs) and suggest that its expression may contribute to maintaining the immature properties of hADSCs (PMID:30567301)
• Examination of early adipogenic signals in subcutaneous adipose tissue identifies ZNF521 as a key regulator of maintaining human adipose stromal vascular fraction cells proliferative and uncommitted. Silencing ZNF521 increases BMP4 and nuclear import of the adipogenic marker and PPARgamma transcriptional activator ZNF423. (PMID:31227697)
• Zinc finger protein 521 can arrest the apoptosis and enhance the proliferation, migration, and invasion of gastric cancer cells via regulating microRNA-204-5p. Our study may provide novel clues for the treatment of patients with gastric cancer. (PMID:31526099)
• The stem cell-associated transcription co-factor, ZNF521, interacts with GLI1 and GLI2 and enhances the activity of the Sonic hedgehog pathway. (PMID:31558698)
• Regulatory Role of microRNAs Targeting the Transcription Co-Factor ZNF521 in Normal Tissues and Cancers. (PMID:34445164)
• ZNF521 Enhances MLL-AF9-Dependent Hematopoietic Stem Cell Transformation in Acute Myeloid Leukemias by Altering the Gene Expression Landscape. (PMID:34639154)
• Enhanced ZNF521 expression induces an aggressive phenotype in human ovarian carcinoma cell lines. (PMID:36191006)
• Zinc Finger 521 Modulates the Nrf2-Notch Signaling Pathway in Human Ovarian Carcinoma. (PMID:37834202)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf521	ENSDARG00000086825
danio_rerio	ZNF521	ENSDARG00000116769
mus_musculus	Zfp521	ENSMUSG00000024420
rattus_norvegicus	Zfp521	ENSRNOG00000016874
drosophila_melanogaster	CG12769	FBGN0033252
caenorhabditis_elegans		WBGENE00001223
caenorhabditis_elegans		WBGENE00017406
caenorhabditis_elegans		WBGENE00019960

Paralogs (7): ZNF423 (ENSG00000102935), ZNF211 (ENSG00000121417), ZNF462 (ENSG00000148143), ZBTB39 (ENSG00000166860), ZNF597 (ENSG00000167981), ZNF445 (ENSG00000185219), ZNF786 (ENSG00000197362)

Protein

Protein identifiers

Zinc finger protein 521 — Q96K83 (reviewed: Q96K83)

Alternative names: Early hematopoietic zinc finger protein, LYST-interacting protein 3

All UniProt accessions (7): Q96K83, H7BYU6, J3KSZ4, J3KT07, J3KTI4, J3QQI2, J3QRW6

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that can both act as an activator or a repressor depending on the context. Involved in BMP signaling and in the regulation of the immature compartment of the hematopoietic system. Associates with SMADs in response to BMP2 leading to activate transcription of BMP target genes. Acts as a transcriptional repressor via its interaction with EBF1, a transcription factor involved specification of B-cell lineage; this interaction preventing EBF1 to bind DNA and activate target genes.

Subunit / interactions. Interacts with EBF1. Interacts with SMAD1 and SMAD4.

Subcellular location. Nucleus.

Tissue specificity. Predominantly expressed in hematopoietic cells. Present in organs and tissues that contain stem and progenitor cells, myeloid and/or lymphoid: placenta, spleen, lymph nodes, thymus, bone marrow and fetal liver. Within the hematopoietic system, it is abundant in CD34(+) cells but undetectable in mature peripheral blood leukocytes, and its levels rapidly decrease during the differentiation of CD34(+) cells in response to hemopoietins.

Disease relevance. A chromosomal aberration involving ZNF521 is found in acute lymphoblastic leukemia. Translocation t(9;18)(p13;q11.2) with PAX5. The translocation generates the PAX5-ZNF521 oncogene consisting of the N-terminus part of PAX5 and the C-terminus part of ZNF521.

Domain organisation. Uses different DNA- and protein-binding zinc fingers to regulate the distinct BMP-Smad and hematopoietic system.

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

RefSeq proteins (2): NP_001295154, NP_056276* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF12874, PF13912

UniProt features (58 total): zinc finger region 30, sequence conflict 10, compositionally biased region 7, region of interest 5, modified residue 3, chain 1, site 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96K83-F1	61.75	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 72–73 (breakpoint for translocation to form pax5-znf521)

Post-translational modifications (4): 546, 605, 608, 1146

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8940973	RUNX2 regulates osteoblast differentiation
R-HSA-9823739	Formation of the anterior neural plate
R-HSA-9832991	Formation of the posterior neural plate

MSigDB gene sets: 179 (showing top): RRAGTTGT_UNKNOWN, FREAC2_01, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, FOXO4_01, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, FREAC3_01, MARTINEZ_RB1_TARGETS_DN, RIGGI_EWING_SARCOMA_PROGENITOR_DN, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, SCHAEFFER_SOX9_TARGETS_IN_PROSTATE_DEVELOPMENT_DN, TGACATY_UNKNOWN

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), neuron fate commitment (GO:0048663), cell differentiation (GO:0030154)

GO Molecular Function (5): DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein domain specific binding (GO:0019904), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Gastrulation	2
RUNX2 regulates bone development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
neuron differentiation	1
cell fate commitment	1
cellular developmental process	1
nucleic acid binding	1
transition metal ion binding	1
protein binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF521	EBF1	Q9UH73	794
ZNF521	PCBP4	P57723	620
ZNF521	GATA1	P15976	549
ZNF521	VTA1	Q9NP79	540
ZNF521	RUNX2	Q13950	512
ZNF521	SMAD4	Q13485	510
ZNF521	BMP2	P12643	502
ZNF521	BMP4	P12644	497
ZNF521	CD34	P28906	478
ZNF521	DNAJC14	Q6Y2X3	476
ZNF521	SLC16A11	Q8NCK7	446
ZNF521	GLI2	P10070	441
ZNF521	COL1A1	P02452	437
ZNF521	GLI1	P08151	419
ZNF521	CNTROB	Q8N137	419

IntAct

42 interactions, top by confidence:

A	B	Type	Score
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
ZNF219	CDK2AP1	psi-mi:“MI:0914”(association)	0.640
EIF1AD	ZNF521	psi-mi:“MI:0915”(physical association)	0.560
RARS1	ZNF521	psi-mi:“MI:0915”(physical association)	0.560
ZNF521	ZNF423	psi-mi:“MI:0915”(physical association)	0.560
MBD3L1	CDK2AP1	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
MTA1	H3C1	psi-mi:“MI:0914”(association)	0.480
ZNF521	HYOU1	psi-mi:“MI:0915”(physical association)	0.400
BRAP	ZNF521	psi-mi:“MI:0915”(physical association)	0.370
MTA1	RBBP4	psi-mi:“MI:0914”(association)	0.350
HDAC2		psi-mi:“MI:0914”(association)	0.350
ZNF17	TRIM24	psi-mi:“MI:0914”(association)	0.350
ZNF423	SPOP	psi-mi:“MI:0914”(association)	0.350
MBD3L2	AHCYL1	psi-mi:“MI:0914”(association)	0.350
BFSP2	NEK2	psi-mi:“MI:0914”(association)	0.350
ZNF423	KLHL2	psi-mi:“MI:0914”(association)	0.350
RBBP4	PHF20L1	psi-mi:“MI:0914”(association)	0.350
HDAC1	KPNA3	psi-mi:“MI:0914”(association)	0.350
ERG	BCL9	psi-mi:“MI:2364”(proximity)	0.270
FEV	TAF4	psi-mi:“MI:2364”(proximity)	0.270
HNF4A	TAF4	psi-mi:“MI:2364”(proximity)	0.270
KLF16	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (51): ZNF521 (Affinity Capture-MS), ZNF521 (Affinity Capture-MS), ZNF521 (Affinity Capture-MS), ZNF521 (Affinity Capture-MS), ZNF521 (Two-hybrid), ZNF521 (Affinity Capture-MS), ZNF521 (Affinity Capture-MS), ZNF521 (Affinity Capture-MS), ZNF521 (Affinity Capture-MS), ZNF521 (Affinity Capture-MS), ZNF521 (Affinity Capture-RNA), ZNF521 (Two-hybrid), ZNF521 (Two-hybrid), HYOU1 (Proximity Label-MS), ZNF521 (Affinity Capture-Western)

ESM2 similar proteins: A0JPB4, A1L1J6, A1L1R6, A1Z9R4, A2A935, A4IFJ6, E9Q6W4, E9Q8T2, G5E8B9, O08961, O13089, O15060, O42410, O57415, O73590, O95625, P14404, P57071, Q03112, Q03267, Q09452, Q13422, Q1L8W0, Q2M1K9, Q5DU09, Q5R9W9, Q5T0B9, Q5ZLR2, Q60821, Q62947, Q64318, Q6DBW0, Q6GNP2, Q6INV8, Q6KAS7, Q6NRM0, Q6NUD7, Q7TS63, Q802Y8, Q80TS5

Diamond homologs: A1L1R6, A1Z9R4, O08961, Q2M1K9, Q6KAS7, Q6NUD7, Q80TS5, Q96K83

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ZNF521	down-regulates	EBF1	binding
Ub:E2	“up-regulates activity”	ZNF521	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 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
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	6	73.7×	2e-08
NuRD complex assembly	9	40.9×	1e-10
RNA Polymerase I Transcription Initiation	5	36.1×	8e-06
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	6	29.5×	3e-06
Regulation of PTEN gene transcription	5	28.8×	2e-05
Interaction of NuRD complexes with transcription factors	7	28.6×	3e-07
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	5	23.6×	4e-05
HDACs deacetylate histones	6	23.3×	8e-06

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	5	98.2×	2e-07
chromatin remodeling	8	15.0×	5e-06
negative regulation of cell migration	5	14.3×	6e-04
transcription by RNA polymerase II	7	12.7×	5e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 9 cancer types — CEAD, CSCC, ESCA, HCC, LUSC, NPC, OVT, PAAD, PANCREAS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	132
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3300 predictions. Top by Δscore:

Variant	Effect	Δscore
18:25089576:AAATA:A	acceptor_gain	1.0000
18:25089577:AATA:A	acceptor_gain	1.0000
18:25089578:ATA:A	acceptor_gain	1.0000
18:25089579:TA:T	acceptor_gain	1.0000
18:25089581:C:CC	acceptor_gain	1.0000
18:25091930:T:TA	donor_gain	1.0000
18:25091944:TCCCA:T	donor_loss	1.0000
18:25091945:CCCAC:C	donor_loss	1.0000
18:25091946:CCA:C	donor_loss	1.0000
18:25091947:CA:C	donor_loss	1.0000
18:25091948:A:AT	donor_loss	1.0000
18:25091949:C:CA	donor_loss	1.0000
18:25091987:C:A	donor_gain	1.0000
18:25092077:TTCAT:T	acceptor_gain	1.0000
18:25092079:CAT:C	acceptor_gain	1.0000
18:25092080:AT:A	acceptor_gain	1.0000
18:25092081:TC:T	acceptor_loss	1.0000
18:25092082:C:A	acceptor_loss	1.0000
18:25092082:C:CC	acceptor_gain	1.0000
18:25092083:T:C	acceptor_loss	1.0000
18:25092086:C:CT	acceptor_gain	1.0000
18:25092087:A:T	acceptor_gain	1.0000
18:25131875:A:AC	donor_gain	1.0000
18:25131876:C:CC	donor_gain	1.0000
18:25195159:CCAAT:C	donor_gain	1.0000
18:25195242:CTT:C	acceptor_gain	1.0000
18:25195243:TTCTG:T	acceptor_loss	1.0000
18:25195245:C:CC	acceptor_gain	1.0000
18:25195245:CT:C	acceptor_loss	1.0000
18:25195246:T:A	acceptor_loss	1.0000

AlphaMissense

8862 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:25089469:A:G	L1301P	1.000
18:25089500:A:G	C1291R	1.000
18:25089507:A:C	C1288W	1.000
18:25089509:A:G	C1288R	1.000
18:25089559:A:G	L1271S	1.000
18:25089576:A:C	F1265L	1.000
18:25089576:A:T	F1265L	1.000
18:25089578:A:G	F1265L	1.000
18:25091957:G:C	C1261W	1.000
18:25091958:C:T	C1261Y	1.000
18:25091959:A:G	C1261R	1.000
18:25091966:A:C	C1258W	1.000
18:25091967:C:G	C1258S	1.000
18:25091967:C:T	C1258Y	1.000
18:25091968:A:G	C1258R	1.000
18:25091968:A:T	C1258S	1.000
18:25091972:G:C	F1256L	1.000
18:25091972:G:T	F1256L	1.000
18:25091974:A:G	F1256L	1.000
18:25092009:A:G	L1244P	1.000
18:25092013:G:C	H1243D	1.000
18:25092021:A:G	L1240P	1.000
18:25092050:G:C	C1230W	1.000
18:25092052:A:G	C1230R	1.000
18:25092059:G:C	C1227W	1.000
18:25092060:C:G	C1227S	1.000
18:25092061:A:G	C1227R	1.000
18:25092061:A:T	C1227S	1.000
18:25195169:G:C	H1217D	1.000
18:25195177:A:T	V1214D	1.000

dbSNP variants (sampled 300 via entrez): RS1000002648 (18:25125708 T>C), RS1000011162 (18:25338352 A>C), RS1000016662 (18:25259410 A>C), RS1000024948 (18:25300590 TA>T), RS1000035969 (18:25205532 A>G), RS1000048732 (18:25174008 C>A,T), RS1000054588 (18:25163455 G>A), RS1000060136 (18:25255296 T>A,C), RS1000083063 (18:25257940 C>A,G,T), RS1000095594 (18:25199164 T>A), RS1000095853 (18:25211000 G>A), RS1000098800 (18:25169198 A>G), RS1000106558 (18:25071462 C>G,T), RS1000115699 (18:25116053 A>G), RS1000123578 (18:25288443 G>A,C)

Disease associations

OMIM: gene MIM:610974 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001431_7	Adverse response to lamotrigine and phenytoin	6.000000e-06
GCST002616_5	Mitochondrial DNA levels	3.000000e-06
GCST002671_13	Toenail selenium levels	8.000000e-06
GCST002723_1	Urgency urinary incontinence	2.000000e-07
GCST002928_4	Nickel levels	2.000000e-06
GCST004025_11	Systemic juvenile idiopathic arthritis	2.000000e-06
GCST006575_23	Takayasu arteritis	1.000000e-06
GCST007202_6	High density lipoprotein cholesterol levels	3.000000e-06
GCST007576_65	Chronotype	6.000000e-13
GCST007643_6	Gemcitabine-induced early high-grade neutropenia in pancreatic cancer	7.000000e-06
GCST008839_569	Height	6.000000e-11
GCST011494_77	Daytime nap	1.000000e-16
GCST90000032_15	Myeloproliferative neoplasms	7.000000e-07
GCST90000047_225	Age at first sexual intercourse	5.000000e-09
GCST90000255_17	Severe COVID-19 infection with respiratory failure (analysis I)	9.000000e-06
GCST90020025_1465	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020027_179	Waist-hip index	1.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006312	mitochondrial DNA measurement
EFO:0006865	urgency urinary incontinence
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008328	chronotype measurement
EFO:0007828	daytime rest measurement
EFO:0004251	myeloproliferative disorder
EFO:0009749	age at first sexual intercourse 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	8
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
Aflatoxin B1	decreases expression, increases methylation	3
bisphenol A	increases expression, decreases expression	2
mercuric bromide	affects cotreatment, decreases expression	2
entinostat	affects cotreatment, decreases expression	2
Panobinostat	decreases expression, affects cotreatment	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentanal	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
clothianidin	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
Gemcitabine	decreases expression	1
Ethanol	decreases expression	1
Dexamethasone	decreases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Melphalan	decreases expression	1
Progesterone	decreases expression	1
Testosterone	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8I6	SEES3-1V human ZNF521, clone1	Embryonic stem cell	Male
CVCL_A8I7	SEES3-1V human ZNF521, clone2	Embryonic stem cell	Male
CVCL_A8I8	SEES3-1V human ZNF521, clone3	Embryonic stem cell	Male
CVCL_XW57	HEK293 eGFP-ZNF521	Transformed cell line	Female

Clinical trials (associated diseases)

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