ZIK1

Summary

ZIK1 (zinc finger protein interacting with K protein 1, HGNC:33104) is a protein-coding gene on chromosome 19q13.43, encoding Zinc finger protein interacting with ribonucleoprotein K (Q3SY52). May be a transcriptional repressor.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 284307 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 80 total
• MANE Select transcript: NM_001010879

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33104
Approved symbol	ZIK1
Name	zinc finger protein interacting with K protein 1
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	ZNF762
Ensembl gene	ENSG00000171649
Ensembl biotype	protein_coding
Entrez	284307

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000307468, ENST00000536878, ENST00000597219, ENST00000597850, ENST00000598689, ENST00000598726, ENST00000599456, ENST00000600053

RefSeq mRNA: 4 — MANE Select: NM_001010879 NM_001010879, NM_001321145, NM_001321146, NM_001321147

CCDS: CCDS33135, CCDS82407, CCDS82408

Canonical transcript exons

ENST00000597850 — 4 exons

Exon	Start	End
ENSE00003021931	57584145	57584389
ENSE00003497230	57584952	57584990
ENSE00003674650	57588539	57588665
ENSE00003843186	57590011	57593890

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 87.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.4714 / max 52.0519, expressed in 1142 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177783	4.4714	1142

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.15	gold quality
ganglionic eminence	UBERON:0004023	83.88	gold quality
ventricular zone	UBERON:0003053	83.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.20	gold quality
tibialis anterior	UBERON:0001385	79.74	silver quality
cortical plate	UBERON:0005343	77.84	gold quality
islet of Langerhans	UBERON:0000006	76.92	gold quality
cardiac muscle of right atrium	UBERON:0003379	76.28	gold quality
left ventricle myocardium	UBERON:0006566	75.99	gold quality
cerebellar hemisphere	UBERON:0002245	74.27	gold quality
cerebellar cortex	UBERON:0002129	74.19	gold quality
stromal cell of endometrium	CL:0002255	73.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	73.16	gold quality
cerebellum	UBERON:0002037	72.86	gold quality
granulocyte	CL:0000094	72.18	gold quality
adrenal tissue	UBERON:0018303	71.85	gold quality
smooth muscle tissue	UBERON:0001135	71.57	gold quality
pancreatic ductal cell	CL:0002079	71.22	silver quality
ileal mucosa	UBERON:0000331	71.09	silver quality
apex of heart	UBERON:0002098	70.96	gold quality
heart left ventricle	UBERON:0002084	70.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	70.64	gold quality
secondary oocyte	CL:0000655	70.55	gold quality
lymph node	UBERON:0000029	70.54	gold quality
right lobe of thyroid gland	UBERON:0001119	70.51	gold quality
cardiac ventricle	UBERON:0002082	70.19	gold quality
oocyte	CL:0000023	69.50	gold quality
left lobe of thyroid gland	UBERON:0001120	69.49	gold quality
vermiform appendix	UBERON:0001154	69.49	gold quality
spleen	UBERON:0002106	69.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.40

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ZIK1

Upstream regulators (CollecTRI, top): ZIK1

miRNA regulators (miRDB)

116 targeting ZIK1, 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-4692	100.00	67.32	2066
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zik1	ENSMUSG00000030393
rattus_norvegicus	Zik1	ENSRNOG00000046455

Paralogs (38): ZFX (ENSG00000005889), ZBTB11 (ENSG00000066422), ZFAT (ENSG00000066827), ZFY (ENSG00000067646), ZNF586 (ENSG00000083828), IKZF5 (ENSG00000095574), ZNF419 (ENSG00000105136), ZNF549 (ENSG00000121406), ZSCAN20 (ENSG00000121903), ZNF304 (ENSG00000131845), PRDM15 (ENSG00000141956), ZNF660 (ENSG00000144792), ZNF711 (ENSG00000147180), ZNF773 (ENSG00000152439), ZNF256 (ENSG00000152454), ZNF837 (ENSG00000152475), ZNF691 (ENSG00000164011), ZNF610 (ENSG00000167554), E4F1 (ENSG00000167967), ZNF562 (ENSG00000171466), ZNF561 (ENSG00000171469), ZNF584 (ENSG00000171574), ZNF570 (ENSG00000171827), ZSCAN2 (ENSG00000176371), ZNF552 (ENSG00000178935), ZNF154 (ENSG00000179909), ZNF792 (ENSG00000180884), ZNF793 (ENSG00000188227), ZNF548 (ENSG00000188785), ZNF79 (ENSG00000196152), ZNF418 (ENSG00000196724), ZNF772 (ENSG00000197128), ZNF583 (ENSG00000198440), ZNF480 (ENSG00000198464), ZNF551 (ENSG00000204519), ZNF134 (ENSG00000213762), ZNF587B (ENSG00000269343), ZNF8 (ENSG00000278129)

Protein

Protein identifiers

Zinc finger protein interacting with ribonucleoprotein K — Q3SY52 (reviewed: Q3SY52)

Alternative names: Zinc finger protein 762

All UniProt accessions (6): Q3SY52, F5H435, M0QYP0, M0QYQ8, M0R1S7, X6R413

UniProt curated annotations — full annotation on UniProt →

Function. May be a transcriptional repressor.

Subunit / interactions. Interacts with HNRPK.

Subcellular location. Nucleus.

Tissue specificity. Expressed at high levels in gastric glands, and at low levels in colon and small intestine. Silenced through promoter methylation in gastric glands with intestinal metaplasia.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q3SY52-1	1	yes
Q3SY52-2	2
Q3SY52-3	3

RefSeq proteins (4): NP_001010879, NP_001308074, NP_001308075, NP_001308076 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050589	Ikaros_C2H2-ZF	Family
IPR056436	Znf-C2H2_ZIC1-5/GLI1-3-like	Domain

Pfam: PF00096, PF01352, PF23561

UniProt features (16 total): zinc finger region 9, splice variant 2, chain 1, domain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3SY52-F1	65.87	0.44

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 81 (showing top): GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, ZHANG_BREAST_CANCER_PROGENITORS_UP, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MEISSNER_ES_ICP_WITH_H3K4ME3, MEISSNER_NPC_ICP_WITH_H3K4ME3, MEISSNER_BRAIN_ICP_WITH_H3K4ME3, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_QTL_TRANS, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GCNP_SHH_UP_LATE.V1_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GSE14415_INDUCED_TREG_VS_FAILED_INDUCED_TREG_UP, CEBPZ_TARGET_GENES

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355), regulation of macromolecule metabolic process (GO:0060255), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of metabolic process	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
macromolecule metabolic process	1
primary metabolic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZIK1	WFDC12	Q8WWY7	537
ZIK1	PNMA5	Q96PV4	534
ZIK1	EOLA2	Q96DE9	479
ZIK1	GJA9	P57773	436
ZIK1	IRGQ	Q8WZA9	411
ZIK1	KRTAP6-3	Q3LI67	393
ZIK1	PNMA3	Q9UL41	390
ZIK1	RTL8A	Q9BWD3	352
ZIK1	OR1Q1	Q15612	328
ZIK1	MS4A3	Q96HJ5	311
ZIK1	PRAMEF10	O60809	310
ZIK1	SDR42E1	Q8WUS8	310
ZIK1	CCDC7	Q96M83	305
ZIK1	WDR17	Q8IZU2	272
ZIK1	CCSAP	Q6IQ19	270
ZIK1	C21orf91	Q9NYK6	270

IntAct

8 interactions, top by confidence:

A	B	Type	Score
ZIK1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
ZIK1	H2BC20P	psi-mi:“MI:0915”(physical association)	0.400
ZIK1	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
ECE1	ZIK1	psi-mi:“MI:0915”(physical association)	0.370
ZKSCAN3	IPO8	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): ZIK1 (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), CCDC73 (Cross-Linking-MS (XL-MS)), ZIK1 (Affinity Capture-MS)

ESM2 similar proteins: A0JPL0, A6NK53, E7ETH6, E9Q8G5, O14628, P21506, P51508, Q09FC8, Q13360, Q2M218, Q2M3X9, Q2VY69, Q3KQV3, Q3SY52, Q4R882, Q5HY98, Q5REN4, Q5RES8, Q68DI1, Q6NX49, Q6P280, Q6PG37, Q6V9R5, Q6ZMW2, Q7Z340, Q86XU0, Q8IYI8, Q8N587, Q8N720, Q8N859, Q8NB42, Q8NDW4, Q8NEK5, Q8WXB4, Q96MR9, Q96MU6, Q96NG8, Q96NJ3, Q96SR6, Q9BR84

Diamond homologs: A2RRD8, A6NFI3, A6NM28, A8MUZ8, A8MWA4, B2RUI1, B4DU55, E9Q8G5, O43296, O43361, O75467, O75820, P0CH99, P0CI00, P10078, P16373, P16374, P17021, P17023, P17032, P17097, P17098, P21506, P51786, P52740, Q06732, Q08ER8, Q13106, Q13360, Q13398, Q14592, Q147U1, Q32M78, Q3KQV3, Q3MIS6, Q3SY52, Q571J5, Q5CZA5, Q5HY98, Q5R7I8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

669 predictions. Top by Δscore:

Variant	Effect	Δscore
19:57578562:AGT:A	donor_gain	0.9900
19:57584386:TCAGG:T	donor_loss	0.9900
19:57584387:CAGG:C	donor_loss	0.9900
19:57584388:AGGT:A	donor_loss	0.9900
19:57584389:GGTG:G	donor_loss	0.9900
19:57584390:G:C	donor_loss	0.9900
19:57584391:T:A	donor_loss	0.9900
19:57584988:AAGGT:A	donor_loss	0.9900
19:57584991:G:C	donor_loss	0.9900
19:57584992:TGAGT:T	donor_loss	0.9900
19:57584993:GAGTG:G	donor_loss	0.9900
19:57588664:GG:G	donor_gain	0.9900
19:57588665:GG:G	donor_gain	0.9900
19:57589631:T:A	acceptor_gain	0.9900
19:57589632:G:A	acceptor_gain	0.9900
19:57578560:ATAGT:A	donor_gain	0.9800
19:57578665:CACT:C	donor_loss	0.9800
19:57578666:ACTC:A	donor_loss	0.9800
19:57578667:CT:C	donor_loss	0.9800
19:57578668:TCA:T	donor_loss	0.9800
19:57578669:CAC:C	donor_loss	0.9800
19:57578670:A:AC	donor_gain	0.9800
19:57578670:ACCG:A	donor_loss	0.9800
19:57578671:C:CC	donor_gain	0.9800
19:57578671:C:G	donor_loss	0.9800
19:57588538:GGGCT:G	acceptor_gain	0.9800
19:57588666:G:GT	donor_loss	0.9800
19:57588667:TAA:T	donor_loss	0.9800
19:57578664:GCACT:G	donor_loss	0.9700
19:57584222:G:GT	donor_gain	0.9700

AlphaMissense

3226 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:57590805:T:C	F332L	0.997
19:57590807:T:A	F332L	0.997
19:57590807:T:G	F332L	0.997
19:57590889:T:C	F360L	0.997
19:57590891:T:A	F360L	0.997
19:57590891:T:G	F360L	0.997
19:57591057:T:C	F416L	0.997
19:57591059:T:A	F416L	0.997
19:57591059:T:G	F416L	0.997
19:57591141:T:C	F444L	0.997
19:57591143:T:A	F444L	0.997
19:57591143:T:G	F444L	0.997
19:57590973:T:C	F388L	0.996
19:57590975:T:A	F388L	0.996
19:57590975:T:G	F388L	0.996
19:57590750:C:A	H313Q	0.994
19:57590750:C:G	H313Q	0.994
19:57590666:T:A	H285Q	0.993
19:57590666:T:G	H285Q	0.993
19:57590721:T:C	F304L	0.993
19:57590723:T:A	F304L	0.993
19:57590723:T:G	F304L	0.993
19:57590637:T:C	F276L	0.991
19:57590639:T:A	F276L	0.991
19:57590639:T:G	F276L	0.991
19:57590656:T:C	L282P	0.991
19:57590834:C:A	H341Q	0.991
19:57590834:C:G	H341Q	0.991
19:57591225:T:C	F472L	0.991
19:57591227:T:A	F472L	0.991

dbSNP variants (sampled 300 via entrez): RS1000161227 (19:57587398 AGT>A), RS1000258902 (19:57593891 CTT>C), RS1000293520 (19:57593560 C>T), RS1000854710 (19:57592242 C>T), RS1000898301 (19:57588817 T>C), RS1001067705 (19:57585619 G>T), RS1001107193 (19:57582485 GGTT>G), RS1001649938 (19:57582464 T>C), RS1001909698 (19:57589229 G>A), RS1002200545 (19:57582457 A>G), RS1002231521 (19:57582170 G>A), RS1002333702 (19:57584077 C>A,G,T), RS1002916162 (19:57591897 G>A), RS1003080302 (19:57585254 C>T), RS1003176506 (19:57587514 A>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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	decreases expression, increases methylation	1
tobacco tar	decreases expression	1
lei gong teng	increases expression	1
epigallocatechin gallate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	decreases methylation	1
Smoke	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XV99	HEK293 eGFP-ZIK1	Transformed cell line	Female

Clinical trials (associated diseases)

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