ZKSCAN2

Summary

ZKSCAN2 (zinc finger with KRAB and SCAN domains 2, HGNC:25677) is a protein-coding gene on chromosome 16p12.1, encoding Zinc finger protein with KRAB and SCAN domains 2 (Q63HK3). May be involved in transcriptional regulation.

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 located in nucleus.

Source: NCBI Gene 342357 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 196 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001012981

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25677
Approved symbol	ZKSCAN2
Name	zinc finger with KRAB and SCAN domains 2
Location	16p12.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23199, ZSCAN34
Ensembl gene	ENSG00000155592
Ensembl biotype	protein_coding
Entrez	342357

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000328086, ENST00000565590, ENST00000569150, ENST00000919970, ENST00000964638

RefSeq mRNA: 1 — MANE Select: NM_001012981 NM_001012981

CCDS: CCDS32410

Canonical transcript exons

ENST00000328086 — 7 exons

Exon	Start	End
ENSE00001388151	25236001	25240738
ENSE00002301295	25256729	25257845
ENSE00003492596	25251909	25252035
ENSE00003494821	25246707	25247390
ENSE00003538871	25252946	25253037
ENSE00003549122	25243785	25244276
ENSE00003629723	25255206	25255392

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 82.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2220 / max 54.2742, expressed in 1451 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156817	3.2220	1451

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	82.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.53	gold quality
left ventricle myocardium	UBERON:0006566	81.19	gold quality
tibialis anterior	UBERON:0001385	80.97	silver quality
ventricular zone	UBERON:0003053	80.93	gold quality
cardiac muscle of right atrium	UBERON:0003379	80.93	gold quality
ganglionic eminence	UBERON:0004023	80.64	gold quality
secondary oocyte	CL:0000655	80.10	gold quality
deltoid	UBERON:0001476	75.65	silver quality
kidney epithelium	UBERON:0004819	75.65	gold quality
ileal mucosa	UBERON:0000331	75.40	silver quality
adrenal tissue	UBERON:0018303	74.06	gold quality
islet of Langerhans	UBERON:0000006	73.76	gold quality
myocardium	UBERON:0002349	73.69	gold quality
muscle tissue	UBERON:0002385	73.55	gold quality
stromal cell of endometrium	CL:0002255	73.51	gold quality
skeletal muscle tissue	UBERON:0001134	73.24	gold quality
upper arm skin	UBERON:0004263	73.07	gold quality
oocyte	CL:0000023	72.90	gold quality
cartilage tissue	UBERON:0002418	72.83	gold quality
biceps brachii	UBERON:0001507	72.57	silver quality
muscle of leg	UBERON:0001383	71.70	gold quality
gastrocnemius	UBERON:0001388	71.48	gold quality
pigmented layer of retina	UBERON:0001782	71.47	gold quality
Brodmann (1909) area 23	UBERON:0013554	70.84	silver quality
nasal cavity epithelium	UBERON:0005384	70.55	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	70.21	silver quality
hindlimb stylopod muscle	UBERON:0004252	70.09	gold quality
smooth muscle tissue	UBERON:0001135	69.91	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

118 targeting ZKSCAN2, 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-6758-5P	100.00	66.21	1470
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-204-5P	99.79	71.62	2439

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	plagx	ENSDARG00000036855
danio_rerio	ovol1a	ENSDARG00000076472
danio_rerio	plagl2	ENSDARG00000076657
danio_rerio	ovol1b	ENSDARG00000078256
mus_musculus	Zkscan2	ENSMUSG00000030757
rattus_norvegicus	Zkscan2	ENSRNOG00000024245
drosophila_melanogaster	hb	FBGN0001180
drosophila_melanogaster	CG12391	FBGN0033581
caenorhabditis_elegans		WBGENE00001824
caenorhabditis_elegans		WBGENE00003033
caenorhabditis_elegans		WBGENE00012385

Paralogs (29): ZNF446 (ENSG00000083838), REST (ENSG00000084093), ZNF174 (ENSG00000103343), OVOL3 (ENSG00000105261), PLAGL1 (ENSG00000118495), ZSCAN18 (ENSG00000121413), ZNF576 (ENSG00000124444), OVOL2 (ENSG00000125850), PLAGL2 (ENSG00000126003), ZSCAN5A (ENSG00000131848), ZSCAN29 (ENSG00000140265), ZSCAN32 (ENSG00000140987), ZSCAN1 (ENSG00000152467), ZNF18 (ENSG00000154957), ZNF496 (ENSG00000162714), ZNF202 (ENSG00000166261), ZNF641 (ENSG00000167528), ZNF444 (ENSG00000167685), SCAND1 (ENSG00000171222), ZNF274 (ENSG00000171606), ZNF131 (ENSG00000172262), OVOL1 (ENSG00000172818), ZNF518A (ENSG00000177853), ZNF518B (ENSG00000178163), PLAG1 (ENSG00000181690), ZSCAN5B (ENSG00000197213), ZNF770 (ENSG00000198146), PEG3 (ENSG00000198300), ZSCAN5C (ENSG00000204532)

Protein

Protein identifiers

Zinc finger protein with KRAB and SCAN domains 2 — Q63HK3 (reviewed: Q63HK3)

Alternative names: Zinc finger protein 694

All UniProt accessions (2): Q63HK3, H3BQ35

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q63HK3-1	1	yes
Q63HK3-2	2

RefSeq proteins (1): NP_001012999* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR003309	SCAN_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR038269	SCAN_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR044822	Myb_DNA-bind_4	Domain

Pfam: PF00096, PF01352, PF02023, PF13837

UniProt features (33 total): cross-link 10, zinc finger region 6, region of interest 3, compositionally biased region 3, sequence variant 3, domain 2, modified residue 2, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q63HK3-F1	50.63	0.03

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 (12): 591, 600, 22, 242, 259, 277, 337, 482, 529, 734, 745, 752

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 89 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, PEREZ_TP63_TARGETS, ATACCTC_MIR202, CTCTAGA_MIR526C_MIR518F_MIR526A, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM, chr16p12, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, BANP_TARGET_GENES, DIDO1_TARGET_GENES, DYRK1A_TARGET_GENES, FEV_TARGET_GENES, GLI4_TARGET_GENES, HHEX_TARGET_GENES, HMG20B_TARGET_GENES

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): 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), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic 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
transcription cis-regulatory region binding	1
transcription regulator activity	1
DNA binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZKSCAN2	SPOCD1	Q6ZMY3	543
ZKSCAN2	ZNF263	O14978	462
ZKSCAN2	DNAJC9	Q8WXX5	459
ZKSCAN2	TSPYL5	Q86VY4	434
ZKSCAN2	ZNF534	Q76KX8	414
ZKSCAN2	NHLRC4	P0CG21	399
ZKSCAN2	NKAPL	Q5M9Q1	373
ZKSCAN2	C3orf62	Q6ZUJ4	371
ZKSCAN2	ZNF777	Q9ULD5	356
ZKSCAN2	KNCN	A6PVL3	351
ZKSCAN2	ZNF282	Q9UDV7	326
ZKSCAN2	BEND4	Q6ZU67	325
ZKSCAN2	NSMCE1	Q8WV22	325
ZKSCAN2	OR1C1	Q15619	324
ZKSCAN2	KCNJ5-AS1	Q8TAV5	324

IntAct

8 interactions, top by confidence:

A	B	Type	Score
ZSCAN32	ZNF197	psi-mi:“MI:0914”(association)	0.530
CEP135	MCRIP1	psi-mi:“MI:0914”(association)	0.350
CEP135	WWP2	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
LTBP2	ZNF320	psi-mi:“MI:0914”(association)	0.350
GLI4	ZNF316	psi-mi:“MI:0914”(association)	0.350
	TTC8	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): ZKSCAN2 (Reconstituted Complex), ZKSCAN2 (Affinity Capture-RNA), ZKSCAN2 (Affinity Capture-MS), ZKSCAN2 (Affinity Capture-MS), ZKSCAN2 (Affinity Capture-MS), ZKSCAN2 (Affinity Capture-MS), ZKSCAN2 (Affinity Capture-MS), ZKSCAN2 (Cross-Linking-MS (XL-MS)), ZKSCAN2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0J9YY54, A0A494C086, A0A494C0Z2, A0A494C191, A6NHP3, A6NIY4, A6NJR5, A6NNV3, B4DH59, F6SZT2, P0C6Y7, P0CI01, P0DKJ7, P0DKJ8, P0DTA3, P0DUD1, P0DUD2, P0DUD3, P0DUD4, P0DUX0, P0DUX1, P0DV79, P79386, Q08AG5, Q13342, Q16666, Q3BBV2, Q495Y8, Q587J8, Q5JRC9, Q5QGU6, Q5RD14, Q5RKG3, Q63HK3, Q6ITT4, Q7TQI8, Q86T75, Q8IWY8, Q8N660, Q8NFV5

Diamond homologs: A0A1W2PQ72, B2KFW1, P17040, Q63HK3, Q8IWY8, Q9NX65, A1YEP8, A1YEQ3, A1YEV9, A1YFW2, A1YFW6, A1YG26, A1YG48, A1YG60, A1YGJ4, A1YGK6, A2T6E3, A2T6V8, A2T6W2, A2T712, A2T736, A2T7D2, A2T7D7, A2T7F2, A2T7F4, A2T7L7, A2T812, A6QNZ0, A6QPT6, O14709, O14771, O14978, O15535, O43309, O60304, O95125, P10073, P17022, P17028, P17029

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	166
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
830213	NC_000016.9:g.21530207_29332245del	Pathogenic

SpliceAI

1048 predictions. Top by Δscore:

Variant	Effect	Δscore
16:25243976:T:TA	donor_gain	1.0000
16:25252947:TGGG:T	donor_gain	1.0000
16:25252980:T:TA	donor_gain	1.0000
16:25253033:CCGAG:C	acceptor_gain	1.0000
16:25253034:CGAG:C	acceptor_gain	1.0000
16:25253034:CGAGC:C	acceptor_gain	1.0000
16:25253035:GAG:G	acceptor_gain	1.0000
16:25253035:GAGC:G	acceptor_loss	1.0000
16:25253036:AG:A	acceptor_gain	1.0000
16:25253036:AGCTG:A	acceptor_loss	1.0000
16:25253037:GCT:G	acceptor_loss	1.0000
16:25253038:C:CC	acceptor_gain	1.0000
16:25253039:T:A	acceptor_loss	1.0000
16:25255200:TCTTA:T	donor_loss	1.0000
16:25255201:CTTAC:C	donor_loss	1.0000
16:25255202:TTA:T	donor_loss	1.0000
16:25255203:TA:T	donor_loss	1.0000
16:25255204:ACC:A	donor_loss	1.0000
16:25255205:CCATT:C	donor_gain	1.0000
16:25255388:CTGAC:C	acceptor_gain	1.0000
16:25255391:AC:A	acceptor_gain	1.0000
16:25255391:ACCTG:A	acceptor_loss	1.0000
16:25255392:CC:C	acceptor_gain	1.0000
16:25256728:CCTG:C	donor_gain	1.0000
16:25243778:ACCTT:A	donor_loss	0.9900
16:25243779:CCTTA:C	donor_loss	0.9900
16:25243780:CTTA:C	donor_loss	0.9900
16:25243781:TTA:T	donor_loss	0.9900
16:25243782:T:TG	donor_loss	0.9900
16:25243783:A:AC	donor_gain	0.9900

AlphaMissense

6389 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:25240284:A:C	F812L	0.999
16:25240284:A:T	F812L	0.999
16:25240286:A:G	F812L	0.999
16:25240116:G:C	F868L	0.998
16:25240116:G:T	F868L	0.998
16:25240118:A:G	F868L	0.998
16:25240200:A:C	F840L	0.998
16:25240200:A:T	F840L	0.998
16:25240202:A:G	F840L	0.998
16:25244153:A:G	L538P	0.998
16:25244204:A:G	L521P	0.998
16:25244243:A:G	F508S	0.998
16:25246997:A:G	L400P	0.998
16:25239948:G:C	F924L	0.997
16:25239948:G:T	F924L	0.997
16:25239950:A:G	F924L	0.997
16:25240032:G:C	F896L	0.997
16:25240032:G:T	F896L	0.997
16:25240034:A:G	F896L	0.997
16:25244096:A:G	L557P	0.997
16:25244105:A:G	F554S	0.997
16:25247006:A:G	F397S	0.997
16:25247169:A:G	W343R	0.997
16:25247169:A:T	W343R	0.997
16:25240175:G:C	H849D	0.996
16:25240285:A:G	F812S	0.996
16:25240341:G:C	H793Q	0.996
16:25240341:G:T	H793Q	0.996
16:25240343:G:C	H793D	0.996
16:25244118:A:G	C550R	0.996

dbSNP variants (sampled 300 via entrez): RS1000024432 (16:25258326 G>C,T), RS1000094787 (16:25247949 A>T), RS1000312680 (16:25245363 T>C), RS1000407129 (16:25249010 G>A), RS1000518633 (16:25252555 A>C), RS1000623534 (16:25238870 C>T), RS1000626998 (16:25257882 G>A,C), RS1000644050 (16:25246410 A>T), RS1000729388 (16:25238302 T>G), RS1000931338 (16:25246731 G>A), RS1001098003 (16:25238621 T>C), RS1001098996 (16:25235502 G>T), RS1001183473 (16:25243669 C>A,T), RS1001194119 (16:25237343 T>C), RS1001204031 (16:25252740 CCT>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

5 associations (top):

Study	Trait	p-value
GCST007323_17	Risk-taking tendency (4-domain principal component model)	8.000000e-09
GCST007327_54	Smoking status (ever vs never smokers)	1.000000e-08
GCST007626_3	Lack of perseverance	6.000000e-07
GCST008522_59	Bitter alcoholic beverage consumption	8.000000e-07
GCST011385_5	Vaginal microbiome composition (Shannon diversity index)	9.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0006946	behavioural disinhibition measurement
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0011013	vaginal microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066418 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.03	Kd	931.6	nM	CHEMBL3752910
6.03	ED50	931.6	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149812: Binding affinity to human ZKSCAN2 incubated for 45 mins by Kinobead based pull down assay	kd	0.9316	uM

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
o,p’-DDT	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	increases expression	1
Temozolomide	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Zearalenone	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Genistein	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652854	Binding	Binding affinity to human ZKSCAN2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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