ZNF197

Summary

ZNF197 (zinc finger protein 197, HGNC:12988) is a protein-coding gene on chromosome 3p21.31, encoding Zinc finger protein 197 (O14709). May be involved in transcriptional regulation.

This gene product belongs to the zinc finger protein superfamily, members of which are regulatory proteins characterized by nucleic acid-binding zinc finger domains. The encoded protein contains 20 tandemly arrayed C2H2-type zinc fingers, a Kruppel-associated box (KRAB) domain, and a SCAN box. This transcript turns over rapidly and contains 3’ UTR AUUUA motifs, which are often a hallmark of rapid turnover. It is overexpressed in some thyroid papillary carcinomas. This gene is located in a cluster of zinc finger genes at 3p21. Naturally-occurring readthrough transcription is observed between this gene and the upstream zinc finger protein 660 gene and is represented by GeneID:110354863.

Source: NCBI Gene 10168 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_006991

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12988
Approved symbol	ZNF197
Name	zinc finger protein 197
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	P18, D3S1363E, ZKSCAN9, ZSCAN41
Ensembl gene	ENSG00000186448
Ensembl biotype	protein_coding
OMIM	618359
Entrez	10168

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000334075, ENST00000344387, ENST00000383744, ENST00000383745, ENST00000396058, ENST00000412641, ENST00000894446, ENST00000934426

RefSeq mRNA: 10 — MANE Select: NM_006991 NM_001024855, NM_001323293, NM_001323294, NM_001323295, NM_001323296, NM_001351732, NM_001351733, NM_001351734, NM_001351735, NM_006991

Canonical transcript exons

ENST00000344387 — 6 exons

Exon	Start	End
ENSE00001498449	44629074	44629544
ENSE00001847235	44625036	44625143
ENSE00001874065	44641900	44648471
ENSE00003514584	44632473	44632599
ENSE00003635524	44632105	44632196
ENSE00003640827	44631062	44631221

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 90.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.6646 / max 136.6362, expressed in 1791 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36337	9.4123	1763
36338	3.5522	1462
36336	0.9570	644
36333	0.7431	422

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	90.43	gold quality
ganglionic eminence	UBERON:0004023	88.51	gold quality
ventricular zone	UBERON:0003053	85.53	gold quality
calcaneal tendon	UBERON:0003701	83.80	gold quality
corpus callosum	UBERON:0002336	83.67	gold quality
skeletal muscle tissue	UBERON:0001134	83.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.84	gold quality
islet of Langerhans	UBERON:0000006	82.80	gold quality
muscle tissue	UBERON:0002385	82.50	gold quality
adrenal tissue	UBERON:0018303	81.51	gold quality
gastrocnemius	UBERON:0001388	81.42	gold quality
muscle of leg	UBERON:0001383	81.28	gold quality
endometrium	UBERON:0001295	81.22	gold quality
stromal cell of endometrium	CL:0002255	80.27	gold quality
colonic epithelium	UBERON:0000397	80.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.89	gold quality
smooth muscle tissue	UBERON:0001135	78.83	gold quality
sural nerve	UBERON:0015488	78.80	gold quality
urinary bladder	UBERON:0001255	78.20	gold quality
mucosa of stomach	UBERON:0001199	78.13	gold quality
tonsil	UBERON:0002372	78.04	gold quality
pancreas	UBERON:0001264	77.87	gold quality
cerebellar cortex	UBERON:0002129	77.56	gold quality
cerebellum	UBERON:0002037	77.50	gold quality
cerebellar hemisphere	UBERON:0002245	77.47	gold quality
rectum	UBERON:0001052	76.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	76.91	gold quality
ovary	UBERON:0000992	76.87	gold quality
primary visual cortex	UBERON:0002436	76.85	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	14.76
E-ANND-3	no	0.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting ZNF197, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-628-3P	99.04	68.37	814
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-9986	98.91	69.28	1024

Literature-anchored findings (GeneRIF, showing 1)

• a novel pVHL-interacting protein that functions as a negative regulator of hypoxia-inducible factor-1a (HIF-1alpha) transactivation; demonstrate that the KRAB-A domain in VHLaK mediates pVHL binding and functions as a transcriptional repression module (PMID:12682018)

Cross-species orthologs

0 orthologs

Paralogs (176): ZNF195 (ENSG00000005801), ZNF112 (ENSG00000062370), ZNF275 (ENSG00000063587), ZNF37A (ENSG00000075407), ZNF510 (ENSG00000081386), ZNF506 (ENSG00000081665), ZNF268 (ENSG00000090612), MZF1 (ENSG00000099326), ZNF629 (ENSG00000102870), ZNF175 (ENSG00000105497), ZNF85 (ENSG00000105750), ZFP30 (ENSG00000120784), ZNF45 (ENSG00000124459), ZNF391 (ENSG00000124613), ZNF436 (ENSG00000125945), ZNF484 (ENSG00000127081), ZNF835 (ENSG00000127903), ZNF780B (ENSG00000128000), ZSCAN10 (ENSG00000130182), ZNF317 (ENSG00000130803), ZNF331 (ENSG00000130844), ZNF227 (ENSG00000131115), ZNF141 (ENSG00000131127), ZNF132 (ENSG00000131849), ZNF189 (ENSG00000136870), ZIM3 (ENSG00000141946), ZFP14 (ENSG00000142065), ZNF514 (ENSG00000144026), ZNF300 (ENSG00000145908), RBAK (ENSG00000146587), ZNF157 (ENSG00000147117), ZNF182 (ENSG00000147118), ZNF41 (ENSG00000147124), ZNF7 (ENSG00000147789), ZNF117 (ENSG00000152926), ZNF221 (ENSG00000159905), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631)

Protein

Protein identifiers

Zinc finger protein 197 — O14709 (reviewed: O14709)

Alternative names: Zinc finger protein with KRAB and SCAN domains 9, ZnF20, pVHL-associated KRAB domain-containing protein

All UniProt accessions (3): O14709, C9JQH5, F8WEU5

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

Miscellaneous. Negative regulator of HIF1A transactivation.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O14709-1	1	yes
O14709-2	2, VHLaK

RefSeq proteins (10): NP_001020026, NP_001310222, NP_001310223, NP_001310224, NP_001310225, NP_001338661, NP_001338662, NP_001338663, NP_001338664, NP_008922* (*=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
IPR050752	C2H2-ZF_domain	Family

Pfam: PF00096, PF01352, PF02023

UniProt features (28 total): zinc finger region 22, domain 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14709-F1	69.41	0.03

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 55 (showing top): GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chr3p21, DIDO1_TARGET_GENES, NFE2L1_TARGET_GENES, SNIP1_TARGET_GENES, SOX10_TARGET_GENES, ZBTB12_TARGET_GENES, ZNF362_TARGET_GENES, ZNF711_TARGET_GENES, ZNF830_TARGET_GENES, MIR153_5P, MIR3662, MIR335_3P, MIR4659A_3P_MIR4659B_3P, MIR4307

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

GO Molecular Function (4): zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), 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 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
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF197	POLR2G	P52433	441
ZNF197	PHB2	Q99623	418
ZNF197	CD53	P19397	416
ZNF197	TUSC1	Q2TAM9	413
ZNF197	ANTXR1	Q9H6X2	408
ZNF197	TMBIM6	P55061	404
ZNF197	FIGN	Q5HY92	396
ZNF197	BCL2L11	O43521	391
ZNF197	ZNF398	Q8TD17	379
ZNF197	TCERG1	O14776	374
ZNF197	POLR2A	P24928	373
ZNF197	YPEL3	P61236	373
ZNF197	ACOT13	Q9NPJ3	371
ZNF197	PCMT1	P22061	368
ZNF197	UGGT2	Q9NYU1	368

IntAct

33 interactions, top by confidence:

A	B	Type	Score
ZSCAN32	ZNF197	psi-mi:“MI:0914”(association)	0.530
ZNF397	ZNF197	psi-mi:“MI:0914”(association)	0.530
ZNF483	ZNF197	psi-mi:“MI:0914”(association)	0.530
ZNF689	ZNF593	psi-mi:“MI:0914”(association)	0.530
ZNF197	BCAP29	psi-mi:“MI:0915”(physical association)	0.400
ZNF197	SPTAN1	psi-mi:“MI:0915”(physical association)	0.400
ZNF197	TRIM28	psi-mi:“MI:0915”(physical association)	0.400
HSPB1	ZNF197	psi-mi:“MI:0915”(physical association)	0.370
Set	ZKSCAN1	psi-mi:“MI:0914”(association)	0.350
PB2		psi-mi:“MI:0914”(association)	0.350
CCDC136	CCDC85C	psi-mi:“MI:0914”(association)	0.350
ZSCAN20	ZNF197	psi-mi:“MI:0914”(association)	0.350
ZNF232	ZNF197	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ZNF197	DISC1	psi-mi:“MI:0915”(physical association)	0.000
ZNF197	NDEL1	psi-mi:“MI:0915”(physical association)	0.000
EPHA1	ZNF197	psi-mi:“MI:0915”(physical association)	0.000
DISC1	ZNF197	psi-mi:“MI:0915”(physical association)	0.000
APP	ZNF197	psi-mi:“MI:0915”(physical association)	0.000
NDEL1	ZNF197	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): ZNF197 (Affinity Capture-MS), ZNF197 (Affinity Capture-MS), ZNF197 (Affinity Capture-MS), ZNF197 (Two-hybrid), ZNF197 (Affinity Capture-MS), ZNF197 (Affinity Capture-MS), ZNF197 (Affinity Capture-MS), ZNF197 (Affinity Capture-MS), ZNF197 (Affinity Capture-MS), ZNF197 (Affinity Capture-MS), ZNF197 (Affinity Capture-MS), ZNF197 (Two-hybrid), ZNF197 (Reconstituted Complex), ZNF197 (Affinity Capture-Western), ZNF197 (Affinity Capture-Western)

ESM2 similar proteins: A0JNB1, A1YF12, A1YG88, A2T759, A6QLU5, B2RUI1, D3ZVT0, O14709, O43296, O75123, P10072, P15621, P17020, P17097, P51814, P85977, Q08ER8, Q0VGE8, Q14590, Q32KN0, Q3KQV3, Q4V8A8, Q5CZA5, Q5RBX0, Q5RCD9, Q5VIY5, Q61116, Q61967, Q6GQR8, Q6P9A3, Q6ZMS4, Q7TSH9, Q7TSI0, Q7Z3I7, Q86UD4, Q86WZ6, Q8BFS8, Q8IZ26, Q8N9F8, Q8TAF7

Diamond homologs: A1YEP8, A1YEQ3, A1YEV9, A1YFW2, A1YFW6, A1YG26, A1YG48, A1YG60, A1YGJ4, A1YGK6, A2T6E3, A2T6V8, A2T6W2, A2T712, A2T736, A2T7D2, A2T7D7, A2T7F2, A2T7F4, A2T7L7, A2T812, A6QNZ0, A6QPT6, B2KFW1, O14709, O14771, O14978, O15535, O43309, O60304, O95125, P10073, P17022, P17028, P17029, P17040, P28698, P49910, P51815, P59923

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1230 predictions. Top by Δscore:

Variant	Effect	Δscore
3:44586103:A:AG	acceptor_gain	1.0000
3:44586104:G:GG	acceptor_gain	1.0000
3:44625144:G:C	donor_loss	1.0000
3:44625145:T:A	donor_loss	1.0000
3:44629541:ACAAG:A	donor_loss	1.0000
3:44629542:CAAGT:C	donor_loss	1.0000
3:44629544:AG:A	donor_loss	1.0000
3:44629545:G:GG	donor_gain	1.0000
3:44631217:GCATG:G	donor_gain	1.0000
3:44632466:A:AG	acceptor_gain	1.0000
3:44632467:TTTCA:T	acceptor_loss	1.0000
3:44632468:TTCA:T	acceptor_loss	1.0000
3:44632469:TCA:T	acceptor_loss	1.0000
3:44632471:A:AG	acceptor_gain	1.0000
3:44632472:G:GA	acceptor_gain	1.0000
3:44632472:GGA:G	acceptor_gain	1.0000
3:44632472:GGAGT:G	acceptor_gain	1.0000
3:44632597:TAGGT:T	donor_loss	1.0000
3:44632599:GGT:G	donor_loss	1.0000
3:44632600:G:GG	donor_gain	1.0000
3:44632600:GTAAG:G	donor_loss	1.0000
3:44632601:T:G	donor_loss	1.0000
3:44586103:AGT:A	acceptor_gain	0.9900
3:44586104:GT:G	acceptor_gain	0.9900
3:44586104:GTG:G	acceptor_gain	0.9900
3:44586212:GG:G	donor_gain	0.9900
3:44586213:GG:G	donor_gain	0.9900
3:44587236:G:GT	donor_gain	0.9900
3:44587251:G:GG	donor_gain	0.9900
3:44625144:G:GG	donor_gain	0.9900

AlphaMissense

6903 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:44642349:T:C	F407L	1.000
3:44642351:T:A	F407L	1.000
3:44642351:T:G	F407L	1.000
3:44642433:T:C	F435L	1.000
3:44642435:T:A	F435L	1.000
3:44642435:T:G	F435L	1.000
3:44642452:T:C	L441P	1.000
3:44642460:C:G	H444D	1.000
3:44642462:T:A	H444Q	1.000
3:44642462:T:G	H444Q	1.000
3:44642517:T:C	F463L	1.000
3:44642519:C:A	F463L	1.000
3:44642519:C:G	F463L	1.000
3:44642536:T:C	L469P	1.000
3:44643357:T:C	F743L	1.000
3:44643359:C:A	F743L	1.000
3:44643359:C:G	F743L	1.000
3:44643441:T:C	F771L	1.000
3:44643443:C:A	F771L	1.000
3:44643443:C:G	F771L	1.000
3:44643460:T:C	L777P	1.000
3:44643693:T:C	F855L	1.000
3:44643694:T:C	F855S	1.000
3:44643695:T:A	F855L	1.000
3:44643695:T:G	F855L	1.000
3:44643861:T:C	F911L	1.000
3:44643863:T:A	F911L	1.000
3:44643863:T:G	F911L	1.000
3:44643880:T:C	L917P	1.000
3:44632506:T:C	F226L	0.999

dbSNP variants (sampled 300 via entrez): RS1000221208 (3:44639006 G>A,C), RS1000233234 (3:44639392 C>A), RS1000343534 (3:44631946 C>A), RS1000597474 (3:44625127 C>T), RS1000826160 (3:44631808 C>T), RS1000924911 (3:44647485 CA>C), RS1000953859 (3:44647912 A>G), RS1001096334 (3:44625942 T>C,G), RS1001152781 (3:44640644 C>T), RS1001380798 (3:44630541 T>C), RS1001384063 (3:44645509 T>C), RS1001415301 (3:44645764 C>G), RS1001458223 (3:44640254 A>C), RS1001581910 (3:44625797 A>G), RS1001922829 (3:44625448 A>G)

Disease associations

OMIM: gene MIM:618359 | 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
entinostat	decreases expression, affects cotreatment	2
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	increases methylation, decreases expression	1
sodium arsenite	decreases expression	1
cupric chloride	affects expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	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
dorsomorphin	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	affects expression	1
Dimethyl Sulfoxide	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Valproic Acid	decreases methylation	1
Cyclosporine	increases expression	1
Asbestos, Serpentine	decreases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	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_HA01	K562 eGFP-ZNF197	Cancer cell line	Female

Clinical trials (associated diseases)

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