ZNF208

Summary

ZNF208 (zinc finger protein 208, HGNC:12999) is a protein-coding gene on chromosome 19p12, encoding Zinc finger protein 208 (O43345). May be involved in transcriptional regulation.

Zinc finger proteins (ZNFs), such as ZNF208, bind DNA and, through this binding, regulate gene transcription. Most ZNFs contain conserved C2H2 motifs and are classified as Kruppel-type zinc fingers. A conserved protein motif, termed the Kruppel-associated box (KRAB) domain, mediates protein-protein interactions (Eichler et al., 1998 [PubMed 9724325]). See ZNF91 (MIM 603971) for further information on ZNFs.

Source: NCBI Gene 7757 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 282 total
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_007153

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12999
Approved symbol	ZNF208
Name	zinc finger protein 208
Location	19p12
Locus type	gene with protein product
Status	Approved
Aliases	PMIDP, ZNF95
Ensembl gene	ENSG00000160321
Ensembl biotype	protein_coding
OMIM	603977
Entrez	7757

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000397126, ENST00000597040, ENST00000599723, ENST00000599916, ENST00000601773, ENST00000601993

RefSeq mRNA: 4 — MANE Select: NM_007153 NM_001329971, NM_001329973, NM_001329974, NM_007153

CCDS: CCDS54240, CCDS86734

Canonical transcript exons

ENST00000397126 — 4 exons

Exon	Start	End
ENSE00001527394	21966095	21974807
ENSE00002205895	21987216	21987311
ENSE00003466714	21988783	21988909
ENSE00003686880	22010792	22010943

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 86.47.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4133 / max 243.5364, expressed in 301 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180245	1.2977	294
180244	0.1156	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	86.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.91	gold quality
right atrium auricular region	UBERON:0006631	80.63	gold quality
heart left ventricle	UBERON:0002084	80.21	gold quality
apex of heart	UBERON:0002098	79.79	gold quality
cardiac ventricle	UBERON:0002082	79.39	gold quality
adenohypophysis	UBERON:0002196	78.94	gold quality
cardiac atrium	UBERON:0002081	78.26	gold quality
heart	UBERON:0000948	77.88	gold quality
left lobe of thyroid gland	UBERON:0001120	76.78	gold quality
islet of Langerhans	UBERON:0000006	76.57	gold quality
right testis	UBERON:0004534	76.35	gold quality
left testis	UBERON:0004533	76.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	75.69	gold quality
lower esophagus	UBERON:0013473	75.63	gold quality
pituitary gland	UBERON:0000007	75.61	gold quality
thyroid gland	UBERON:0002046	75.56	gold quality
right uterine tube	UBERON:0001302	75.50	gold quality
muscle layer of sigmoid colon	UBERON:0035805	75.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	75.10	gold quality
body of uterus	UBERON:0009853	74.90	gold quality
descending thoracic aorta	UBERON:0002345	74.85	gold quality
colonic epithelium	UBERON:0000397	74.72	gold quality
right lobe of thyroid gland	UBERON:0001119	74.72	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	74.70	gold quality
left coronary artery	UBERON:0001626	74.63	gold quality
testis	UBERON:0000473	74.53	gold quality
left uterine tube	UBERON:0001303	74.28	gold quality
thoracic aorta	UBERON:0001515	73.81	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	725.82
E-MTAB-6819	yes	329.74
E-ANND-3	no	5.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

185 targeting ZNF208, 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-3925-3P	100.00	69.95	1237
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
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-12121	99.99	66.64	255
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-23A-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 2)

• Data indicate that variants in ZNF208 are contribute to the susceptibility to esophageal cancer in a Chinese Han population. (PMID:27907911)
• three variants were associated with the risk of ischemic stroke under allele models (rs2188971, rs2188972, rs8103163 and rs7248488). The variant rs2188972 was also associated with the risk of ischemic stroke in a recessive model after adjustment for age and sex (PMID:27936511)

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf646	ENSDARG00000061424
danio_rerio	si:dkey-154p10.3	ENSDARG00000068366
danio_rerio	si:dkey-89b17.4	ENSDARG00000075545
danio_rerio	zgc:66472	ENSDARG00000075916
danio_rerio	si:ch211-148l7.4	ENSDARG00000094469
danio_rerio	znf576.1	ENSDARG00000097819
drosophila_melanogaster	Sry-delta	FBGN0003512
drosophila_melanogaster	az2	FBGN0025185
drosophila_melanogaster	hang	FBGN0026575
drosophila_melanogaster	CG3032	FBGN0029928
drosophila_melanogaster	CG2129	FBGN0030008
drosophila_melanogaster	CG11695	FBGN0030316
drosophila_melanogaster	CG8944	FBGN0030680
drosophila_melanogaster	CG7101	FBGN0030963
drosophila_melanogaster	CG1602	FBGN0033186
drosophila_melanogaster	CG18011	FBGN0033491
drosophila_melanogaster	CG12942	FBGN0033569
drosophila_melanogaster	CG8089	FBGN0033993
drosophila_melanogaster	indra	FBGN0035213
drosophila_melanogaster	CG10654	FBGN0036294
drosophila_melanogaster	CG6791	FBGN0037918
drosophila_melanogaster	CG17803	FBGN0038547
drosophila_melanogaster	CG12219	FBGN0043796
drosophila_melanogaster	CG30020	FBGN0050020
drosophila_melanogaster	pzg	FBGN0259785
drosophila_melanogaster	mld	FBGN0263490
drosophila_melanogaster	zf30C	FBGN0270924
caenorhabditis_elegans	ztf-15	WBGENE00011066
caenorhabditis_elegans		WBGENE00013734
caenorhabditis_elegans		WBGENE00015649

Paralogs (36): ZNF302 (ENSG00000089335), ZNF184 (ENSG00000096654), CTCF (ENSG00000102974), ZNF574 (ENSG00000105732), ZBTB24 (ENSG00000112365), ZNF142 (ENSG00000115568), CTCFL (ENSG00000124092), ZNF473 (ENSG00000142528), ZNF827 (ENSG00000151612), ZNF689 (ENSG00000156853), ZNF91 (ENSG00000167232), ZNF526 (ENSG00000167625), ZNF764 (ENSG00000169951), ZNF747 (ENSG00000169955), ZNF282 (ENSG00000170265), ZNF160 (ENSG00000170949), ZNF497 (ENSG00000174586), ZBTB34 (ENSG00000177125), ZNF771 (ENSG00000179965), ZNF48 (ENSG00000180035), ZNF594 (ENSG00000180626), ZBTB37 (ENSG00000185278), ZFP92 (ENSG00000189420), ZNF107 (ENSG00000196247), ZNF729 (ENSG00000196350), ZNF569 (ENSG00000196437), ZNF420 (ENSG00000197050), ZNF785 (ENSG00000197162), ZNF665 (ENSG00000197497), ZNF181 (ENSG00000197841), ZNF347 (ENSG00000197937), ZNF84 (ENSG00000198040), ZBTB48 (ENSG00000204859), ZNF845 (ENSG00000213799), ZNF99 (ENSG00000213973), ZNF688 (ENSG00000229809)

Protein

Protein identifiers

Zinc finger protein 208 — O43345 (reviewed: O43345)

Alternative names: Zinc finger protein 91-like

All UniProt accessions (6): O43345, M0QXL7, M0QYK4, M0R1F2, M0R293, M0R370

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O43345-1	1	yes
O43345-2	2

RefSeq proteins (4): NP_001316900, NP_001316902, NP_001316903, NP_009084* (*=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
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF01352, PF13465, PF13912

UniProt features (49 total): zinc finger region 39, sequence variant 5, splice variant 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43345-F1	70.22	0.01

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 71 (showing top): KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, chr19p12, MORF_EPHA7, MORF_RAB3A, MORF_WNT1, MORF_FRK, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, ATM_DN.V1_DN, PRC2_SUZ12_UP.V1_UP, HMGA1_TARGET_GENES, MIR335_3P, MIR4795_3P, MIR23A_3P_MIR23B_3P

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (3): DNA binding (GO:0003677), zinc ion binding (GO:0008270), 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
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nucleic acid binding	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF208	ACYP2	P14621	782
ZNF208	STN1	Q9H668	697
ZNF208	RTEL1	Q9NZ71	652
ZNF208	CTC1	Q2NKJ3	621
ZNF208	MPHOSPH6	Q99547	590
ZNF208	DCAF4	Q8WV16	576
ZNF208	DHX35	Q9H5Z1	575
ZNF208	PXK	Q7Z7A4	573
ZNF208	TERT	O14746	520
ZNF208	NAF1	Q96HR8	451
ZNF208	ZNF91	Q05481	433
ZNF208	SRY	Q05066	420
ZNF208	C12orf42	Q96LP6	399
ZNF208	LRRC34	Q8IZ02	351
ZNF208	POLR2F	P41584	350

IntAct

0 interactions, top by confidence:

BioGRID (1): ZNF208 (Affinity Capture-MS)

ESM2 similar proteins: A0A087WUL8, A0A0J9YWL9, A0A0U1RQI7, A6NJU9, A6NNC1, A6QL64, A7XUY5, A8MRT5, B2SU53, C9JG80, E5RHQ5, E9Q6E9, F8W0I5, O43345, O59779, O60732, P02895, P06916, P09815, P0DPF3, P13208, P13813, P14417, P20465, P20469, P21733, P32072, Q00130, Q13117, Q3BBV0, Q4ZJY7, Q4ZJZ0, Q4ZJZ1, Q4ZJZ3, Q5HY64, Q5JPF3, Q5SSG8, Q5TAG4, Q5TI25, Q63661

Diamond homologs: A0A1W2PQL4, A6NK75, A6NN14, A6NNF4, A6NP11, A8MQ14, A8MTY0, A8MUV8, A8MXY4, B4DX44, B4DXR9, E9PYI1, O14628, O43345, O75290, O75346, O75373, O75437, O95780, P0CB33, P0DKX0, P0DPD5, P16373, P17019, P17038, P21506, P35789, P52736, P52738, P52744, Q03923, Q03924, Q03936, Q03938, Q05481, Q14586, Q14593, Q14929, Q15928, Q3KNS6

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — ESCA.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	260
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

996 predictions. Top by Δscore:

Variant	Effect	Δscore
19:21974803:TATAA:T	acceptor_gain	1.0000
19:21974805:TAA:T	acceptor_gain	1.0000
19:21974808:C:CC	acceptor_gain	1.0000
19:21975301:G:C	donor_gain	1.0000
19:22010787:CTCA:C	donor_loss	1.0000
19:22010788:TCA:T	donor_loss	1.0000
19:22010789:CACCA:C	donor_loss	1.0000
19:22010790:ACC:A	donor_loss	1.0000
19:22010791:C:T	donor_loss	1.0000
19:21975300:A:AC	donor_gain	0.9900
19:22010790:A:AC	donor_gain	0.9900
19:22010790:AC:A	donor_gain	0.9900
19:22010791:C:CC	donor_gain	0.9900
19:22010791:CC:C	donor_gain	0.9900
19:22010791:CCA:C	donor_gain	0.9900
19:21974807:ACTG:A	acceptor_loss	0.9800
19:21974809:T:C	acceptor_loss	0.9800
19:21988409:G:A	donor_gain	0.9800
19:22010791:CCAT:C	donor_gain	0.9800
19:21974804:ATAA:A	acceptor_gain	0.9700
19:21974818:A:C	acceptor_loss	0.9700
19:22005193:T:TA	donor_gain	0.9700
19:21985603:A:AC	donor_gain	0.9600
19:21985604:C:CC	donor_gain	0.9600
19:22010786:ACTC:A	donor_loss	0.9600
19:22010791:CCATT:C	donor_gain	0.9600
19:21974810:G:C	acceptor_loss	0.9500
19:21985604:CT:C	donor_gain	0.9500
19:21988781:AC:A	donor_gain	0.9500
19:21988782:CC:C	donor_gain	0.9500

AlphaMissense

8553 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:21973180:A:C	F618L	0.990
19:21973180:A:T	F618L	0.990
19:21973182:A:G	F618L	0.990
19:21973516:G:C	F506L	0.989
19:21973516:G:T	F506L	0.989
19:21973518:A:G	F506L	0.989
19:21972508:A:C	F842L	0.988
19:21972508:A:T	F842L	0.988
19:21972510:A:G	F842L	0.988
19:21973432:G:C	F534L	0.988
19:21973432:G:T	F534L	0.988
19:21973434:A:G	F534L	0.988
19:21973264:A:C	F590L	0.987
19:21973264:A:T	F590L	0.987
19:21973266:A:G	F590L	0.987
19:21973012:A:C	F674L	0.986
19:21973012:A:T	F674L	0.986
19:21973014:A:G	F674L	0.986
19:21972844:A:C	F730L	0.985
19:21972844:A:T	F730L	0.985
19:21972846:A:G	F730L	0.985
19:21972676:A:C	F786L	0.983
19:21972676:A:T	F786L	0.983
19:21972678:A:G	F786L	0.983
19:21973096:A:C	F646L	0.983
19:21973096:A:T	F646L	0.983
19:21973098:A:G	F646L	0.983
19:21972928:G:C	F702L	0.982
19:21972928:G:T	F702L	0.982
19:21972930:A:G	F702L	0.982

dbSNP variants (sampled 300 via entrez): RS1000015519 (19:21999323 C>T), RS1000082829 (19:21993526 G>A), RS1000103738 (19:21959603 G>A,T), RS1000136139 (19:21959383 C>A,T), RS1000169712 (19:21984916 C>T), RS1000264470 (19:21955801 T>C), RS1000274429 (19:22005750 C>A,T), RS1000355200 (19:21950720 C>G,T), RS1000472145 (19:21982479 A>C), RS1000544289 (19:21989299 C>T), RS1000576862 (19:21989510 C>G), RS1000634962 (19:21956427 C>T), RS1000691209 (19:21951874 G>A,C), RS1000955405 (19:21978207 C>T), RS1000996734 (19:22011556 G>A)

Disease associations

OMIM: gene MIM:603977 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): CIC-rearranged sarcoma (MONDO:0956989)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002692_4	Body mass index (change over time)	3.000000e-06
GCST007267_85	Systolic blood pressure	5.000000e-10
GCST009856_11	Leukocyte telomere length	5.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005937	longitudinal BMI measurement
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation	1
Tetrachlorodibenzodioxin	decreases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02389244	PHASE2	ACTIVE_NOT_RECRUITING	A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas
NCT06414434	PHASE1	ACTIVE_NOT_RECRUITING	BTX-A51 in Patients With Liposarcoma or CIC-rearranged Sarcoma
NCT06820957	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing a New Combination of Anti-cancer Drugs in Patients Newly Diagnosed With Ewing Sarcoma Who Have Cancer That Has Spread to Other Parts of the Body