ZNF215

Summary

ZNF215 (zinc finger protein 215, HGNC:13007) is a protein-coding gene on chromosome 11p15.4, encoding Zinc finger protein 215 (Q9UL58). May be involved in transcriptional regulation.

This gene is imprinted in a tissue-specific manner with preferential expression in the testis, and encodes a zinc finger protein that belongs to a family of zinc finger transcription factors. The encoded protein contains an N-terminal SRE-ZBP, Ctfin51, AW-1, and Number 18 (SCAN) domain, a kruppel-associated box A (KRABA) domain, and four C-terminal zinc finger domains. This gene is located within one of three regions on chromosome 11p15 associated with Beckwith-Wiedemann syndrome, called Beckwith-Wiedemann syndrome chromosome region-2 (BWSCR2), and is thought to play a role in the etiology of this disease.

Source: NCBI Gene 7762 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Beckwith-Wiedemann syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 100 total
• MANE Select transcript: NM_013250

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13007
Approved symbol	ZNF215
Name	zinc finger protein 215
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	ZKSCAN11, ZSCAN43
Ensembl gene	ENSG00000149054
Ensembl biotype	protein_coding
OMIM	605016
Entrez	7762

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 13 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000278319, ENST00000414517, ENST00000527171, ENST00000529755, ENST00000529903, ENST00000532533, ENST00000610573, ENST00000636097, ENST00000636606, ENST00000864177, ENST00000864178, ENST00000864179, ENST00000921286, ENST00000921287, ENST00000921288, ENST00000921289, ENST00000921290, ENST00000921291

RefSeq mRNA: 9 — MANE Select: NM_013250 NM_001354853, NM_001354854, NM_001354855, NM_001354856, NM_001354857, NM_001354858, NM_001354859, NM_001354860, NM_013250

CCDS: CCDS7775, CCDS86177

Canonical transcript exons

ENST00000278319 — 7 exons

Exon	Start	End
ENSE00001036864	6927662	6927807
ENSE00001102437	6943083	6943215
ENSE00002159361	6955690	6958047
ENSE00003484544	6932094	6932672
ENSE00003623380	6941571	6941653
ENSE00003672108	6943546	6943641
ENSE00003841747	6926426	6926685

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 94.24.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0835 / max 44.3196, expressed in 791 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112881	1.4627	544
112880	0.6209	366

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.24	gold quality
oocyte	CL:0000023	93.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.18	gold quality
bone marrow cell	CL:0002092	77.31	gold quality
colonic epithelium	UBERON:0000397	76.26	gold quality
stromal cell of endometrium	CL:0002255	73.98	gold quality
rectum	UBERON:0001052	72.52	gold quality
body of pancreas	UBERON:0001150	70.28	gold quality
olfactory bulb	UBERON:0002264	69.52	gold quality
type B pancreatic cell	CL:0000169	69.46	gold quality
mucosa of transverse colon	UBERON:0004991	68.94	gold quality
lymph node	UBERON:0000029	67.74	gold quality
pancreas	UBERON:0001264	67.03	gold quality
cortical plate	UBERON:0005343	66.47	gold quality
tonsil	UBERON:0002372	66.40	gold quality
transverse colon	UBERON:0001157	66.31	gold quality
diaphragm	UBERON:0001103	65.80	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.75	gold quality
calcaneal tendon	UBERON:0003701	65.27	gold quality
ventricular zone	UBERON:0003053	65.00	gold quality
duodenum	UBERON:0002114	64.98	gold quality
smooth muscle tissue	UBERON:0001135	64.96	gold quality
small intestine	UBERON:0002108	64.64	gold quality
metanephros cortex	UBERON:0010533	64.57	gold quality
minor salivary gland	UBERON:0001830	63.81	gold quality
embryo	UBERON:0000922	63.66	gold quality
islet of Langerhans	UBERON:0000006	63.63	gold quality
spleen	UBERON:0002106	63.36	gold quality
ganglionic eminence	UBERON:0004023	63.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.40

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2547.1	ZNF215	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605530

Upstream regulators (CollecTRI, top): TP53

Literature-anchored findings (GeneRIF, showing 2)

• Loss of ZNF215 imprinting is associated with poor five-year survival in patients with cytogenetically abnormal-acute myeloid leukemia. (PMID:34091126)
• CircZNF215 promotes tumor growth and metastasis through inactivation of the PTEN/AKT pathway in intrahepatic cholangiocarcinoma. (PMID:37198696)

Cross-species orthologs

0 orthologs

Paralogs (30): ZNF263 (ENSG00000006194), ZNF213 (ENSG00000085644), ZNF500 (ENSG00000103199), ZKSCAN1 (ENSG00000106261), ZNF205 (ENSG00000122386), ZSCAN9 (ENSG00000137185), PGBD1 (ENSG00000137338), ZSCAN12 (ENSG00000158691), ZNF394 (ENSG00000160908), ZNF75A (ENSG00000162086), ZSCAN21 (ENSG00000166529), ZNF232 (ENSG00000167840), ZNF24 (ENSG00000172466), ZNF449 (ENSG00000173275), ZSCAN4 (ENSG00000180532), ZSCAN22 (ENSG00000182318), ZNF75D (ENSG00000186376), ZNF396 (ENSG00000186496), ZNF397 (ENSG00000186812), ZSCAN30 (ENSG00000186814), ZKSCAN4 (ENSG00000187626), ZSCAN23 (ENSG00000187987), ZKSCAN3 (ENSG00000189298), ZSCAN16 (ENSG00000196812), ZSCAN25 (ENSG00000197037), ZSCAN26 (ENSG00000197062), ZNF165 (ENSG00000197279), ZKSCAN8 (ENSG00000198315), ZSCAN31 (ENSG00000235109), ZNF853 (ENSG00000236609)

Protein

Protein identifiers

Zinc finger protein 215 — Q9UL58 (reviewed: Q9UL58)

Alternative names: BWSCR2-associated zinc finger protein 2, Zinc finger protein with KRAB and SCAN domains 11

All UniProt accessions (3): Q9UL58, A0A1B0GV37, B4DYW9

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?
Q9UL58-1	1	yes
Q9UL58-2	2

RefSeq proteins (9): NP_001341782, NP_001341783, NP_001341784, NP_001341785, NP_001341786, NP_001341787, NP_001341788, NP_001341789, NP_037382* (*=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 (15 total): sequence variant 6, zinc finger region 4, domain 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UL58-F1	49.68	0.00

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 60 (showing top): PODAR_RESPONSE_TO_ADAPHOSTIN_UP, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A12, ATM_DN.V1_UP, MYC_UP.V1_UP, PRC2_EZH2_UP.V1_UP, IL15_UP.V1_UP, IL2_UP.V1_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR95_5P, MIR32_3P, MIR4528, MIR486_3P, MIR4679

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355), negative regulation of macromolecule biosynthetic process (GO:0010558)

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), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), 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	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
macromolecule biosynthetic process	1
negative regulation of biosynthetic process	1
regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule 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
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
protein binding	1
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

600 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF215	BAZ2B	Q9UIF8	941
ZNF215	BAZ2A	Q9UIF9	941
ZNF215	BAZ1A	Q9NRL2	651
ZNF215	NAP1L4	Q99733	588
ZNF215	BAZ1B	Q9UIG0	582
ZNF215	DYNC1I2	Q13409	542
ZNF215	IGF2	P01344	528
ZNF215	OR2D3	Q8NGH3	501
ZNF215	NSD1	Q96L73	497
ZNF215	BRD9	Q9H8M2	480
ZNF215	TSPAN32	Q96QS1	475
ZNF215	C16orf87	Q6PH81	474
ZNF215	ZNF217	O75362	467
ZNF215	H3-3A	P06351	453
ZNF215	DUSP15	Q9H1R2	449

IntAct

15 interactions, top by confidence:

A	B	Type	Score
ZSCAN18	SCAND1	psi-mi:“MI:0914”(association)	0.740
ZNF483	ZNF197	psi-mi:“MI:0914”(association)	0.530
ZNF215	SCAND1	psi-mi:“MI:0914”(association)	0.530
ZNF215	VTA1	psi-mi:“MI:0915”(physical association)	0.400
ZNF215	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
Hacd3	ZNF215	psi-mi:“MI:0915”(physical association)	0.400
	ZNF215	psi-mi:“MI:0915”(physical association)	0.400
ZNF215		psi-mi:“MI:0915”(physical association)	0.400
ZSCAN20	ZNF197	psi-mi:“MI:0914”(association)	0.350
ZNF215	IPO8	psi-mi:“MI:0914”(association)	0.350
ZNF215	UBB	psi-mi:“MI:0914”(association)	0.350
ZSCAN1	ZNF24	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): ZNF215 (Affinity Capture-RNA), ZNF215 (Affinity Capture-MS), ZNF215 (Affinity Capture-MS), ZNF215 (Affinity Capture-RNA), HECTD1 (Affinity Capture-MS), TSEN15 (Affinity Capture-MS), TRAPPC1 (Affinity Capture-MS), ZKSCAN8 (Affinity Capture-MS), ZNF215 (Affinity Capture-MS), LRRC40 (Affinity Capture-MS), ZNF24 (Affinity Capture-MS), SCAND1 (Affinity Capture-MS), ZNF446 (Affinity Capture-MS), ZSCAN18 (Affinity Capture-MS), UBB (Affinity Capture-MS)

ESM2 similar proteins: A1KXM5, A1YFC1, A1YGK6, A2T7F2, A7KBS4, B2RXC5, E1JH25, G3X9G7, O96001, P16531, P18748, P34307, P88825, Q2EI21, Q3URU2, Q3V0C1, Q4V8E9, Q5JRM2, Q5R7U0, Q5RDG2, Q5RE50, Q5REF1, Q5SRN2, Q5SS00, Q5U4C1, Q6H236, Q6P1M9, Q6ZN11, Q810T2, Q8BUY8, Q8N3K9, Q8N660, Q8N720, Q8N859, Q8R2V3, Q920R4, Q921B4, Q923B3, Q95JY5, Q96D09

Diamond homologs: A0A1W2PQL4, A0JNB1, A0JPL0, A6NK53, A6QLU5, A6QPT6, A7MBI1, A8MT65, A8MUV8, A8MWA4, B2RXC5, B4DU55, B4DX44, E9PYI1, O14628, O75346, P0CH99, P0CI00, P17014, P17030, P17032, P17098, P51786, P85977, Q02386, Q06730, Q06732, Q0VAW7, Q12901, Q13360, Q14586, Q14588, Q14590, Q16587, Q2M3X9, Q2VY69, Q32M78, Q3ZCX4, Q49AA0, Q4R6J4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1303 predictions. Top by Δscore:

Variant	Effect	Δscore
11:6941565:CCTCA:C	acceptor_loss	1.0000
11:6941567:TCA:T	acceptor_loss	1.0000
11:6941568:CAG:C	acceptor_loss	1.0000
11:6941569:A:AC	acceptor_loss	1.0000
11:6941569:A:AG	acceptor_gain	1.0000
11:6941570:G:GG	acceptor_gain	1.0000
11:6941570:G:GT	acceptor_loss	1.0000
11:6941570:GATAT:G	acceptor_gain	1.0000
11:6941649:CACAG:C	donor_loss	1.0000
11:6941650:ACAGG:A	donor_loss	1.0000
11:6941651:CAGG:C	donor_loss	1.0000
11:6941652:AGGT:A	donor_loss	1.0000
11:6941653:GG:G	donor_loss	1.0000
11:6941654:GTG:G	donor_loss	1.0000
11:6941655:T:A	donor_loss	1.0000
11:6943170:A:T	donor_gain	1.0000
11:6926572:G:GG	donor_gain	0.9900
11:6941570:GAT:G	acceptor_gain	0.9900
11:6941644:C:T	donor_gain	0.9900
11:6943169:G:GT	donor_gain	0.9900
11:6943193:G:GT	donor_gain	0.9900
11:6943208:GC:G	donor_gain	0.9900
11:6955688:A:AG	acceptor_gain	0.9900
11:6955689:G:GG	acceptor_gain	0.9900
11:6926925:G:GT	donor_gain	0.9800
11:6941570:GATA:G	acceptor_gain	0.9800
11:6943206:T:TG	donor_gain	0.9800
11:6943210:G:GG	donor_gain	0.9800
11:6943628:G:GT	donor_gain	0.9800
11:6926569:GCA:G	donor_gain	0.9700

AlphaMissense

3479 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:6956472:T:C	F499L	0.998
11:6956474:C:A	F499L	0.998
11:6956474:C:G	F499L	0.998
11:6956139:T:C	F388L	0.997
11:6956141:C:A	F388L	0.997
11:6956141:C:G	F388L	0.997
11:6956388:T:C	F471L	0.996
11:6956390:C:A	F471L	0.996
11:6956390:C:G	F471L	0.996
11:6943116:T:C	F173L	0.995
11:6943118:C:A	F173L	0.995
11:6943118:C:G	F173L	0.995
11:6956501:T:A	H508Q	0.995
11:6956501:T:G	H508Q	0.995
11:6956407:T:C	L477P	0.994
11:6956413:G:C	R479P	0.994
11:6956417:C:A	H480Q	0.994
11:6956417:C:G	H480Q	0.994
11:6956491:T:C	L505P	0.994
11:6956168:T:A	H397Q	0.993
11:6956168:T:G	H397Q	0.993
11:6956419:A:C	Q481P	0.993
11:6956473:T:C	F499S	0.993
11:6943117:T:C	F173S	0.992
11:6956395:G:C	R473P	0.992
11:6956415:C:G	H480D	0.992
11:6956499:C:G	H508D	0.992
11:6956503:A:C	Q509P	0.991
11:6956158:T:C	L394P	0.990
11:6956180:C:A	H401Q	0.990

dbSNP variants (sampled 300 via entrez): RS1000008184 (11:6946108 A>G), RS1000012320 (11:6980716 G>A), RS1000053896 (11:6957757 T>C), RS1000061341 (11:6991170 C>T), RS1000090265 (11:6951761 C>A), RS1000211868 (11:6967012 C>G), RS1000246837 (11:6985842 T>C), RS1000255677 (11:6927388 G>A), RS1000323890 (11:6977685 T>C), RS1000385076 (11:6961294 T>C,G), RS1000406771 (11:6933768 C>T), RS1000437349 (11:6961055 T>A,C,G), RS1000442927 (11:6945665 A>G), RS1000565827 (11:6971348 G>T), RS1000633602 (11:6982291 C>T)

Disease associations

OMIM: gene MIM:605016 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Beckwith-Wiedemann syndrome	No Known Disease Relationship	Unknown

Mondo (1): Beckwith-Wiedemann syndrome (MONDO:0007534)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002345_10	Response to cytadine analogues (cytosine arabinoside)	2.000000e-06
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001506	Beckwith-Wiedemann Syndrome	C16.131.077.133; C16.131.260.080; C16.320.180.080; C16.320.447.375

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2595500	ZNF215		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression, affects methylation	3
Benzo(a)pyrene	increases expression, increases methylation	3
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	decreases methylation, affects cotreatment	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	affects cotreatment, increases methylation	1
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
CGP 52608	increases reaction, affects binding	1
ICG 001	decreases expression	1
abrine	decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Vorinostat	increases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Vehicle Emissions	decreases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00945009	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01916148	Not specified	AVAILABLE	18F-L-Fluoro-DOPA PET/CT Scan Localization of Focal Pancreatic Lesions in Subjects With Hyperinsulinemic Hypoglycemia
NCT04993235	Not specified	UNKNOWN	Body Perception and Representation in Overgrowth Syndromes, Behavioral Assessment and Neuropsychological Development
NCT05945576	Not specified	RECRUITING	IDMet (RaDiCo Cohort) (RaDiCo-IDMet)
NCT06346418	Not specified	RECRUITING	Maternal Genes and Epimutations: Beckwith-Wiedemann Syndrome & Reproductive Risks