ZNF296

Summary

ZNF296 (zinc finger protein 296, HGNC:15981) is a protein-coding gene on chromosome 19q13.32, encoding Zinc finger protein 296 (Q8WUU4). May be a transcriptional corepressor with KLF4.

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of dendrite development; regulation of transcription by RNA polymerase II; and spermatogenesis. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 162979 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_145288

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15981
Approved symbol	ZNF296
Name	zinc finger protein 296
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170684
Ensembl biotype	protein_coding
OMIM	613226
Entrez	162979

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000303809

RefSeq mRNA: 1 — MANE Select: NM_145288 NM_145288

CCDS: CCDS12653

Canonical transcript exons

ENST00000303809 — 3 exons

Exon	Start	End
ENSE00001159053	45075713	45075862
ENSE00001159062	45071500	45072580
ENSE00001159072	45076076	45076478

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 87.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6485 / max 159.3972, expressed in 1219 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181440	11.9188	1180
181441	0.4354	212
181439	0.2942	167

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	87.38	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.75	gold quality
granulocyte	CL:0000094	83.49	gold quality
nasal cavity epithelium	UBERON:0005384	82.63	silver quality
lower esophagus mucosa	UBERON:0035834	80.80	gold quality
leukocyte	CL:0000738	80.19	gold quality
monocyte	CL:0000576	80.15	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	78.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.92	gold quality
vastus lateralis	UBERON:0001379	78.45	gold quality
mucosa of transverse colon	UBERON:0004991	78.36	gold quality
quadriceps femoris	UBERON:0001377	77.13	gold quality
esophagus mucosa	UBERON:0002469	76.11	gold quality
myocardium	UBERON:0002349	74.36	gold quality
blood	UBERON:0000178	74.30	gold quality
skin of abdomen	UBERON:0001416	72.72	gold quality
parotid gland	UBERON:0001831	72.71	silver quality
kidney epithelium	UBERON:0004819	72.58	gold quality
spleen	UBERON:0002106	72.51	gold quality
bone marrow cell	CL:0002092	72.33	silver quality
right hemisphere of cerebellum	UBERON:0014890	72.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.13	gold quality
epithelial cell of pancreas	CL:0000083	72.09	gold quality
cerebellar cortex	UBERON:0002129	72.04	gold quality
cerebellar hemisphere	UBERON:0002245	71.98	gold quality
skin of leg	UBERON:0001511	71.88	gold quality
cerebellum	UBERON:0002037	71.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	71.21	gold quality
zone of skin	UBERON:0000014	70.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.75

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
LEFTY1
MPO

miRNA regulators (miRDB)

9 targeting ZNF296, 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-7845-5P	99.88	64.88	771
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-432-5P	98.00	68.13	989
HSA-MIR-890	97.47	68.67	982
HSA-MIR-885-3P	95.14	63.08	448
HSA-MIR-6753-5P	94.70	64.08	470

Literature-anchored findings (GeneRIF, showing 1)

• novel translocation t(17;19)(q22;q13.32)in acute myeloid leukemia mapping to 352 bp 5 of MPO on 17q & 2,085 bp 5 of ZNF342 on 19q on derivative chromosome 17; higher level of ZNF342 expression in acute lymphoblastic leukemia associated with poorer outcome (PMID:19255975)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf296	ENSDARG00000077897
mus_musculus	Zfp296	ENSMUSG00000011267
rattus_norvegicus	Zfp296	ENSRNOG00000049605

Paralogs (36): ZBTB32 (ENSG00000011590), SNAI2 (ENSG00000019549), PRDM1 (ENSG00000057657), PRDM6 (ENSG00000061455), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZNF451 (ENSG00000112200), ZBTB45 (ENSG00000119574), ZNF410 (ENSG00000119725), SNAI1 (ENSG00000124216), ZNF384 (ENSG00000126746), ZBTB1 (ENSG00000126804), VEZF1 (ENSG00000136451), PRDM14 (ENSG00000147596), ZNF276 (ENSG00000158805), ZNF362 (ENSG00000160094), ZNF653 (ENSG00000161914), ZNF281 (ENSG00000162702), ZNF148 (ENSG00000163848), ZNF143 (ENSG00000166478), HIC2 (ENSG00000169635), PRDM10 (ENSG00000170325), ZNF692 (ENSG00000171163), ZNF575 (ENSG00000176472), HIC1 (ENSG00000177374), ZBTB18 (ENSG00000179456), ZBTB42 (ENSG00000179627), ZBTB20 (ENSG00000181722), ZBTB7C (ENSG00000184828), SNAI3 (ENSG00000185669), ZFP91 (ENSG00000186660), MTF1 (ENSG00000188786), SCRT2 (ENSG00000215397), SCRT1 (ENSG00000261678)

Protein

Protein identifiers

Zinc finger protein 296 — Q8WUU4 (reviewed: Q8WUU4)

Alternative names: Zinc finger protein 342

All UniProt accessions (1): Q8WUU4

UniProt curated annotations — full annotation on UniProt →

Function. May be a transcriptional corepressor with KLF4.

Subunit / interactions. Interacts with KLF4.

Subcellular location. Nucleus.

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

RefSeq proteins (1): NP_660331* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051497	Dev/Hematopoietic_TF	Family
IPR057448	BCL-11A_Znf_CCHC	Domain

Pfam: PF00096, PF25491

UniProt features (14 total): zinc finger region 6, compositionally biased region 4, region of interest 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUU4-F1	58.47	0.04

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 (1): 35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 119 (showing top): GOBP_DENDRITE_DEVELOPMENT, RORA1_01, ROVERSI_GLIOMA_COPY_NUMBER_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, AREB6_01, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GOBP_MALE_GAMETE_GENERATION, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_DENDRITE_DEVELOPMENT, IRF1_Q6

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), spermatogenesis (GO:0007283), negative regulation of dendrite development (GO:2000171)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515), 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
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
developmental process involved in reproduction	1
male gamete generation	1
negative regulation of neuron projection development	1
dendrite development	1
regulation of dendrite development	1
negative regulation of developmental process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

658 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF296	MPO	P05164	763
ZNF296	KLF4	P78338	643
ZNF296	UTF1	Q5T230	573
ZNF296	NR0B1	P51843	561
ZNF296	ERAS	Q7Z444	543
ZNF296	GDF3	Q9NR23	501
ZNF296	CES1	P23141	493
ZNF296	TRIM25	Q14258	425
ZNF296	CCDC59	Q9P031	406
ZNF296	NANOG	Q9H9S0	403
ZNF296	LEUTX	A8MZ59	396
ZNF296	CRIPTO	P13385	391
ZNF296	PWWP2A	Q96N64	386
ZNF296	ESRRB	O95718	358
ZNF296	SOX2	P48431	352

IntAct

51 interactions, top by confidence:

A	B	Type	Score
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
L3MBTL2	E2F6	psi-mi:“MI:0914”(association)	0.730
CRYAA	ZNF296	psi-mi:“MI:0915”(physical association)	0.560
ZNF296		psi-mi:“MI:0915”(physical association)	0.560
ZNF296	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
FKBP1A	ZNF296	psi-mi:“MI:0915”(physical association)	0.560
GRN	ZNF296	psi-mi:“MI:0915”(physical association)	0.560
HSPA2	ZNF296	psi-mi:“MI:0915”(physical association)	0.560
ZNF296	PRPS1	psi-mi:“MI:0915”(physical association)	0.560
ZNF296	GIPC1	psi-mi:“MI:0915”(physical association)	0.560
ZNF296	TOR1AIP1	psi-mi:“MI:0915”(physical association)	0.560
ZNF296	RNF11	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	ZNF296	psi-mi:“MI:0915”(physical association)	0.560
SNCA	ZNF296	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (37): ZNF296 (Affinity Capture-MS), ZNF296 (Affinity Capture-MS), ZNF296 (Affinity Capture-MS), ZNF296 (Affinity Capture-MS), ZNF296 (Affinity Capture-MS), ZNF296 (Affinity Capture-MS), ZNF296 (Proximity Label-MS), LIN52 (Affinity Capture-MS), PWWP2A (Affinity Capture-MS), BCL11A (Affinity Capture-MS), ZNF296 (Affinity Capture-MS), SAP30 (Affinity Capture-MS), ZNF296 (Affinity Capture-MS), LIN9 (Affinity Capture-MS), HJURP (Affinity Capture-MS)

ESM2 similar proteins: A0JNJ4, A2APT9, A6NEL2, A6NP61, B1ASB6, B1WBS3, B2RXF5, F6WEQ6, O15015, O43918, O88282, O88286, O95785, P98168, P98169, Q2M3G4, Q2MHN3, Q2QGD7, Q3U1J1, Q3U381, Q497V6, Q5SW24, Q5SXM2, Q6YND2, Q6ZMQ8, Q6ZMY3, Q7TN08, Q7TSX9, Q80SU3, Q80YE4, Q811H0, Q8BG26, Q8BZW2, Q8C8V1, Q8IX07, Q8IY92, Q8N143, Q8N1G0, Q8NC74, Q8TBE0

Diamond homologs: A1L2U9, A2A884, A2ANX9, A7Y7X5, B0X9H6, B0YDH7, B1WAZ8, B1WBU4, O35615, O62836, O77459, P08048, P10925, P15822, P17010, P17012, P20662, P31505, P31629, P60319, P78871, P80944, Q00900, Q01611, Q02031, Q03172, Q0IH98, Q0VCJ6, Q292R5, Q29419, Q3UHF7, Q52V16, Q5JPB2, Q5T1R4, Q6B4Z5, Q7JM44, Q811F1, Q86UZ6, Q8BID6, Q8CII0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
NuRD complex assembly	6	38.5×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

188 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45072576:TCGTT:T	acceptor_gain	1.0000
19:45072577:CGTT:C	acceptor_gain	1.0000
19:45072577:CGTTC:C	acceptor_gain	1.0000
19:45072578:GTT:G	acceptor_gain	1.0000
19:45072578:GTTC:G	acceptor_loss	1.0000
19:45072579:TT:T	acceptor_gain	1.0000
19:45072579:TTCT:T	acceptor_loss	1.0000
19:45072581:C:CC	acceptor_gain	1.0000
19:45072581:C:CG	acceptor_loss	1.0000
19:45072582:T:A	acceptor_loss	1.0000
19:45072584:G:C	acceptor_gain	1.0000
19:45072584:G:GC	acceptor_gain	1.0000
19:45075711:A:AC	donor_gain	1.0000
19:45075711:AC:A	donor_gain	1.0000
19:45075711:ACC:A	donor_loss	1.0000
19:45075712:C:CC	donor_gain	1.0000
19:45075712:CC:C	donor_gain	1.0000
19:45075712:CCT:C	donor_gain	1.0000
19:45075712:CCTG:C	donor_gain	1.0000
19:45075859:CGGT:C	acceptor_gain	1.0000
19:45075860:GGT:G	acceptor_gain	1.0000
19:45075861:GT:G	acceptor_gain	1.0000
19:45075862:TCT:T	acceptor_loss	1.0000
19:45075863:C:CC	acceptor_gain	1.0000
19:45075863:CTGCA:C	acceptor_loss	1.0000
19:45075708:CTCA:C	donor_gain	0.9900
19:45075712:CCTGA:C	donor_gain	0.9900
19:45075858:GCGGT:G	acceptor_gain	0.9900
19:45075859:CGGTC:C	acceptor_gain	0.9900
19:45075861:GTCT:G	acceptor_gain	0.9900

AlphaMissense

3088 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45071667:G:C	F454L	1.000
19:45071667:G:T	F454L	1.000
19:45071669:A:G	F454L	1.000
19:45071690:A:G	C447R	1.000
19:45071733:G:C	H432Q	1.000
19:45071733:G:T	H432Q	1.000
19:45071735:G:C	H432D	1.000
19:45071735:G:T	H432N	1.000
19:45071737:C:G	R431P	1.000
19:45071738:G:T	R431S	1.000
19:45071805:G:C	H408Q	1.000
19:45071805:G:T	H408Q	1.000
19:45071807:G:C	H408D	1.000
19:45071813:G:T	R406S	1.000
19:45071819:G:C	H404D	1.000
19:45071819:G:T	H404N	1.000
19:45071844:A:C	F395L	1.000
19:45071844:A:T	F395L	1.000
19:45071845:A:G	F395S	1.000
19:45071846:A:G	F395L	1.000
19:45071640:G:C	H463Q	0.999
19:45071640:G:T	H463Q	0.999
19:45071642:G:C	H463D	0.999
19:45071668:A:G	F454S	0.999
19:45071689:C:G	C447S	0.999
19:45071690:A:T	C447S	0.999
19:45071731:C:G	R433P	0.999
19:45071734:T:C	H432R	0.999
19:45071743:A:G	L429P	0.999
19:45071747:T:C	K428E	0.999

dbSNP variants (sampled 300 via entrez): RS1000032922 (19:45073654 G>A), RS1000141476 (19:45077508 G>T), RS1000186948 (19:45072770 A>C), RS1000654308 (19:45073152 A>G), RS1000657357 (19:45078132 A>C,G), RS1001430582 (19:45074869 G>A,C), RS1001540621 (19:45078370 G>A,C), RS1001821385 (19:45072831 A>G), RS1002427386 (19:45074101 G>A), RS1002475825 (19:45076584 C>G), RS1003256883 (19:45077352 C>T), RS1004161299 (19:45073894 C>T), RS1004380811 (19:45073707 G>A), RS1004421239 (19:45073009 C>T), RS1005841496 (19:45072509 G>A)

Disease associations

OMIM: gene MIM:613226 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST007827_13	Alzheimer’s disease or HDL levels (pleiotropy)	7.000000e-22
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-97
GCST007827_5	Alzheimer’s disease or HDL levels (pleiotropy)	7.000000e-74
GCST007827_8	Alzheimer’s disease or HDL levels (pleiotropy)	3.000000e-36

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
sodium arsenate	increases abundance, increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	increases expression, affects cotreatment	1
pentanal	increases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases 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, increases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases expression	1
Formaldehyde	increases expression	1
Niclosamide	increases expression	1

Clinical trials (associated diseases)

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