ZNF496

Summary

ZNF496 (zinc finger protein 496, HGNC:23713) is a protein-coding gene on chromosome 1q44, encoding Zinc finger protein 496 (Q96IT1). DNA-binding transcription factor that can both act as an activator and a repressor.

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 positive regulation of DNA-templated transcription and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus.

Source: NCBI Gene 84838 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 99 total — 1 pathogenic
• MANE Select transcript: NM_032752

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23713
Approved symbol	ZNF496
Name	zinc finger protein 496
Location	1q44
Locus type	gene with protein product
Status	Approved
Aliases	ZKSCAN17, MGC15548, ZSCAN49
Ensembl gene	ENSG00000162714
Ensembl biotype	protein_coding
OMIM	613911
Entrez	84838

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000294753, ENST00000461277, ENST00000462139, ENST00000477903, ENST00000478225, ENST00000682384, ENST00000907816, ENST00000907817, ENST00000907818, ENST00000907819, ENST00000931781, ENST00000931782, ENST00000931783, ENST00000931784, ENST00000931785, ENST00000931786, ENST00000957628

RefSeq mRNA: 2 — MANE Select: NM_032752 NM_001329733, NM_032752

CCDS: CCDS1631

Canonical transcript exons

ENST00000682384 — 10 exons

Exon	Start	End
ENSE00001125272	247329966	247330081
ENSE00001867480	247331432	247331647
ENSE00003238039	247308475	247308588
ENSE00003261522	247323154	247323230
ENSE00003336724	247328683	247328866
ENSE00003358268	247310324	247310456
ENSE00003370585	247309699	247309806
ENSE00003581283	247329189	247329615
ENSE00003919105	247297415	247301276
ENSE00003920002	247331790	247331867

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 89.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9979 / max 87.0869, expressed in 1735 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18506	9.9979	1735

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	89.99	gold quality
ganglionic eminence	UBERON:0004023	89.39	gold quality
cortical plate	UBERON:0005343	88.82	gold quality
body of uterus	UBERON:0009853	88.13	gold quality
tibialis anterior	UBERON:0001385	88.04	silver quality
ventricular zone	UBERON:0003053	87.90	gold quality
left ovary	UBERON:0002119	87.17	gold quality
right uterine tube	UBERON:0001302	86.59	gold quality
gastrocnemius	UBERON:0001388	86.55	gold quality
endocervix	UBERON:0000458	86.43	gold quality
body of pancreas	UBERON:0001150	86.38	gold quality
muscle of leg	UBERON:0001383	86.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.81	gold quality
tendon of biceps brachii	UBERON:0008188	85.78	gold quality
stromal cell of endometrium	CL:0002255	85.54	gold quality
left uterine tube	UBERON:0001303	85.54	gold quality
ovary	UBERON:0000992	85.47	gold quality
right ovary	UBERON:0002118	85.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.78	gold quality
cartilage tissue	UBERON:0002418	84.60	gold quality
mucosa of stomach	UBERON:0001199	84.46	gold quality
pancreas	UBERON:0001264	84.33	gold quality
right coronary artery	UBERON:0001625	84.26	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.25	gold quality
tibial artery	UBERON:0007610	84.09	gold quality
popliteal artery	UBERON:0002250	84.08	gold quality
ectocervix	UBERON:0012249	83.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.76	gold quality
lower esophagus	UBERON:0013473	83.71	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	83.61	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.38
E-MTAB-6379	no	113.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting ZNF496, 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-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-4701-5P	96.45	68.41	1121
HSA-MIR-588	96.45	68.36	1127

Literature-anchored findings (GeneRIF, showing 1)

• the Nizp1 KRAB-domain was identified to possess an intrinsic transcriptional activation capacity suppressed in cis by the presence of the C2HR domain (PMID:20176155)

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	Zkscan17	ENSMUSG00000020472
rattus_norvegicus	Zfp496	ENSRNOG00000003129
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), ZKSCAN2 (ENSG00000155592), 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 496 — Q96IT1 (reviewed: Q96IT1)

Alternative names: Zinc finger protein with KRAB and SCAN domains 17

All UniProt accessions (2): A0A0C4DGR5, Q96IT1

UniProt curated annotations — full annotation on UniProt →

Function. DNA-binding transcription factor that can both act as an activator and a repressor.

Subunit / interactions. Interacts (via zinc-fingers) with JARID2. Interacts with NSD1.

Subcellular location. Nucleus.

Domain organisation. The C2H2-type zinc finger 1, also named C2HR, mediates the interaction with NSD1.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q96IT1-1	1	yes
Q96IT1-2	2

RefSeq proteins (2): NP_001316662, NP_116141* (*=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

Pfam: PF00096, PF01352, PF02023

UniProt features (20 total): zinc finger region 5, region of interest 4, cross-link 3, domain 2, compositionally biased region 2, modified residue 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96IT1-F1	55.02	0.02

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 (5): 185, 299, 13, 403, 496

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 76 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, MAZ_Q6, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, chr1q44, ETF_Q6, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, CHENG_IMPRINTED_BY_ESTRADIOL, BILANGES_RAPAMYCIN_SENSITIVE_VIA_TSC1_AND_TSC2, TORCHIA_TARGETS_OF_EWSR1_FLI1_FUSION_DN, KRIEG_HYPOXIA_NOT_VIA_KDM3A, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GSE14415_NATURAL_TREG_VS_TCONV_UP, GSE10240_CTRL_VS_IL17_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_UP, LMTK3_TARGET_GENES, PBXIP1_TARGET_GENES

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA-templated transcription (GO:0045893), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): 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 (GO:0003677), zinc ion binding (GO:0008270), protein binding (GO:0005515), 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
DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
positive regulation of RNA biosynthetic process	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
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

822 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF496	NSD1	Q96L73	671
ZNF496	OR2B11	Q5JQS5	559
ZNF496	ZC2HC1B	Q5TFG8	439
ZNF496	PDCL3	Q9H2J4	412
ZNF496	SPATA25	Q9BR10	371
ZNF496	RBM46	Q8TBY0	326
ZNF496	RNFT1	Q5M7Z0	325
ZNF496	PPP1R2C	O14990	324
ZNF496	CT47A11	Q5JQC4	324
ZNF496	SPANXN1	Q5VSR9	323
ZNF496	OR2V2	Q96R30	315
ZNF496	BUB3	O43684	312
ZNF496	RASGEF1C	Q8N431	311
ZNF496	NAP1L3	Q99457	309
ZNF496	C1orf174	Q8IYL3	306

IntAct

124 interactions, top by confidence:

A	B	Type	Score
PGBD1	ZNF24	psi-mi:“MI:0914”(association)	0.900
ZKSCAN4	ZNF496	psi-mi:“MI:0915”(physical association)	0.850
ZNF496	ZKSCAN4	psi-mi:“MI:0915”(physical association)	0.850
ZSCAN22	ZNF496	psi-mi:“MI:0915”(physical association)	0.780
ZNF496	ZNF446	psi-mi:“MI:0915”(physical association)	0.780
ZNF496	ZSCAN22	psi-mi:“MI:0915”(physical association)	0.780
ZNF446	ZNF496	psi-mi:“MI:0915”(physical association)	0.780
PGBD1	ZNF496	psi-mi:“MI:0915”(physical association)	0.780
ZNF496	PGBD1	psi-mi:“MI:0915”(physical association)	0.780
ZNF496	ARR3	psi-mi:“MI:0915”(physical association)	0.770
ARR3	ZNF496	psi-mi:“MI:0915”(physical association)	0.770
ZNF496	ZSCAN21	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (88): ZNF496 (Two-hybrid), ZNF496 (Two-hybrid), ZNF496 (Two-hybrid), ZNF496 (Two-hybrid), ZNF483 (Two-hybrid), ZSCAN22 (Two-hybrid), ZKSCAN4 (Two-hybrid), ZNF496 (Reconstituted Complex), ZNF496 (Affinity Capture-MS), ZNF496 (Affinity Capture-MS), ZNF496 (Affinity Capture-MS), ZNF496 (Affinity Capture-MS), ZNF496 (Affinity Capture-MS), ZNF496 (Two-hybrid), ZNF496 (Two-hybrid)

ESM2 similar proteins: A0A1D5NS60, A0JN76, A1YFX5, A2T7G6, A6NJL1, D2HQI1, F1MJR8, O14901, P0CG00, P10754, P22227, P98182, Q0IJ29, Q1L8W0, Q3SWU4, Q5DW34, Q5EAC5, Q5EXX3, Q5RHB5, Q5SXI5, Q5T619, Q66H04, Q6NRM8, Q6NV66, Q6ZSB9, Q7M6U3, Q7TS63, Q7TSH3, Q7ZWZ4, Q801P1, Q86VK4, Q8BKX7, Q8BXX2, Q8NAM6, Q8NAP3, Q8NCP5, Q8R0A2, Q91VW9, Q96IT1, Q96N77

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	83
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3906954	NM_032752.3(ZNF496):c.1530dup (p.Glu511fs)	Pathogenic

SpliceAI

2469 predictions. Top by Δscore:

Variant	Effect	Δscore
1:247308594:C:CT	acceptor_gain	1.0000
1:247308594:C:T	acceptor_gain	1.0000
1:247308595:A:T	acceptor_gain	1.0000
1:247309695:TCA:T	donor_loss	1.0000
1:247309696:CACCC:C	donor_loss	1.0000
1:247309697:A:AC	donor_gain	1.0000
1:247309697:AC:A	donor_gain	1.0000
1:247309697:ACC:A	donor_gain	1.0000
1:247309698:C:CC	donor_gain	1.0000
1:247309698:CC:C	donor_gain	1.0000
1:247309698:CCC:C	donor_gain	1.0000
1:247309698:CCCA:C	donor_gain	1.0000
1:247309698:CCCAA:C	donor_gain	1.0000
1:247309802:GTCGT:G	acceptor_gain	1.0000
1:247309803:TCGT:T	acceptor_gain	1.0000
1:247309804:CGT:C	acceptor_gain	1.0000
1:247309804:CGTC:C	acceptor_gain	1.0000
1:247309805:GT:G	acceptor_gain	1.0000
1:247309806:TC:T	acceptor_loss	1.0000
1:247309807:C:A	acceptor_loss	1.0000
1:247309807:C:CC	acceptor_gain	1.0000
1:247309808:T:A	acceptor_loss	1.0000
1:247309812:C:CT	acceptor_gain	1.0000
1:247310322:A:AC	donor_gain	1.0000
1:247310323:C:CC	donor_gain	1.0000
1:247328867:C:CC	acceptor_gain	1.0000
1:247329184:CTCA:C	donor_loss	1.0000
1:247329185:TCA:T	donor_loss	1.0000
1:247329186:CA:C	donor_loss	1.0000
1:247329187:A:AC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000066348 (1:247329795 G>C), RS1000069200 (1:247327912 C>A,T), RS1000087149 (1:247330431 C>T), RS1000145828 (1:247311263 G>A), RS1000325762 (1:247318465 AG>A), RS1000562964 (1:247309954 C>A), RS1000566976 (1:247303829 G>A), RS1000626397 (1:247311716 T>A), RS1000654826 (1:247307280 T>C), RS1000663736 (1:247320003 A>G), RS1000775133 (1:247298107 T>C), RS1000904653 (1:247314352 T>C), RS1000933620 (1:247309713 T>C), RS1001048617 (1:247316513 C>G), RS1001079411 (1:247316790 G>A)

Disease associations

OMIM: gene MIM:613911 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002929_1	Chromium levels	1.000000e-06
GCST90002401_410	Platelet distribution width	3.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, increases methylation	2
Smoke	decreases expression, decreases reaction	2
TAK-243	increases sumoylation	1
arsenite	increases methylation	1
Decitabine	decreases expression, decreases reaction	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	decreases expression	1
Coumestrol	decreases expression	1
Valproic Acid	decreases expression	1
Cyclosporine	increases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A8I3	SEES3-1V human ZNF496, clone1	Embryonic stem cell	Male
CVCL_A8I4	SEES3-1V human ZNF496, clone2	Embryonic stem cell	Male
CVCL_A8I5	SEES3-1V human ZNF496, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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