ZNF596

Summary

ZNF596 (zinc finger protein 596, HGNC:27268) is a protein-coding gene on chromosome 8p23.3, encoding Zinc finger protein 596 (Q8TC21). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 169270 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 116 total
• MANE Select transcript: NM_001042416

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27268
Approved symbol	ZNF596
Name	zinc finger protein 596
Location	8p23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172748
Ensembl biotype	protein_coding
Entrez	169270

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 17 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000308811, ENST00000320552, ENST00000398612, ENST00000518320, ENST00000518414, ENST00000521145, ENST00000521238, ENST00000521270, ENST00000522866, ENST00000523162, ENST00000523333, ENST00000523418, ENST00000640035, ENST00000872805, ENST00000872806, ENST00000872807, ENST00000872808, ENST00000872809, ENST00000949223, ENST00000949224, ENST00000949225

RefSeq mRNA: 7 — MANE Select: NM_001042416 NM_001042415, NM_001042416, NM_001287254, NM_001287255, NM_001287256, NM_001287399, NM_173539

CCDS: CCDS5951

Canonical transcript exons

ENST00000398612 — 6 exons

Exon	Start	End
ENSE00001533903	232456	232694
ENSE00003704827	242887	243013
ENSE00003704980	240824	240907
ENSE00003707150	243722	243805
ENSE00003708664	244619	244701
ENSE00003843727	245154	247339

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 85.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.8338 / max 54.2742, expressed in 1463 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87132	2.5578	1239
87131	1.2759	792

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	85.97	gold quality
cerebellar hemisphere	UBERON:0002245	85.52	gold quality
cerebellar cortex	UBERON:0002129	85.33	gold quality
sural nerve	UBERON:0015488	84.20	gold quality
mucosa of stomach	UBERON:0001199	83.81	gold quality
cerebellum	UBERON:0002037	83.30	gold quality
calcaneal tendon	UBERON:0003701	83.25	gold quality
metanephros cortex	UBERON:0010533	81.77	gold quality
right uterine tube	UBERON:0001302	81.63	gold quality
left ovary	UBERON:0002119	81.49	gold quality
tibial nerve	UBERON:0001323	81.42	gold quality
body of uterus	UBERON:0009853	80.90	gold quality
right testis	UBERON:0004534	80.78	gold quality
left testis	UBERON:0004533	80.77	gold quality
right lobe of thyroid gland	UBERON:0001119	80.53	gold quality
left lobe of thyroid gland	UBERON:0001120	80.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.00	gold quality
adenohypophysis	UBERON:0002196	79.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.61	gold quality
right ovary	UBERON:0002118	79.43	gold quality
testis	UBERON:0000473	79.32	gold quality
endocervix	UBERON:0000458	79.14	gold quality
thyroid gland	UBERON:0002046	79.00	gold quality
ectocervix	UBERON:0012249	78.64	gold quality
popliteal artery	UBERON:0002250	78.58	gold quality
tibial artery	UBERON:0007610	78.58	gold quality
pituitary gland	UBERON:0000007	78.36	gold quality
right adrenal gland	UBERON:0001233	78.25	gold quality
left adrenal gland	UBERON:0001234	78.02	gold quality
body of pancreas	UBERON:0001150	77.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.46

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2496.1	ZNF596	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605368

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

50 targeting ZNF596, 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-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-935	98.82	69.36	1072

Literature-anchored findings (GeneRIF, showing 1)

• a genome-wide search of association between European ancestry and Multiple sclerosis (MS) revealed a region of interest close to the ZNF596 gene on chromosome 8 in Hispanics; cases had a significantly higher proportion of European ancestry compared to controls. (PMID:30653506)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	CG2712	FBGN0024975
drosophila_melanogaster	Phs	FBGN0036522
drosophila_melanogaster	CG3281	FBGN0260741

Paralogs (62): ZNF582 (ENSG00000018869), ZNF264 (ENSG00000083844), ZNF343 (ENSG00000088876), ZNF684 (ENSG00000117010), ZNF133 (ENSG00000125846), ZNF557 (ENSG00000130544), ZNF337 (ENSG00000130684), ZNF20 (ENSG00000132010), ZFP37 (ENSG00000136866), ZNF614 (ENSG00000142556), KRBOX4 (ENSG00000147121), ZNF599 (ENSG00000153896), ZNF19 (ENSG00000157429), ZNF589 (ENSG00000164048), PRDM9 (ENSG00000164256), ZNF180 (ENSG00000167384), ZNF558 (ENSG00000167785), ZNF35 (ENSG00000169981), ZNF778 (ENSG00000170100), ZNF439 (ENSG00000171291), ZNF440 (ENSG00000171295), ZNF556 (ENSG00000172000), ZNF554 (ENSG00000172006), ZNF80 (ENSG00000174255), ZNF266 (ENSG00000174652), ZNF25 (ENSG00000175395), ZNF77 (ENSG00000175691), ZNF169 (ENSG00000175787), ZNF404 (ENSG00000176222), ZNF491 (ENSG00000177599), ZNF620 (ENSG00000177842), ZNF619 (ENSG00000177873), ZNF875 (ENSG00000181666), ZNF329 (ENSG00000181894), ZFP90 (ENSG00000184939), ZNF566 (ENSG00000186017), ZNF529 (ENSG00000186020), ZNF749 (ENSG00000186230), ZNF555 (ENSG00000186300), ZNF70 (ENSG00000187792)

Protein

Protein identifiers

Zinc finger protein 596 — Q8TC21 (reviewed: Q8TC21)

All UniProt accessions (8): Q8TC21, A0A1W2PNU1, E5RHT8, E5RIL8, E5RIV8, E5RJH7, V9GYI9, V9GYV6

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 (3)

UniProt ID	Names	Canonical?
Q8TC21-1	1	yes
Q8TC21-2	2
Q8TC21-3	3

RefSeq proteins (7): NP_001035880, NP_001035881, NP_001274183, NP_001274184, NP_001274185, NP_001274328, NP_775810 (=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

UniProt features (20 total): zinc finger region 11, splice variant 4, sequence variant 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TC21-F1	70.34	0.32

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 44 (showing top): GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ALKBH3_TARGET_GENES, CBX5_TARGET_GENES, DIDO1_TARGET_GENES, OVOL3_TARGET_GENES, PHF21A_TARGET_GENES, RLF_TARGET_GENES, TOP2B_TARGET_GENES, ZFP91_TARGET_GENES, ZNF362_TARGET_GENES, ZNF561_TARGET_GENES, ZNF664_TARGET_GENES, MIR205_3P, MIR6873_3P

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

GO Molecular Function (6): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), zinc ion binding (GO:0008270), DNA binding (GO:0003677), 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	1
transcription by RNA polymerase II	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription cis-regulatory region binding	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

486 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF596	TDRP	Q86YL5	645
ZNF596	ERICH1	Q86X53	594
ZNF596	FBXO25	Q8TCJ0	583
ZNF596	KBTBD11	O94819	474
ZNF596	OR4F21	O95013	472
ZNF596	BTG4	Q9NY30	468
ZNF596	ZAR1L	A6NP61	431
ZNF596	CST9	Q5W186	410
ZNF596	ARHGEF10	O15013	399
ZNF596	REC114	Q7Z4M0	393
ZNF596	DLGAP2	Q9P1A6	386
ZNF596	HFM1	A2PYH4	372
ZNF596	TIGD6	Q17RP2	370
ZNF596	LITAF	Q99732	366
ZNF596	MLH3	P49751	353

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PSMA6	ZNF596	psi-mi:“MI:0915”(physical association)	0.560
STAT5A	ZNF596	psi-mi:“MI:0915”(physical association)	0.370
PSMA6	ZNF596	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): ZNF596 (Two-hybrid), ZNF596 (Affinity Capture-RNA), ZNF596 (Proximity Label-MS), ZNF596 (Proximity Label-MS), ZNF596 (Proximity Label-MS), ZNF596 (Proximity Label-MS), ZNF596 (Proximity Label-MS), ZNF596 (Proximity Label-MS), ZNF596 (Two-hybrid)

ESM2 similar proteins: A2RRD8, A6NHJ4, B4DX44, O75346, P10077, P10755, P15621, P16372, P16373, P51786, P52737, P85977, Q0VGE8, Q14588, Q147U1, Q15928, Q15973, Q2M3X9, Q3KNS6, Q3MIS6, Q494X3, Q5HY98, Q5RBQ3, Q5REK1, Q5VIY5, Q60585, Q61751, Q6GQR8, Q7L2R6, Q7TSH9, Q8IYX0, Q8N782, Q8N823, Q8N988, Q8N9F8, Q8NA42, Q8NCK3, Q8NDP4, Q8NEP9, Q8TC21

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	105
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

839 predictions. Top by Δscore:

Variant	Effect	Δscore
8:243009:TATTG:T	donor_gain	1.0000
8:243011:TTG:T	donor_gain	1.0000
8:243013:GGTG:G	donor_loss	1.0000
8:243014:G:GG	donor_gain	1.0000
8:244608:A:AG	acceptor_gain	1.0000
8:244609:T:G	acceptor_gain	1.0000
8:244612:A:AG	acceptor_gain	1.0000
8:244615:TCA:T	acceptor_loss	1.0000
8:244616:CA:C	acceptor_loss	1.0000
8:244617:A:AG	acceptor_gain	1.0000
8:244617:AGGT:A	acceptor_loss	1.0000
8:244618:G:GG	acceptor_gain	1.0000
8:244618:GGT:G	acceptor_gain	1.0000
8:244618:GGTA:G	acceptor_gain	1.0000
8:244699:ATGG:A	donor_loss	1.0000
8:244700:TGGTA:T	donor_loss	1.0000
8:244701:GGTA:G	donor_loss	1.0000
8:244702:G:C	donor_loss	1.0000
8:244702:G:GG	donor_gain	1.0000
8:244703:T:A	donor_loss	1.0000
8:245146:A:AG	acceptor_gain	1.0000
8:245147:A:G	acceptor_gain	1.0000
8:240823:GATTT:G	acceptor_gain	0.9900
8:242885:AG:A	acceptor_gain	0.9900
8:242886:GG:G	acceptor_gain	0.9900
8:243010:ATTG:A	donor_gain	0.9900
8:243012:TG:T	donor_gain	0.9900
8:243013:GG:G	donor_gain	0.9900
8:243016:GAGTC:G	donor_loss	0.9900
8:245152:A:AG	acceptor_gain	0.9900

AlphaMissense

3372 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:245541:T:C	F232L	0.999
8:245543:T:A	F232L	0.999
8:245543:T:G	F232L	0.999
8:245877:T:C	F344L	0.999
8:245879:C:A	F344L	0.999
8:245879:C:G	F344L	0.999
8:246129:T:C	F428L	0.999
8:246131:C:A	F428L	0.999
8:246131:C:G	F428L	0.999
8:245625:T:C	F260L	0.998
8:245627:C:A	F260L	0.998
8:245627:C:G	F260L	0.998
8:245709:T:C	F288L	0.998
8:245711:C:A	F288L	0.998
8:245711:C:G	F288L	0.998
8:246045:T:C	F400L	0.998
8:246047:C:A	F400L	0.998
8:246047:C:G	F400L	0.998
8:246064:T:C	L406P	0.998
8:245793:T:C	F316L	0.997
8:245795:C:A	F316L	0.997
8:245795:C:G	F316L	0.997
8:245961:T:C	F372L	0.997
8:245963:C:A	F372L	0.997
8:245963:C:G	F372L	0.997
8:246070:G:C	R408P	0.997
8:246213:T:C	F456L	0.997
8:246215:C:A	F456L	0.997
8:246215:C:G	F456L	0.997
8:246297:T:C	F484L	0.997

dbSNP variants (sampled 300 via entrez): RS1000156163 (8:240290 A>G,T), RS1000199500 (8:237526 C>G), RS1000252952 (8:240700 C>G,T), RS1000271515 (8:240076 G>C), RS1000331276 (8:232152 A>G), RS1000674259 (8:244726 G>A,T), RS1001107804 (8:244575 C>A), RS1001534906 (8:244845 C>A), RS1001692570 (8:236085 T>C,G), RS1001762054 (8:239592 A>T), RS1001764784 (8:240398 G>A), RS1002266726 (8:237264 T>G), RS1002680182 (8:236505 G>A,C,T), RS1002736583 (8:246984 T>A,C), RS1002905514 (8:230938 C>A,T)

Disease associations

OMIM: gene `` | 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

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, affects methylation	3
Valproic Acid	decreases expression, increases methylation	2
Magnetite Nanoparticles	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
zinc chromate	increases abundance, increases expression	1
ferrous chloride	increases expression	1
resorcinol	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Succimer	increases expression, affects cotreatment	1
Formaldehyde	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cyclosporine	increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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