ZNF599

Summary

ZNF599 (zinc finger protein 599, HGNC:26408) is a protein-coding gene on chromosome 19q13.11, encoding Zinc finger protein 599 (Q96NL3). 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 148103 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 101 total
• MANE Select transcript: NM_001007248

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26408
Approved symbol	ZNF599
Name	zinc finger protein 599
Location	19q13.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30663
Ensembl gene	ENSG00000153896
Ensembl biotype	protein_coding
Entrez	148103

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000329285, ENST00000587354, ENST00000588760, ENST00000588788, ENST00000673678, ENST00000673783

RefSeq mRNA: 1 — MANE Select: NM_001007248 NM_001007248

CCDS: CCDS32991

Canonical transcript exons

ENST00000329285 — 4 exons

Exon	Start	End
ENSE00001383883	34767316	34767411
ENSE00001419749	34758073	34760559
ENSE00002917037	34772824	34773215
ENSE00003502965	34769429	34769555

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 87.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.8784 / max 37.9892, expressed in 1576 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180452	4.3700	1558
208777	0.5084	263

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	87.87	gold quality
right uterine tube	UBERON:0001302	85.51	gold quality
oviduct epithelium	UBERON:0004804	82.51	gold quality
left testis	UBERON:0004533	81.66	gold quality
right testis	UBERON:0004534	81.48	gold quality
left lobe of thyroid gland	UBERON:0001120	80.76	gold quality
right lobe of thyroid gland	UBERON:0001119	80.49	gold quality
testis	UBERON:0000473	80.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.88	gold quality
thyroid gland	UBERON:0002046	79.81	gold quality
adenohypophysis	UBERON:0002196	79.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.17	gold quality
pituitary gland	UBERON:0000007	78.80	gold quality
body of uterus	UBERON:0009853	78.54	gold quality
cortical plate	UBERON:0005343	78.10	gold quality
endocervix	UBERON:0000458	77.99	gold quality
metanephros cortex	UBERON:0010533	77.80	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.73	gold quality
left ovary	UBERON:0002119	77.62	gold quality
right ovary	UBERON:0002118	77.48	gold quality
fallopian tube	UBERON:0003889	77.22	gold quality
stromal cell of endometrium	CL:0002255	77.08	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.04	gold quality
lower esophagus	UBERON:0013473	77.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.00	gold quality
apex of heart	UBERON:0002098	76.94	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	76.92	gold quality
right adrenal gland	UBERON:0001233	76.89	gold quality
right adrenal gland cortex	UBERON:0035827	76.87	gold quality
muscle layer of sigmoid colon	UBERON:0035805	76.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

56 targeting ZNF599, 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-340-5P	100.00	72.50	4437
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-6088	99.29	68.45	1284

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), ZNF19 (ENSG00000157429), ZNF589 (ENSG00000164048), PRDM9 (ENSG00000164256), ZNF180 (ENSG00000167384), ZNF558 (ENSG00000167785), ZNF35 (ENSG00000169981), ZNF778 (ENSG00000170100), ZNF439 (ENSG00000171291), ZNF440 (ENSG00000171295), ZNF556 (ENSG00000172000), ZNF554 (ENSG00000172006), ZNF596 (ENSG00000172748), 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 599 — Q96NL3 (reviewed: Q96NL3)

All UniProt accessions (3): Q96NL3, A0A669KB57, K7EJP3

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?
Q96NL3-1	1	yes
Q96NL3-2	2

RefSeq proteins (1): NP_001007249* (*=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

Pfam: PF00096, PF01352

UniProt features (20 total): zinc finger region 14, splice variant 2, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NL3-F1	73.59	0.31

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 35 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, BASAKI_YBX1_TARGETS_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, DODD_NASOPHARYNGEAL_CARCINOMA_DN, CHEMNITZ_RESPONSE_TO_PROSTAGLANDIN_E2_DN, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, KUMAR_AUTOPHAGY_NETWORK, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, CEBPZ_TARGET_GENES, OVOL3_TARGET_GENES, ZNF350_TARGET_GENES, ZNF407_TARGET_GENES, MIR5688, MIR340_5P

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

288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF599	SCGB2B2	Q4G0G5	507
ZNF599	SPMIP7	A4D263	407
ZNF599	RWDD4	Q6NW29	405
ZNF599	TASOR2	Q5VWN6	395
ZNF599	POGZ	Q7Z3K3	387
ZNF599	EFCAB13	Q8IY85	383
ZNF599	ZBTB21	Q9ULJ3	375
ZNF599	UBA2	Q9UBT2	365
ZNF599	PHF8	Q9UPP1	364
ZNF599	ZNF385B	Q569K4	355
ZNF599	TTK	P33981	352
ZNF599	LSM14A	Q8ND56	349
ZNF599	WTIP	A6NIX2	348
ZNF599	ZDHHC8	Q9ULC8	326
ZNF599	MBOAT1	Q6ZNC8	297

IntAct

129 interactions, top by confidence:

A	B	Type	Score
ZNF599	NDEL1	psi-mi:“MI:0915”(physical association)	0.720
NDEL1	ZNF599	psi-mi:“MI:0915”(physical association)	0.720
ZNF599	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
TSGA10	ZNF599	psi-mi:“MI:0915”(physical association)	0.560
CEP70	ZNF599	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	ZNF599	psi-mi:“MI:0915”(physical association)	0.560
	ZNF599	psi-mi:“MI:0915”(physical association)	0.560
ZNF599	ZRANB1	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	ZNF599	psi-mi:“MI:0915”(physical association)	0.560
ZNF599	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF599	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF599	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF599	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI3	ZNF599	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF599	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF599	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF599	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF599	GOPC	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF599	TJP2	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF599	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF599	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (10): ZNF599 (Two-hybrid), ZNF599 (Two-hybrid), ZNF599 (Two-hybrid), ZNF599 (Two-hybrid), ZNF599 (Two-hybrid), ZNF599 (Two-hybrid), ZNF599 (Two-hybrid), NDEL1 (Two-hybrid), GOLGA6L9 (Two-hybrid), KRTAP10-9 (Two-hybrid)

ESM2 similar proteins: A0JNB1, A1YF12, A1YG88, A2T759, A3KN32, B2RUI1, O43296, O75123, P10072, P17020, P17097, P51814, P52736, P52740, Q07230, Q08ER8, Q13398, Q14590, Q32KN0, Q3KQV3, Q3MIS6, Q4V8A8, Q5CZA5, Q5RBQ3, Q5RBX0, Q5RCD9, Q5RCX4, Q6GQR8, Q6NX45, Q6P9A3, Q6PK81, Q7TSH9, Q7TSI0, Q7Z7L9, Q86UD4, Q8BFS8, Q8BLB0, Q8IVP9, Q8IZ26, Q8N9F8

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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
Ras activation upon Ca2+ influx through NMDA receptor	5	51.0×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	48.5×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	48.5×	2e-06
Assembly and cell surface presentation of NMDA receptors	10	45.3×	1e-12
Dopamine Neurotransmitter Release Cycle	5	44.3×	2e-06
Long-term potentiation	5	42.5×	3e-06
Neurexins and neuroligins	11	38.7×	6e-13
Protein-protein interactions at synapses	7	33.2×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	76.5×	2e-14
protein localization to synapse	6	60.5×	9e-08
receptor clustering	7	57.5×	6e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	6	39.1×	1e-06
cell-cell adhesion	9	12.0×	4e-06
protein-containing complex assembly	8	12.0×	2e-05
chemical synaptic transmission	7	7.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

598 predictions. Top by Δscore:

Variant	Effect	Δscore
19:34769423:TCTTA:T	donor_loss	1.0000
19:34769424:CTTAC:C	donor_loss	1.0000
19:34769425:TTAC:T	donor_loss	1.0000
19:34769426:TACCC:T	donor_loss	1.0000
19:34769427:AC:A	donor_gain	1.0000
19:34769428:CC:C	donor_gain	1.0000
19:34767411:CCTG:C	acceptor_gain	0.9900
19:34769422:GTCTT:G	donor_loss	0.9900
19:34769427:A:AC	donor_gain	0.9900
19:34769428:C:CC	donor_gain	0.9900
19:34769461:A:AC	donor_gain	0.9900
19:34769467:T:TA	donor_gain	0.9900
19:34769551:AATGC:A	acceptor_gain	0.9900
19:34769553:TGC:T	acceptor_gain	0.9900
19:34769556:C:CA	acceptor_loss	0.9900
19:34769556:C:CC	acceptor_gain	0.9900
19:34769557:T:C	acceptor_loss	0.9900
19:34771317:A:AC	donor_gain	0.9900
19:34772816:CCACT:C	donor_loss	0.9900
19:34772817:CACTC:C	donor_loss	0.9900
19:34772818:ACTCA:A	donor_loss	0.9900
19:34772819:CTCA:C	donor_loss	0.9900
19:34772820:TCAC:T	donor_loss	0.9900
19:34772821:CA:C	donor_loss	0.9900
19:34772823:C:A	donor_loss	0.9900
19:34760573:A:T	acceptor_gain	0.9800
19:34767311:CCAA:C	donor_loss	0.9800
19:34767312:CAAC:C	donor_loss	0.9800
19:34767313:AAC:A	donor_loss	0.9800
19:34767314:ACC:A	donor_loss	0.9800

AlphaMissense

3914 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:34759169:G:C	F544L	0.997
19:34759169:G:T	F544L	0.997
19:34759171:A:G	F544L	0.997
19:34759253:A:C	F516L	0.997
19:34759253:A:T	F516L	0.997
19:34759255:A:G	F516L	0.997
19:34759421:A:C	F460L	0.997
19:34759421:A:T	F460L	0.997
19:34759423:A:G	F460L	0.997
19:34759589:A:C	F404L	0.997
19:34759589:A:T	F404L	0.997
19:34759591:A:G	F404L	0.997
19:34759398:C:G	R468P	0.996
19:34759505:A:C	F432L	0.996
19:34759505:A:T	F432L	0.996
19:34759507:A:G	F432L	0.996
19:34759925:G:C	F292L	0.996
19:34759925:G:T	F292L	0.996
19:34759927:A:G	F292L	0.996
19:34759230:C:G	R524P	0.995
19:34759314:C:G	R496P	0.995
19:34759566:C:G	R412P	0.995
19:34759337:A:C	F488L	0.994
19:34759337:A:T	F488L	0.994
19:34759339:A:G	F488L	0.994
19:34759478:A:C	H441Q	0.993
19:34759478:A:T	H441Q	0.993
19:34759142:G:C	H553Q	0.992
19:34759142:G:T	H553Q	0.992
19:34759310:G:C	H497Q	0.992

dbSNP variants (sampled 300 via entrez): RS1000084033 (19:34788842 G>A,T), RS1000124083 (19:34784304 C>G,T), RS1000312005 (19:34795387 G>A), RS1000355057 (19:34774404 C>T), RS1000359046 (19:34795146 A>G), RS1000508215 (19:34770082 T>C,G), RS1000554140 (19:34793402 G>A), RS1000578688 (19:34768893 C>T), RS1000613845 (19:34761729 G>A), RS1000617571 (19:34775795 T>A), RS1000648350 (19:34762166 C>G), RS1000653035 (19:34807289 C>G,T), RS1000691300 (19:34776232 A>G), RS1000722248 (19:34808447 G>C,T), RS1000782873 (19:34775052 T>G)

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

4 associations (top):

Study	Trait	p-value
GCST002827_6	Urate levels (BMI interaction)	9.000000e-07
GCST003427_56	Alzheimer disease and age of onset	4.000000e-07
GCST006256_1	Long-term memory (delayed word recall task)	7.000000e-06
GCST006993_14	Hippocampal volume in Alzheimer’s disease dementia	6.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0004847	age at onset
EFO:0006805	word list delayed recall measurement
EFO:0005035	hippocampal volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, increases expression	3
Nickel	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cannabidiol	decreases expression	1
Smoke	increases abundance, increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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