ZNF653

Summary

ZNF653 (zinc finger protein 653, HGNC:25196) is a protein-coding gene on chromosome 19p13.2, encoding Zinc finger protein 653 (Q96CK0). Transcriptional repressor.

Enables AF-2 domain binding activity; DNA-binding transcription factor binding activity; and transcription corepressor activity. Involved in extracellular negative regulation of signal transduction and negative regulation of transcription by RNA polymerase II. Predicted to be located in extracellular region. Predicted to be active in nucleus.

Source: NCBI Gene 115950 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 86 total
• MANE Select transcript: NM_138783

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25196
Approved symbol	ZNF653
Name	zinc finger protein 653
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	Zip67
Ensembl gene	ENSG00000161914
Ensembl biotype	protein_coding
OMIM	611371
Entrez	115950

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000293771, ENST00000588541, ENST00000589051, ENST00000590296, ENST00000590548, ENST00000592756, ENST00000593191, ENST00000937056

RefSeq mRNA: 1 — MANE Select: NM_138783 NM_138783

CCDS: CCDS12261

Canonical transcript exons

ENST00000293771 — 9 exons

Exon	Start	End
ENSE00001061335	11486987	11487158
ENSE00001061344	11487292	11487903
ENSE00001248971	11505488	11505839
ENSE00003479594	11483429	11483859
ENSE00003483059	11498296	11498339
ENSE00003527610	11485656	11485770
ENSE00003528709	11486769	11486880
ENSE00003591427	11495950	11496165
ENSE00003683840	11484042	11484141

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 92.50.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6170 / max 38.9323, expressed in 343 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179246	0.6170	343

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	92.50	gold quality
cerebellar hemisphere	UBERON:0002245	92.15	gold quality
cerebellar cortex	UBERON:0002129	91.96	gold quality
cerebellum	UBERON:0002037	90.50	gold quality
left testis	UBERON:0004533	90.03	gold quality
right testis	UBERON:0004534	89.92	gold quality
testis	UBERON:0000473	86.65	gold quality
right frontal lobe	UBERON:0002810	86.53	gold quality
anterior cingulate cortex	UBERON:0009835	85.00	gold quality
lower esophagus mucosa	UBERON:0035834	84.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.11	gold quality
prefrontal cortex	UBERON:0000451	84.08	gold quality
mucosa of transverse colon	UBERON:0004991	83.86	gold quality
cortical plate	UBERON:0005343	83.82	gold quality
adenohypophysis	UBERON:0002196	82.24	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.04	gold quality
right lobe of thyroid gland	UBERON:0001119	81.87	gold quality
popliteal artery	UBERON:0002250	81.84	gold quality
tibial artery	UBERON:0007610	81.84	gold quality
left lobe of thyroid gland	UBERON:0001120	81.83	gold quality
granulocyte	CL:0000094	81.60	gold quality
hypothalamus	UBERON:0001898	80.93	gold quality
ganglionic eminence	UBERON:0004023	80.80	gold quality
body of stomach	UBERON:0001161	80.69	gold quality
caudate nucleus	UBERON:0001873	80.50	gold quality
right adrenal gland	UBERON:0001233	80.44	gold quality
neocortex	UBERON:0001950	80.44	gold quality
aorta	UBERON:0000947	80.43	gold quality
right adrenal gland cortex	UBERON:0035827	80.40	gold quality
pituitary gland	UBERON:0000007	80.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.55

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CDKN2A

miRNA regulators (miRDB)

11 targeting ZNF653, 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-4267	99.96	66.53	2368
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-3180	98.46	64.68	348
HSA-MIR-3180-3P	98.46	64.68	348
HSA-MIR-6816-5P	98.46	64.35	364
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-10396B-5P	94.99	63.57	358
HSA-MIR-1908-5P	94.99	63.41	352
HSA-MIR-663A	94.99	63.54	378
HSA-MIR-6812-3P	90.58	63.80	60

Literature-anchored findings (GeneRIF, showing 1)

• novel zinc-finger protein that influences gene activation through interaction with the functionally important activation function-2 domain of nuclear receptors (PMID:12920234)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf653	ENSDARG00000093469
mus_musculus	Zfp653	ENSMUSG00000038895
rattus_norvegicus	Zfp653	ENSRNOG00000014065

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), ZNF281 (ENSG00000162702), ZNF148 (ENSG00000163848), ZNF143 (ENSG00000166478), HIC2 (ENSG00000169635), PRDM10 (ENSG00000170325), ZNF296 (ENSG00000170684), 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 653 — Q96CK0 (reviewed: Q96CK0)

Alternative names: 67 kDa zinc finger protein, Zinc finger protein Zip67

All UniProt accessions (5): Q96CK0, K7EJG9, K7EKL4, K7EL79, K7ENS4

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor. May repress NR5A1, PPARG, NR1H3, NR4A2, ESR1 and NR3C1 transcriptional activity.

Subunit / interactions. Interacts with NR5A1.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in testis, cerebellum, temporal lobe, hippocampus and the adrenal gland. Moderately expressed in spleen, uterus, thymus, pancreas, kidney, stomach and rectum.

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

RefSeq proteins (1): NP_620138* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051061

Pfam: PF00096

UniProt features (18 total): zinc finger region 5, compositionally biased region 4, region of interest 4, short sequence motif 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CK0-F1	50.06	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 73 (showing top): TGCGCANK_UNKNOWN, E2F_Q3, GOBP_EXTRACELLULAR_REGULATION_OF_SIGNAL_TRANSDUCTION, TGAGATT_MIR216, E2F1_Q3, NRF2_01, RASHI_RESPONSE_TO_IONIZING_RADIATION_6, chr19p13, SCGGAAGY_ELK1_02, MGGAAGTG_GABP_B, GOMF_TRANSCRIPTION_FACTOR_BINDING, GOMF_TRANSCRIPTION_COREPRESSOR_ACTIVITY, ELK1_02, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, BAKKER_FOXO3_TARGETS_DN

GO Biological Process (5): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), extracellular negative regulation of signal transduction (GO:1900116), regulation of macromolecule metabolic process (GO:0060255), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (8): DNA binding (GO:0003677), transcription coregulator activity (GO:0003712), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), AF-2 domain binding (GO:0050682), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): extracellular region (GO:0005576), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
regulation of metabolic process	2
regulation of transcription by RNA polymerase II	1
regulation of DNA-templated transcription	1
extracellular region	1
negative regulation of signal transduction	1
extracellular regulation of signal transduction	1
macromolecule metabolic process	1
primary metabolic process	1
nucleic acid binding	1
transcription regulator activity	1
transcription coregulator activity	1
transition metal ion binding	1
protein domain specific binding	1
transcription factor binding	1
binding	1
cation binding	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

656 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF653	NR5A2	O00482	761
ZNF653	RNF166	Q96A37	637
ZNF653	NCOA2	Q15596	632
ZNF653	CRBN	Q96SW2	624
ZNF653	NR5A1	Q13285	593
ZNF653	NCOA1	Q15788	587
ZNF653	RAB28	P51157	570
ZNF653	DTWD1	Q8N5C7	480
ZNF653	LMBRD2	Q68DH5	475
ZNF653	GSPT1	P15170	447
ZNF653	SACK1F	Q8NEG4	445
ZNF653	DCAF6	Q58WW2	432
ZNF653	TTLL5	Q6EMB2	424
ZNF653	UBA3	Q8TBC4	406
ZNF653	NAE1	Q13564	395

IntAct

19 interactions, top by confidence:

A	B	Type	Score
CEP76	ZNF653	psi-mi:“MI:0915”(physical association)	0.560
TRIM41	ZNF653	psi-mi:“MI:0915”(physical association)	0.560
LONRF1	ZNF653	psi-mi:“MI:0915”(physical association)	0.560
MAPRE1	ZNF653	psi-mi:“MI:0915”(physical association)	0.560
ZNF653	H2BC12L	psi-mi:“MI:0915”(physical association)	0.400
ZNF653	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
ZNF653	HIST2H2BF	psi-mi:“MI:0915”(physical association)	0.400
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
ZNF653	URB1	psi-mi:“MI:0914”(association)	0.350
ZNF653	CEP76	psi-mi:“MI:0915”(physical association)	0.000
ZNF653	TRIM41	psi-mi:“MI:0915”(physical association)	0.000
LONRF1	ZNF653	psi-mi:“MI:0915”(physical association)	0.000
MAPRE1	ZNF653	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (53): ZNF653 (Two-hybrid), ZNF653 (Reconstituted Complex), ZNF653 (Two-hybrid), ZNF653 (Two-hybrid), ZNF653 (Two-hybrid), ZNF653 (Two-hybrid), ZNF653 (Proximity Label-MS), ZNF653 (Proximity Label-MS), ZNF653 (Proximity Label-MS), ZNF653 (Two-hybrid), ZNF653 (Two-hybrid), ZNF653 (Affinity Capture-RNA), THUMPD3 (Affinity Capture-MS), ZNF708 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS)

ESM2 similar proteins: A2A5K6, F1QQA8, G3V893, O08696, O14901, O57415, P36197, P37275, P97691, Q04891, Q07243, Q08050, Q14872, Q16254, Q2QGD7, Q3UH06, Q5EAC5, Q5F293, Q60542, Q62255, Q62947, Q64318, Q66K89, Q6DBW0, Q6YND2, Q7TS63, Q80X44, Q86V15, Q86VK4, Q8BG87, Q8BKX7, Q8BX22, Q8C8V1, Q8CCE9, Q8IVH2, Q91X45, Q92766, Q96CK0, Q99607, Q9BYN7

Diamond homologs: A0JC51, A2ANX9, O15391, O57311, O57415, O60481, O62836, O73689, O95409, P08048, P0C6P6, P10925, P17010, P17012, P18747, P20662, P22227, P25490, P34694, P46684, P80944, Q00899, Q10RP4, Q12145, Q15915, Q29419, Q2FAY8, Q3TTC2, Q3UH06, Q3US17, Q3Y4E1, Q52V16, Q5NVT2, Q5R782, Q5RJ54, Q61467, Q61624, Q62520, Q62521, Q62806

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1485 predictions. Top by Δscore:

Variant	Effect	Δscore
19:11483870:CCCG:C	acceptor_gain	1.0000
19:11483872:C:T	acceptor_gain	1.0000
19:11484038:TCA:T	donor_loss	1.0000
19:11484039:CAC:C	donor_loss	1.0000
19:11484040:A:AC	donor_gain	1.0000
19:11484040:ACTG:A	donor_gain	1.0000
19:11484041:C:CT	donor_gain	1.0000
19:11484041:CTG:C	donor_gain	1.0000
19:11484041:CTGC:C	donor_gain	1.0000
19:11484138:ACACC:A	acceptor_loss	1.0000
19:11484139:CAC:C	acceptor_gain	1.0000
19:11484139:CACCT:C	acceptor_loss	1.0000
19:11484140:ACCTG:A	acceptor_loss	1.0000
19:11484141:CCT:C	acceptor_loss	1.0000
19:11484143:T:A	acceptor_loss	1.0000
19:11485650:CCTGA:C	donor_loss	1.0000
19:11485651:CTGA:C	donor_loss	1.0000
19:11485651:CTGAC:C	donor_loss	1.0000
19:11485652:TGA:T	donor_loss	1.0000
19:11485652:TGAC:T	donor_loss	1.0000
19:11485653:GACCT:G	donor_loss	1.0000
19:11485654:ACC:A	donor_loss	1.0000
19:11485655:CCTG:C	donor_loss	1.0000
19:11486763:CCTCA:C	donor_loss	1.0000
19:11486764:CTCA:C	donor_loss	1.0000
19:11486765:TCA:T	donor_loss	1.0000
19:11486766:CAC:C	donor_loss	1.0000
19:11486767:ACCTG:A	donor_loss	1.0000
19:11486768:C:CT	donor_loss	1.0000
19:11486878:CTC:C	acceptor_gain	1.0000

AlphaMissense

4011 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:11483720:G:C	H604D	1.000
19:11483759:A:G	C591R	1.000
19:11483768:A:G	C588R	1.000
19:11483818:A:G	L571P	1.000
19:11483848:C:T	C561Y	1.000
19:11483849:A:G	C561R	1.000
19:11483858:A:G	C558R	1.000
19:11484062:G:C	H550Q	1.000
19:11484062:G:T	H550Q	1.000
19:11484076:G:C	H546D	1.000
19:11484076:G:T	H546N	1.000
19:11484084:A:G	L543P	1.000
19:11484101:G:C	F537L	1.000
19:11484101:G:T	F537L	1.000
19:11484102:A:G	F537S	1.000
19:11484103:A:G	F537L	1.000
19:11484114:C:T	C533Y	1.000
19:11484124:A:G	C530R	1.000
19:11484128:G:C	F528L	1.000
19:11484128:G:T	F528L	1.000
19:11484130:A:G	F528L	1.000
19:11485672:G:C	H518Q	1.000
19:11485672:G:T	H518Q	1.000
19:11485674:G:T	H518N	1.000
19:11485682:A:G	L515P	1.000
19:11485699:G:C	F509L	1.000
19:11485699:G:T	F509L	1.000
19:11485700:A:G	F509S	1.000
19:11485701:A:G	F509L	1.000
19:11485711:A:C	C505W	1.000

dbSNP variants (sampled 300 via entrez): RS1000018285 (19:11494860 G>A), RS1000046368 (19:11489207 G>A,C,T), RS1000294178 (19:11505624 ACTT>A), RS1000329578 (19:11499956 T>C), RS1000341825 (19:11494639 G>A), RS1000418373 (19:11483580 G>A,C), RS1000478759 (19:11505675 G>T), RS1000496818 (19:11504438 C>A), RS1000578949 (19:11505421 C>A,G,T), RS1000707925 (19:11485944 G>T), RS1000734544 (19:11498542 C>T), RS1000764300 (19:11498220 C>A,T), RS1000843071 (19:11489290 C>G), RS1001033010 (19:11499594 A>C), RS1001144822 (19:11489558 C>T)

Disease associations

OMIM: gene MIM:611371 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003563_11	Presence of antiphospholipid antibodies	3.000000e-06
GCST003563_12	Presence of antiphospholipid antibodies	4.000000e-06
GCST003563_6	Presence of antiphospholipid antibodies	5.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
butyraldehyde	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
pomalidomide	decreases expression, increases degradation	1
clothianidin	decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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