ZNF621

Summary

ZNF621 (zinc finger protein 621, HGNC:24787) is a protein-coding gene on chromosome 3p22.1, encoding Zinc finger protein 621 (Q6ZSS3). May be involved in transcriptional regulation.

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 regulation of transcription by RNA polymerase II. Predicted to be located in nucleus.

Source: NCBI Gene 285268 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_198484

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24787
Approved symbol	ZNF621
Name	zinc finger protein 621
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ45246
Ensembl gene	ENSG00000172888
Ensembl biotype	protein_coding
Entrez	285268

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000310898, ENST00000339296, ENST00000403205, ENST00000431278, ENST00000453351, ENST00000462161, ENST00000490457, ENST00000492098

RefSeq mRNA: 3 — MANE Select: NM_198484 NM_001098414, NM_001287245, NM_198484

CCDS: CCDS2693, CCDS74920

Canonical transcript exons

ENST00000339296 — 5 exons

Exon	Start	End
ENSE00001383038	40532030	40539782
ENSE00001524202	40524960	40525274
ENSE00003521584	40525779	40525864
ENSE00003638479	40530209	40530316
ENSE00003655752	40529319	40529445

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 88.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.4568 / max 131.4429, expressed in 1794 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36188	9.9157	1739
36187	1.2726	919
36189	1.2685	852

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	88.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.79	gold quality
medial globus pallidus	UBERON:0002477	85.70	gold quality
spinal cord	UBERON:0002240	85.50	gold quality
globus pallidus	UBERON:0001875	85.41	gold quality
corpus callosum	UBERON:0002336	85.34	gold quality
colonic epithelium	UBERON:0000397	84.13	gold quality
subthalamic nucleus	UBERON:0001906	82.52	gold quality
tendon	UBERON:0000043	82.33	gold quality
substantia nigra	UBERON:0002038	82.26	gold quality
stromal cell of endometrium	CL:0002255	82.08	gold quality
amygdala	UBERON:0001876	81.89	gold quality
lateral globus pallidus	UBERON:0002476	81.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.66	gold quality
midbrain	UBERON:0001891	81.66	gold quality
putamen	UBERON:0001874	81.49	gold quality
calcaneal tendon	UBERON:0003701	81.40	gold quality
tendon of biceps brachii	UBERON:0008188	81.35	gold quality
hypothalamus	UBERON:0001898	81.02	gold quality
ventricular zone	UBERON:0003053	80.98	gold quality
parietal pleura	UBERON:0002400	80.97	gold quality
seminal vesicle	UBERON:0000998	80.89	gold quality
visceral pleura	UBERON:0002401	80.87	gold quality
lower esophagus mucosa	UBERON:0035834	80.87	gold quality
endometrium	UBERON:0001295	80.72	gold quality
metanephros cortex	UBERON:0010533	80.67	gold quality
tibial nerve	UBERON:0001323	80.33	gold quality
sural nerve	UBERON:0015488	80.28	gold quality
inferior vagus X ganglion	UBERON:0005363	80.10	gold quality
caudate nucleus	UBERON:0001873	80.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

166 targeting ZNF621, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-4760-3P	99.93	70.50	2385

Literature-anchored findings (GeneRIF, showing 1)

• LINC01140 Regulates Radiosensitivity of Nasopharyngeal Carcinoma Cells Through the ceRNA Network. (PMID:35988287)

Cross-species orthologs

0 orthologs

Paralogs (176): ZNF195 (ENSG00000005801), ZNF112 (ENSG00000062370), ZNF275 (ENSG00000063587), ZNF37A (ENSG00000075407), ZNF510 (ENSG00000081386), ZNF506 (ENSG00000081665), ZNF268 (ENSG00000090612), MZF1 (ENSG00000099326), ZNF629 (ENSG00000102870), ZNF175 (ENSG00000105497), ZNF85 (ENSG00000105750), ZFP30 (ENSG00000120784), ZNF45 (ENSG00000124459), ZNF391 (ENSG00000124613), ZNF436 (ENSG00000125945), ZNF484 (ENSG00000127081), ZNF835 (ENSG00000127903), ZNF780B (ENSG00000128000), ZSCAN10 (ENSG00000130182), ZNF317 (ENSG00000130803), ZNF331 (ENSG00000130844), ZNF227 (ENSG00000131115), ZNF141 (ENSG00000131127), ZNF132 (ENSG00000131849), ZNF189 (ENSG00000136870), ZIM3 (ENSG00000141946), ZFP14 (ENSG00000142065), ZNF514 (ENSG00000144026), ZNF300 (ENSG00000145908), RBAK (ENSG00000146587), ZNF157 (ENSG00000147117), ZNF182 (ENSG00000147118), ZNF41 (ENSG00000147124), ZNF7 (ENSG00000147789), ZNF117 (ENSG00000152926), ZNF221 (ENSG00000159905), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631)

Protein

Protein identifiers

Zinc finger protein 621 — Q6ZSS3 (reviewed: Q6ZSS3)

All UniProt accessions (3): C9JM43, C9JZC2, Q6ZSS3

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?
Q6ZSS3-1	1	yes
Q6ZSS3-2	2

RefSeq proteins (3): NP_001091884, NP_001274174, NP_940886* (*=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 (11 total): zinc finger region 7, splice variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZSS3-F1	63.85	0.18

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 69 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, chr3p22, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, CHANDRAN_METASTASIS_UP, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_BODY, GOCC_RIBONUCLEOPROTEIN_GRANULE, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, HEIDENBLAD_AMPLICON_8Q24_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOCC_SUPRAMOLECULAR_COMPLEX, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, FOXD2_TARGET_GENES, GTF2E2_TARGET_GENES

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), developmental process (GO:0032502), 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), 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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
biological_process	1
DNA-templated transcription	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
transition metal ion binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

800 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF621	SPMIP4	Q8N865	505
ZNF621	C16orf95	Q9H693	446
ZNF621	ZNF511	Q8NB15	435
ZNF621	SMIM21	Q3B7S5	433
ZNF621	CLHC1	Q8NHS4	432
ZNF621	VRK3	Q8IV63	402
ZNF621	TSHZ3	Q63HK5	382
ZNF621	ZNG1A	Q9BRT8	364
ZNF621	KLHL35	Q6PF15	356
ZNF621	PTGR3	Q8N4Q0	351
ZNF621	OR4Q3	Q8NH05	348
ZNF621	ZSWIM4	Q9H7M6	336
ZNF621	TARBP1	Q13395	331
ZNF621	NOX4	Q9NPH5	330
ZNF621	TRUB1	Q8WWH5	317
ZNF621	OSBPL1A	Q9BXW6	317

IntAct

8 interactions, top by confidence:

A	B	Type	Score
ZNF621	LRP4	psi-mi:“MI:0914”(association)	0.530
ARSK	CANX	psi-mi:“MI:0914”(association)	0.530
ZNF621	TRIM28	psi-mi:“MI:0915”(physical association)	0.500
CCL1	ZNF621	psi-mi:“MI:0915”(physical association)	0.370
TNFSF9	ZNF621	psi-mi:“MI:0915”(physical association)	0.370
ARSK	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): TRIM28 (Affinity Capture-MS), LRP4 (Affinity Capture-MS), CBX5 (Affinity Capture-MS), TRIM39 (Affinity Capture-MS), TRIM27 (Affinity Capture-MS), TRIM39 (Affinity Capture-MS), LRP4 (Affinity Capture-MS), TRIM27 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), CBX5 (Affinity Capture-MS), TRIM39 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), ZNF621 (Affinity Capture-MS), TRIM27 (Affinity Capture-MS), CBX5 (Affinity Capture-MS)

ESM2 similar proteins: A0JPK3, A0JPL0, A2A761, A2T7D2, A3KN36, B2RU33, B2RXC5, B7ZQJ9, E1JH25, E9PYI1, G3X9G7, G5EGQ2, O43296, P08042, P17023, P18723, P18725, P18728, P18733, P18748, P18752, Q0VCB0, Q14592, Q29RZ4, Q2TL60, Q5MYW4, Q5PPG4, Q5R7I8, Q5RBY9, Q62396, Q6PF04, Q6ZN11, Q6ZSS3, Q7Z398, Q8BIQ3, Q8BQC8, Q8IZ26, Q8N988, Q8N9Z0, Q8T053

Diamond homologs: A1L1L7, A3KN32, A3KN36, A6NFI3, A6NM28, A6NN14, A6QLU5, A7MBI1, A8K8V0, A8MTY0, A8MWA4, B4DU55, C9JBD0, G3X9G7, O60765, O75290, O94892, O95780, P0C7X2, P10072, P15622, P16373, P16374, P17023, P17032, P17097, P17098, P21506, P52742, P59923, Q06730, Q08DG8, Q16587, Q29RZ4, Q2TL60, Q3V080, Q49AA0, Q4R6C2, Q4V8A8, Q5FWF6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1047 predictions. Top by Δscore:

Variant	Effect	Δscore
3:40525861:TCAGG:T	donor_loss	1.0000
3:40525862:CAGGT:C	donor_loss	1.0000
3:40525863:AGGT:A	donor_loss	1.0000
3:40525864:GGTG:G	donor_loss	1.0000
3:40525865:G:A	donor_loss	1.0000
3:40525866:T:G	donor_loss	1.0000
3:40530203:A:AG	acceptor_gain	1.0000
3:40530203:AT:A	acceptor_gain	1.0000
3:40530204:T:G	acceptor_gain	1.0000
3:40530204:T:TA	acceptor_gain	1.0000
3:40530207:A:AG	acceptor_gain	1.0000
3:40530208:G:GG	acceptor_gain	1.0000
3:40530208:GTA:G	acceptor_gain	1.0000
3:40530208:GTAGC:G	acceptor_gain	1.0000
3:40525777:A:AG	acceptor_gain	0.9900
3:40525778:G:GG	acceptor_gain	0.9900
3:40530208:GT:G	acceptor_gain	0.9900
3:40530211:GC:G	acceptor_gain	0.9900
3:40525774:CTTA:C	acceptor_loss	0.9800
3:40525775:TTA:T	acceptor_loss	0.9800
3:40525776:TAG:T	acceptor_gain	0.9800
3:40525777:A:C	acceptor_loss	0.9800
3:40525778:GCT:G	acceptor_gain	0.9800
3:40529442:CTGGG:C	donor_loss	0.9800
3:40529443:TGGG:T	donor_loss	0.9800
3:40529445:GGTA:G	donor_loss	0.9800
3:40529446:GTAAG:G	donor_loss	0.9800
3:40529447:T:TC	donor_loss	0.9800
3:40530210:A:AG	acceptor_gain	0.9800
3:40530211:G:GG	acceptor_gain	0.9800

AlphaMissense

2875 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:40532500:T:C	F244L	0.995
3:40532502:C:A	F244L	0.995
3:40532502:C:G	F244L	0.995
3:40532752:T:C	F328L	0.995
3:40532754:C:A	F328L	0.995
3:40532754:C:G	F328L	0.995
3:40532668:T:C	F300L	0.994
3:40532670:C:A	F300L	0.994
3:40532670:C:G	F300L	0.994
3:40532584:T:C	F272L	0.993
3:40532586:C:A	F272L	0.993
3:40532586:C:G	F272L	0.993
3:40532615:A:C	Q282P	0.991
3:40532332:T:C	F188L	0.990
3:40532334:C:A	F188L	0.990
3:40532334:C:G	F188L	0.990
3:40532625:T:A	H285Q	0.988
3:40532625:T:G	H285Q	0.988
3:40532753:T:C	F328S	0.987
3:40532457:C:A	H229Q	0.986
3:40532457:C:G	H229Q	0.986
3:40532527:C:G	H253D	0.986
3:40532695:C:G	H309D	0.986
3:40532697:T:A	H309Q	0.986
3:40532697:T:G	H309Q	0.986
3:40532529:T:A	H253Q	0.985
3:40532529:T:G	H253Q	0.985
3:40532611:C:G	H281D	0.985
3:40532248:T:C	F160L	0.983
3:40532250:C:A	F160L	0.983

dbSNP variants (sampled 300 via entrez): RS1000094609 (3:40539779 A>G), RS1000172178 (3:40530122 T>C,G), RS1000205060 (3:40529863 T>G), RS1000500391 (3:40531723 C>T), RS1000530914 (3:40531487 C>G), RS1000665316 (3:40522980 C>G), RS1000699355 (3:40523312 G>C), RS1000771066 (3:40536702 A>G,T), RS1000839863 (3:40536665 T>C), RS1001045177 (3:40525382 T>C), RS1001172070 (3:40528653 G>A), RS1001512575 (3:40539809 A>G), RS1001717377 (3:40522675 C>T), RS1001998738 (3:40531219 A>G), RS1002063409 (3:40532838 C>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

3 associations (top):

Study	Trait	p-value
GCST005232_29	Neuroticism	2.000000e-08
GCST006143_2	Bone mineral density (total hip)	4.000000e-07
GCST010002_421	Refractive error	3.000000e-27

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0007702	hip bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, affects expression, affects cotreatment	5
Air Pollutants	affects expression, increases expression, affects methylation, increases abundance	3
sodium arsenite	increases abundance, increases expression	2
Tunicamycin	increases expression	2
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Arsenic	increases abundance, increases expression	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Nitrogen Dioxide	affects methylation, increases abundance	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XW67	HEK293 eGFP-ZNF621	Transformed cell line	Female

Clinical trials (associated diseases)

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