ZNF461

Summary

ZNF461 (zinc finger protein 461, HGNC:21629) is a protein-coding gene on chromosome 19q13.13, encoding Zinc finger protein 461 (Q8TAF7). 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 active in nucleus.

Source: NCBI Gene 92283 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_153257

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21629
Approved symbol	ZNF461
Name	zinc finger protein 461
Location	19q13.13
Locus type	gene with protein product
Status	Approved
Aliases	GIOT-1, MGC33911
Ensembl gene	ENSG00000197808
Ensembl biotype	protein_coding
OMIM	608640
Entrez	92283

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 4 protein_coding, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000360357, ENST00000396893, ENST00000540605, ENST00000588268, ENST00000588844, ENST00000589442, ENST00000590361, ENST00000590487, ENST00000591370, ENST00000591827, ENST00000592496, ENST00000592829

RefSeq mRNA: 8 — MANE Select: NM_153257 NM_001297623, NM_001322821, NM_001322823, NM_001322825, NM_001322826, NM_001322827, NM_001322828, NM_153257

CCDS: CCDS54257, CCDS74348

Canonical transcript exons

ENST00000588268 — 6 exons

Exon	Start	End
ENSE00001526631	36666690	36666837
ENSE00002913857	36636618	36640043
ENSE00003506703	36664698	36664786
ENSE00003593322	36658299	36658425
ENSE00003675166	36643794	36643862
ENSE00003787713	36656448	36656543

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 84.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.4126 / max 132.9588, expressed in 1550 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180688	5.4126	1550

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	84.08	gold quality
cerebellar hemisphere	UBERON:0002245	82.19	gold quality
cerebellar cortex	UBERON:0002129	82.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.68	gold quality
ventricular zone	UBERON:0003053	81.49	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.48	gold quality
islet of Langerhans	UBERON:0000006	81.10	gold quality
adrenal tissue	UBERON:0018303	80.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.32	gold quality
ganglionic eminence	UBERON:0004023	80.11	gold quality
cerebellum	UBERON:0002037	79.78	gold quality
calcaneal tendon	UBERON:0003701	79.70	gold quality
colonic epithelium	UBERON:0000397	78.90	gold quality
anterior cingulate cortex	UBERON:0009835	78.16	gold quality
prefrontal cortex	UBERON:0000451	78.06	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.04	gold quality
monocyte	CL:0000576	77.88	gold quality
popliteal artery	UBERON:0002250	77.65	gold quality
tibial artery	UBERON:0007610	77.65	gold quality
leukocyte	CL:0000738	77.62	gold quality
right frontal lobe	UBERON:0002810	77.32	gold quality
mucosa of stomach	UBERON:0001199	77.24	gold quality
left adrenal gland	UBERON:0001234	77.23	gold quality
right adrenal gland	UBERON:0001233	77.18	gold quality
left adrenal gland cortex	UBERON:0035825	77.17	gold quality
sural nerve	UBERON:0015488	77.07	gold quality
bone marrow cell	CL:0002092	77.02	gold quality
right adrenal gland cortex	UBERON:0035827	77.01	gold quality
stromal cell of endometrium	CL:0002255	77.00	gold quality
smooth muscle tissue	UBERON:0001135	76.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.70

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CYP19A1	Repression
NR5A2	Repression
SF1

Upstream regulators (CollecTRI, top): CREB1, NR0B1, NR4A1, NR5A1

miRNA regulators (miRDB)

67 targeting ZNF461, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
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-433-3P	99.98	69.37	1203
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909

Literature-anchored findings (GeneRIF, showing 1)

• Molecular cloning and tissue distribution of ZNF461. (PMID:15004467)

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 461 — Q8TAF7 (reviewed: Q8TAF7)

Alternative names: Gonadotropin-inducible ovary transcription repressor 1

All UniProt accessions (7): B4DRP8, Q8TAF7, K7EIW1, K7EJM1, K7EKL0, K7ESQ5, X6RBI5

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed, with highest levels in liver, kidney, pancreas, thymus, and small intestine.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TAF7-1	1	yes
Q8TAF7-2	2

RefSeq proteins (8): NP_001284552, NP_001309750, NP_001309752, NP_001309754, NP_001309755, NP_001309756, NP_001309757, NP_694989* (*=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
IPR050752	C2H2-ZF_domain	Family

Pfam: PF00096, PF01352

UniProt features (16 total): zinc finger region 12, chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAF7-F1	65.14	0.10

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 68 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, NIKOLSKY_MUTATED_AND_AMPLIFIED_IN_BREAST_CANCER, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ALKBH3_TARGET_GENES, DIDO1_TARGET_GENES, GLI4_TARGET_GENES, RYBP_TARGET_GENES, ZIM3_TARGET_GENES, ZNF274_TARGET_GENES, ZNF30_TARGET_GENES, ZNF329_TARGET_GENES, ZNF350_TARGET_GENES, ZNF502_TARGET_GENES

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 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
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

476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF461	TOX2	Q96NM4	923
ZNF461	PHGDH	O43175	687
ZNF461	LIME1	Q9H400	602
ZNF461	SLA2	Q9H6Q3	601
ZNF461	LGALS4	P56470	505
ZNF461	DEFB4A	O15263	466
ZNF461	DEPDC4	Q8N2C3	418
ZNF461	CEP57L1	Q8IYX8	378
ZNF461	CCDC61	Q9Y6R9	369
ZNF461	HEATR4	Q86WZ0	357
ZNF461	MSH3	P20585	353
ZNF461	EPHB2	P29323	352
ZNF461	MSH6	P52701	351
ZNF461	PGCKA1	Q8IY42	348
ZNF461	JRKL	Q9Y4A0	312

IntAct

8 interactions, top by confidence:

A	B	Type	Score
	ZNF461	psi-mi:“MI:0915”(physical association)	0.560
ZNF461	MDFI	psi-mi:“MI:0915”(physical association)	0.560
NDEL1	ZNF461	psi-mi:“MI:0915”(physical association)	0.000
MDFI	ZNF461	psi-mi:“MI:0915”(physical association)	0.000
ZNF461	MDFI	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): KRTAP10-3 (Two-hybrid), ZNF461 (Affinity Capture-RNA), ZNF461 (Synthetic Lethality), ZNF461 (Two-hybrid), ZNF461 (Affinity Capture-MS), ZNF461 (Affinity Capture-MS), SF1 (Reconstituted Complex), ZNF461 (Reconstituted Complex), HDAC2 (Reconstituted Complex)

ESM2 similar proteins: A0A087WUV0, A0JNB1, A2VDP4, B2RUI1, P0CG31, P10072, P17025, P17036, P17097, P18733, P51814, Q08ER8, Q09FC8, Q0VGE8, Q14590, Q15937, Q16600, Q2M3X9, Q4V8A8, Q5CZA5, Q5R8G9, Q5RBX0, Q5VIY5, Q68DI1, Q6J6I6, Q6NX49, Q6P1L6, Q6PG37, Q6ZMS4, Q6ZMW2, Q80YP6, Q86UD4, Q86Y25, Q8IZ26, Q8N184, Q8NB42, Q8NEK5, Q8TAF7, Q8TF47, Q8WXB4

Diamond homologs: A0A1W2PQL4, A6NK75, A6NN14, A6NNF4, A6NP11, A8MQ14, A8MTY0, A8MUV8, A8MXY4, B4DX44, B4DXR9, E9PYI1, O14628, O43345, O75290, O75346, O75373, O75437, O95780, P0CB33, P0DKX0, P0DPD5, P16373, P17019, P17038, P21506, P35789, P52736, P52738, P52744, Q03923, Q03924, Q03936, Q03938, Q05481, Q14586, Q14593, Q14929, Q15928, Q3KNS6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

925 predictions. Top by Δscore:

Variant	Effect	Δscore
19:36658337:T:TA	donor_gain	1.0000
19:36664787:C:CC	acceptor_gain	0.9900
19:36664803:T:C	acceptor_gain	0.9900
19:36664803:T:TC	acceptor_gain	0.9900
19:36666684:TCTTA:T	donor_loss	0.9900
19:36666685:CTTA:C	donor_loss	0.9900
19:36666686:TTA:T	donor_loss	0.9900
19:36666687:TA:T	donor_loss	0.9900
19:36666689:C:CT	donor_loss	0.9900
19:36656528:T:C	acceptor_gain	0.9800
19:36664696:A:AC	donor_gain	0.9800
19:36664697:C:CC	donor_gain	0.9800
19:36664784:TTG:T	acceptor_gain	0.9800
19:36666689:CCTT:C	donor_gain	0.9800
19:36640039:CAAGT:C	acceptor_gain	0.9700
19:36640043:TCTGA:T	acceptor_loss	0.9700
19:36640044:C:CC	acceptor_gain	0.9700
19:36640044:C:G	acceptor_loss	0.9700
19:36640045:T:G	acceptor_loss	0.9700
19:36643788:TTATA:T	donor_loss	0.9700
19:36643789:TATA:T	donor_loss	0.9700
19:36643790:ATAC:A	donor_loss	0.9700
19:36643791:TACC:T	donor_loss	0.9700
19:36643792:A:AT	donor_loss	0.9700
19:36643793:C:G	donor_loss	0.9700
19:36643794:C:G	donor_loss	0.9700
19:36664785:TG:T	acceptor_gain	0.9700
19:36666688:A:AC	donor_gain	0.9700
19:36666689:C:CC	donor_gain	0.9700
19:36640041:AGT:A	acceptor_gain	0.9600

AlphaMissense

3787 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:36639163:A:C	F394L	0.998
19:36639163:A:T	F394L	0.998
19:36639165:A:G	F394L	0.998
19:36639247:A:C	F366L	0.997
19:36639247:A:T	F366L	0.997
19:36639249:A:G	F366L	0.997
19:36638827:A:C	F506L	0.996
19:36638827:A:T	F506L	0.996
19:36638829:A:G	F506L	0.996
19:36638911:A:C	F478L	0.996
19:36638911:A:T	F478L	0.996
19:36638913:A:G	F478L	0.996
19:36638995:A:C	F450L	0.996
19:36638995:A:T	F450L	0.996
19:36638997:A:G	F450L	0.996
19:36639415:A:C	F310L	0.996
19:36639415:A:T	F310L	0.996
19:36639417:A:G	F310L	0.996
19:36639331:A:C	F338L	0.995
19:36639331:A:T	F338L	0.995
19:36639333:A:G	F338L	0.995
19:36639079:A:C	F422L	0.994
19:36639079:A:T	F422L	0.994
19:36639081:A:G	F422L	0.994
19:36639230:A:G	L372P	0.994
19:36638884:A:C	H487Q	0.993
19:36638884:A:T	H487Q	0.993
19:36638966:T:G	Q460P	0.993
19:36638882:T:G	Q488P	0.992
19:36639218:T:G	Q376P	0.992

dbSNP variants (sampled 300 via entrez): RS1000128174 (19:36658633 C>A,T), RS1000169302 (19:36647624 T>G), RS1000238237 (19:36650713 A>G), RS1000317511 (19:36643973 C>T), RS1000389340 (19:36655277 T>C), RS1000441906 (19:36655655 C>T), RS1000521944 (19:36636588 G>A), RS1000626169 (19:36648137 C>T), RS1000668552 (19:36653609 G>A,C), RS1000693327 (19:36651187 C>T), RS1000942246 (19:36664619 A>G), RS1001091083 (19:36657007 C>T), RS1001112354 (19:36667292 CG>C), RS1001123516 (19:36667598 A>C), RS1001125197 (19:36656742 G>A)

Disease associations

OMIM: gene MIM:608640 | 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

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	increases expression	1
triphenyl phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	decreases expression	1
cupric oxide	increases expression	1
cylindrospermopsin	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Colforsin	decreases reaction, increases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Tobacco Smoke Pollution	increases expression	1
Triiodothyronine	decreases expression	1
Urethane	increases expression	1
Copper Sulfate	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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