ZNF875

Summary

ZNF875 (zinc finger protein 875, HGNC:4928) is a protein-coding gene on chromosome 19q13.12, encoding Zinc finger protein 875 (P10072). 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 284459 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 115 total
• MANE Select transcript: NM_001353803

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4928
Approved symbol	ZNF875
Name	zinc finger protein 875
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000181666
Ensembl biotype	protein_coding
OMIM	165250
Entrez	284459

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 28 protein_coding, 5 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000324411, ENST00000392153, ENST00000541583, ENST00000544914, ENST00000585623, ENST00000586897, ENST00000587437, ENST00000587570, ENST00000587829, ENST00000588820, ENST00000589188, ENST00000589218, ENST00000589392, ENST00000589801, ENST00000590166, ENST00000590386, ENST00000590570, ENST00000590582, ENST00000591134, ENST00000591259, ENST00000591391, ENST00000591417, ENST00000591471, ENST00000591485, ENST00000592168, ENST00000592362, ENST00000592768, ENST00000652615, ENST00000862310, ENST00000862311, ENST00000862312, ENST00000862313, ENST00000862314, ENST00000862315, ENST00000911520, ENST00000970697, ENST00000970698

RefSeq mRNA: 22 — MANE Select: NM_001353803 NM_001329761, NM_001329762, NM_001329763, NM_001329764, NM_001329765, NM_001329766, NM_001329767, NM_001329768, NM_001329769, NM_001329770, NM_001329771, NM_001329772, NM_001329773, NM_001329774, NM_001329775, NM_001329776, NM_001329777, NM_001329778, NM_001329779, NM_001353803, NM_001353804, NM_181786

CCDS: CCDS12502, CCDS82337, CCDS82338, CCDS82339, CCDS86758

Canonical transcript exons

ENST00000392153 — 5 exons

Exon	Start	End
ENSE00001664741	37334649	37334782
ENSE00002816417	37362109	37364447
ENSE00003526968	37347190	37347316
ENSE00003643497	37335169	37335257
ENSE00003659035	37347777	37347872

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 98.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.9051 / max 252.0935, expressed in 1745 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175545	12.8719	1704
175547	6.7378	1582
175548	0.1178	60
175546	0.1165	44
175551	0.0552	6
175550	0.0059	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	98.45	gold quality
endothelial cell	CL:0000115	96.41	gold quality
right uterine tube	UBERON:0001302	95.68	gold quality
right lobe of thyroid gland	UBERON:0001119	95.54	gold quality
left lobe of thyroid gland	UBERON:0001120	95.31	gold quality
cerebellar hemisphere	UBERON:0002245	95.19	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.19	gold quality
adenohypophysis	UBERON:0002196	95.11	gold quality
cerebellar cortex	UBERON:0002129	95.10	gold quality
thyroid gland	UBERON:0002046	94.86	gold quality
pituitary gland	UBERON:0000007	94.60	gold quality
apex of heart	UBERON:0002098	94.42	gold quality
right adrenal gland cortex	UBERON:0035827	94.36	gold quality
right adrenal gland	UBERON:0001233	94.00	gold quality
cerebellum	UBERON:0002037	93.95	gold quality
left adrenal gland cortex	UBERON:0035825	93.74	gold quality
left adrenal gland	UBERON:0001234	93.47	gold quality
left ovary	UBERON:0002119	93.47	gold quality
right ovary	UBERON:0002118	93.22	gold quality
metanephros cortex	UBERON:0010533	92.94	gold quality
minor salivary gland	UBERON:0001830	92.80	gold quality
primary visual cortex	UBERON:0002436	92.73	gold quality
right testis	UBERON:0004534	92.65	gold quality
left testis	UBERON:0004533	92.61	gold quality
adrenal gland	UBERON:0002369	92.54	gold quality
adrenal cortex	UBERON:0001235	92.52	gold quality
endocervix	UBERON:0000458	92.28	gold quality
body of uterus	UBERON:0009853	92.26	gold quality
right atrium auricular region	UBERON:0006631	92.16	gold quality
skin of abdomen	UBERON:0001416	92.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

40 targeting ZNF875, 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-9-5P	100.00	72.28	2361
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-3136-5P	98.53	67.68	793
HSA-MIR-4439	98.53	67.53	793
HSA-MIR-6883-3P	97.97	67.35	643
HSA-MIR-3132	97.96	67.91	711
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-450B-3P	97.56	66.12	512
HSA-MIR-3909	97.55	66.78	887

Literature-anchored findings (GeneRIF, showing 2)

• Ahk1 is a scaffold protein in the HKR1 subbranch and prevents incorrect signal flow from Hkr1 to Kss1 (PMID:26787842)
• the methylation profile combination of HKR1, ROD1, and NLRC5 could be a promising biomarker for aging in Hainan centenarians (PMID:29394898)

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), ZNF596 (ENSG00000172748), ZNF80 (ENSG00000174255), ZNF266 (ENSG00000174652), ZNF25 (ENSG00000175395), ZNF77 (ENSG00000175691), ZNF169 (ENSG00000175787), ZNF404 (ENSG00000176222), ZNF491 (ENSG00000177599), ZNF620 (ENSG00000177842), ZNF619 (ENSG00000177873), ZNF329 (ENSG00000181894), ZFP90 (ENSG00000184939), ZNF566 (ENSG00000186017), ZNF529 (ENSG00000186020), ZNF749 (ENSG00000186230), ZNF555 (ENSG00000186300), ZNF70 (ENSG00000187792)

Protein

Protein identifiers

Zinc finger protein 875 — P10072 (reviewed: P10072)

Alternative names: Krueppel-related zinc finger protein 1, Protein HKR1

All UniProt accessions (18): A0A1B0GXI2, A0A494C010, P10072, F5H6A5, K7EJS1, K7EL05, K7EL22, K7EL36, K7EM51, K7EME6, K7EMG8, K7EMJ9, K7ENA5, K7EPW3, K7EQG8, K7ERA5, K7ES32, Q7Z6E1

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?
P10072-1	1	yes
P10072-2	2

RefSeq proteins (22): NP_001316690, NP_001316691, NP_001316692, NP_001316693, NP_001316694, NP_001316695, NP_001316696, NP_001316697, NP_001316698, NP_001316699, NP_001316700, NP_001316701, NP_001316702, NP_001316703, NP_001316704, NP_001316705, NP_001316706, NP_001316707, NP_001316708, NP_001340732, NP_001340733, NP_861451 (=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
IPR048414	PDRM9-like_Znf-C2H2	Domain

Pfam: PF00096, PF01352, PF21225

UniProt features (21 total): zinc finger region 13, sequence variant 3, chain 1, domain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10072-F1	66.73	0.25

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 53 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, OSMAN_BLADDER_CANCER_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, HATADA_METHYLATED_IN_LUNG_CANCER_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN, FIGUEROA_AML_METHYLATION_CLUSTER_1_UP, FIGUEROA_AML_METHYLATION_CLUSTER_3_UP, FIGUEROA_AML_METHYLATION_CLUSTER_4_UP, SNACANNNYSYAGA_UNKNOWN, ZWANG_DOWN_BY_2ND_EGF_PULSE, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, CBX5_TARGET_GENES, CEBPZ_TARGET_GENES, NPAT_TARGET_GENES, PRKDC_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 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), sequence-specific DNA binding (GO:0043565), 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
DNA binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

302 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF875	MYCL	P12524	498
ZNF875	OPN5	Q6U736	458
ZNF875	MYCN	P04198	431
ZNF875	RHO	P08100	399
ZNF875	NRAS	P01111	390
ZNF875	PLEKHH3	Q7Z736	353
ZNF875	OPN4	Q9UHM6	324
ZNF875	ERBB2	P04626	317
ZNF875	GTF2H2C	Q6P1K8	311
ZNF875	TCP10L	Q8TDR4	310
ZNF875	HEATR5B	Q9P2D3	305
ZNF875	APOE	P02649	305
ZNF875	EGFR	P00533	305
ZNF875	FAM110A	Q9BQ89	300
ZNF875	GPR135	Q8IZ08	289

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SLC9A8	AP1G1	psi-mi:“MI:0914”(association)	0.350
CDK11A	PRPF40A	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): HKR1 (Affinity Capture-RNA), HKR1 (Affinity Capture-MS), HKR1 (Affinity Capture-MS), HKR1 (Affinity Capture-MS), HKR1 (Affinity Capture-RNA), HKR1 (Affinity Capture-MS)

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: A0JPL0, A2A761, A3KN32, A3KN36, A6NFI3, A6NM28, A6QLU5, A6QPT6, A7MBI1, A8MTY0, B2RXC5, B4DU55, E9PYI1, O14978, O60765, O75467, O75820, O95780, P0C7X2, P0DKX0, P0DPD5, P10072, P15622, P16374, P17014, P17023, P17032, P17098, P51523, P51786, P52738, P52742, Q02975, Q06732, Q08DG8, Q08ER8, Q0VCB0, Q14590, Q14929, Q29RZ4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	10
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1265 predictions. Top by Δscore:

Variant	Effect	Δscore
19:37344788:TGTTA:T	donor_gain	1.0000
19:37344789:GTTAA:G	donor_gain	1.0000
19:37344790:TTA:T	donor_gain	1.0000
19:37347770:T:G	acceptor_gain	1.0000
19:37334778:GTTCC:G	donor_gain	0.9900
19:37334783:G:GG	donor_gain	0.9900
19:37335255:GAG:G	donor_gain	0.9900
19:37335255:GAGGT:G	donor_loss	0.9900
19:37335257:GGTG:G	donor_loss	0.9900
19:37335258:GTGAG:G	donor_loss	0.9900
19:37335259:T:G	donor_loss	0.9900
19:37344767:G:GT	donor_gain	0.9900
19:37344932:A:AG	acceptor_gain	0.9900
19:37344933:G:GG	acceptor_gain	0.9900
19:37347769:A:AG	acceptor_gain	0.9900
19:37347769:AT:A	acceptor_gain	0.9900
19:37347770:T:TA	acceptor_gain	0.9900
19:37347775:A:AG	acceptor_gain	0.9900
19:37347776:G:GG	acceptor_gain	0.9900
19:37347776:GAA:G	acceptor_gain	0.9900
19:37347869:CCAGG:C	donor_loss	0.9900
19:37347870:CAGG:C	donor_loss	0.9900
19:37347874:T:A	donor_loss	0.9900
19:37344745:A:AG	donor_gain	0.9800
19:37344745:A:G	donor_gain	0.9800
19:37344768:A:T	donor_gain	0.9800
19:37345022:G:GG	donor_gain	0.9800
19:37347774:CA:C	acceptor_loss	0.9800
19:37347775:AGAA:A	acceptor_loss	0.9800
19:37347776:G:GT	acceptor_loss	0.9800

AlphaMissense

4195 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:37362723:T:C	F310L	0.999
19:37362725:T:A	F310L	0.999
19:37362725:T:G	F310L	0.999
19:37362807:T:C	F338L	0.999
19:37362809:T:A	F338L	0.999
19:37362809:T:G	F338L	0.999
19:37362910:T:C	L372P	0.999
19:37362975:T:C	F394L	0.999
19:37362977:T:A	F394L	0.999
19:37362977:T:G	F394L	0.999
19:37363059:T:C	F422L	0.999
19:37363061:T:A	F422L	0.999
19:37363061:T:G	F422L	0.999
19:37363078:T:C	L428P	0.999
19:37363311:T:C	F506L	0.999
19:37363313:T:A	F506L	0.999
19:37363313:T:G	F506L	0.999
19:37362976:T:C	F394S	0.998
19:37363060:T:C	F422S	0.998
19:37363088:C:A	H431Q	0.998
19:37363088:C:G	H431Q	0.998
19:37363143:T:C	F450L	0.998
19:37363145:T:A	F450L	0.998
19:37363145:T:G	F450L	0.998
19:37363395:T:C	F534L	0.998
19:37363397:T:A	F534L	0.998
19:37363397:T:G	F534L	0.998
19:37362742:T:C	L316P	0.997
19:37362891:T:C	F366L	0.997
19:37362893:T:A	F366L	0.997

dbSNP variants (sampled 300 via entrez): RS1000052138 (19:37336560 A>G), RS1000110173 (19:37338279 C>G,T), RS1000212088 (19:37353030 C>T), RS1000225887 (19:37338045 T>A), RS1000249682 (19:37343586 T>C), RS1000287857 (19:37335126 G>A,C,T), RS1000304727 (19:37350468 C>T), RS1000368159 (19:37350236 C>G,T), RS1000544560 (19:37330387 C>G,T), RS1000604727 (19:37344910 C>A), RS1000795873 (19:37324988 C>T), RS1000825677 (19:37324794 A>G), RS1000942193 (19:37318788 A>G,T), RS1000954653 (19:37351349 T>C), RS1001000373 (19:37356705 C>A)

Disease associations

OMIM: gene MIM:165250 | disease phenotypes: MIM:617468, MIM:208150

GenCC curated gene-disease

Mondo (2): arthrogryposis multiplex congenita (MONDO:0015168), fetal akinesia deformation sequence 1 (MONDO:0100101)

Orphanet (2): Arthrogryposis multiplex congenita (Orphanet:1037), Fetal akinesia deformation sequence (Orphanet:994)

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
bisphenol A	affects cotreatment, decreases expression, increases methylation	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
Bortezomib	increases expression	1
Temozolomide	increases expression	1
Arsenic	increases methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Quercetin	increases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05393375	Not specified	COMPLETED	Arthrogryposis Multiplex Congenita in Pediatric Age: Correlation Between MUScular MRI and Functional Evaluation
NCT05673265	Not specified	UNKNOWN	Pediatric and Adult Registry for Patients With ARThrogryposis
NCT06130592	Not specified	UNKNOWN	Technical Feasibility Study of Ultrasound Muscle Imaging in Antenatal Ultrasound
NCT07360574	Not specified	NOT_YET_RECRUITING	Piezo2-related Arthrogryposis & physiopathOLOgy 3