ZNF251

Summary

ZNF251 (zinc finger protein 251, HGNC:13045) is a protein-coding gene on chromosome 8q24.3, encoding Zinc finger protein 251 (Q9BRH9). 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 act upstream of or within hematopoietic stem cell homeostasis. Predicted to be active in nucleus.

Source: NCBI Gene 90987 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 106 total
• MANE Select transcript: NM_138367

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13045
Approved symbol	ZNF251
Name	zinc finger protein 251
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198169
Ensembl biotype	protein_coding
Entrez	90987

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000292562, ENST00000524394, ENST00000525191, ENST00000530353, ENST00000861866, ENST00000861867, ENST00000861868, ENST00000861869, ENST00000861870, ENST00000861871, ENST00000861872, ENST00000917067, ENST00000965159, ENST00000965160

RefSeq mRNA: 1 — MANE Select: NM_138367 NM_138367

CCDS: CCDS47944

Canonical transcript exons

ENST00000292562 — 5 exons

Exon	Start	End
ENSE00001209809	144753683	144753796
ENSE00001209827	144755405	144755531
ENSE00001428382	144720909	144723382
ENSE00003367540	144754192	144754321
ENSE00003542789	144754696	144754803

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 92.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.0646 / max 46.0107, expressed in 1733 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95706	6.0494	1714
95707	0.7875	412
95705	0.2277	90

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	92.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.73	gold quality
cerebellar cortex	UBERON:0002129	92.70	gold quality
cerebellum	UBERON:0002037	92.54	gold quality
right lobe of thyroid gland	UBERON:0001119	91.38	gold quality
apex of heart	UBERON:0002098	90.91	gold quality
thyroid gland	UBERON:0002046	90.87	gold quality
left lobe of thyroid gland	UBERON:0001120	90.81	gold quality
pituitary gland	UBERON:0000007	89.71	gold quality
adenohypophysis	UBERON:0002196	89.34	gold quality
metanephros cortex	UBERON:0010533	89.23	gold quality
right uterine tube	UBERON:0001302	89.12	gold quality
body of uterus	UBERON:0009853	88.59	gold quality
endocervix	UBERON:0000458	88.44	gold quality
right ovary	UBERON:0002118	88.22	gold quality
right coronary artery	UBERON:0001625	87.83	gold quality
tibial nerve	UBERON:0001323	87.78	gold quality
left uterine tube	UBERON:0001303	87.41	gold quality
left ovary	UBERON:0002119	87.39	gold quality
ovary	UBERON:0000992	87.36	gold quality
lower esophagus mucosa	UBERON:0035834	87.24	gold quality
mucosa of stomach	UBERON:0001199	87.17	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.00	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.87	gold quality
myometrium	UBERON:0001296	86.84	gold quality
popliteal artery	UBERON:0002250	86.82	gold quality
tibial artery	UBERON:0007610	86.82	gold quality
fallopian tube	UBERON:0003889	86.73	gold quality
lower esophagus	UBERON:0013473	86.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.02

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2687.1	ZNF251	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605368

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

34 targeting ZNF251, 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-190A-3P	100.00	80.35	5520
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-1270	96.94	66.65	931

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp251	ENSMUSG00000022526
rattus_norvegicus	Zfp251	ENSRNOG00000030308

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 251 — Q9BRH9 (reviewed: Q9BRH9)

All UniProt accessions (2): Q9BRH9, H0YCK5

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.

RefSeq proteins (1): NP_612376* (*=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 (21 total): zinc finger region 14, cross-link 4, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRH9-F1	63.57	0.08

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 114, 157, 162, 403

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), hematopoietic stem cell homeostasis (GO:0061484), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): 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), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (1): nucleus (GO:0005634)

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
homeostasis of number of cells	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
double-stranded DNA binding	1
sequence-specific DNA binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

276 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF251	WFDC12	Q8WWY7	564
ZNF251	PNMA5	Q96PV4	559
ZNF251	CCDC57	Q2TAC2	499
ZNF251	MORN1	Q5T089	475
ZNF251	RNF113A	O15541	427
ZNF251	ZDBF2	Q9HCK1	411
ZNF251	MEGF6	O75095	404
ZNF251	PNMA3	Q9UL41	403
ZNF251	CCDC51	Q96ER9	395
ZNF251	ZDHHC9	Q9Y397	393
ZNF251	GPRIN2	O60269	380
ZNF251	FBXO40	Q9UH90	375
ZNF251	THAP3	Q8WTV1	373
ZNF251	EVA1B	Q9NVM1	371
ZNF251	PCDHGA4	Q9Y5G9	349

IntAct

27 interactions, top by confidence:

A	B	Type	Score
KRTAP10-9	ZNF251	psi-mi:“MI:0915”(physical association)	0.560
TRIM41	ZNF251	psi-mi:“MI:0915”(physical association)	0.560
FHL5	ZNF251	psi-mi:“MI:0915”(physical association)	0.560
ZNF251	E2	psi-mi:“MI:0915”(physical association)	0.490
PB2	ZNF251	psi-mi:“MI:0915”(physical association)	0.400
ZNF251	TRIM28	psi-mi:“MI:0915”(physical association)	0.400
ZNF251	PB2	psi-mi:“MI:0915”(physical association)	0.370
SMAD1	ZNF251	psi-mi:“MI:0915”(physical association)	0.370
ZNF460	ZNF320	psi-mi:“MI:0914”(association)	0.350
LTBP2	ZNF320	psi-mi:“MI:0914”(association)	0.350
ZNF251	E2	psi-mi:“MI:0915”(physical association)	0.000
BIN1	ZNF251	psi-mi:“MI:0915”(physical association)	0.000
ZNF251	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.000
ZNF251	TRIM41	psi-mi:“MI:0915”(physical association)	0.000
ZNF251	FHL5	psi-mi:“MI:0915”(physical association)	0.000
RBM11	ZNF251	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	ZNF251	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): ZNF251 (Two-hybrid), ZNF251 (Two-hybrid), ZNF251 (Two-hybrid), ZNF251 (Two-hybrid), ZNF251 (Two-hybrid), KRTAP10-9 (Two-hybrid), ZNF251 (Proximity Label-MS), ZNF251 (Affinity Capture-MS), ZNF251 (Affinity Capture-MS), ZNF251 (Affinity Capture-MS), ZNF251 (Two-hybrid), ZNF251 (Affinity Capture-MS), ZNF251 (Proximity Label-MS), ZNF251 (Two-hybrid), ZNF251 (Two-hybrid)

ESM2 similar proteins: A0JNB1, A1YF12, A1YG88, A2T759, B2RUI1, O43296, O75123, P10072, P17020, P17021, P17097, P51814, P52740, P52741, 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, Q8TAU3

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	95
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1207 predictions. Top by Δscore:

Variant	Effect	Δscore
8:144753677:TCTCA:T	donor_loss	1.0000
8:144753678:CTCA:C	donor_loss	1.0000
8:144753679:TCAC:T	donor_loss	1.0000
8:144753680:CA:C	donor_loss	1.0000
8:144753681:ACCTT:A	donor_loss	1.0000
8:144753682:C:G	donor_loss	1.0000
8:144753682:CCTTT:C	donor_gain	1.0000
8:144754207:T:A	donor_gain	1.0000
8:144753792:GAATC:G	acceptor_gain	0.9900
8:144753795:TC:T	acceptor_gain	0.9900
8:144753795:TCCTG:T	acceptor_loss	0.9900
8:144753796:CC:C	acceptor_gain	0.9900
8:144753797:C:CC	acceptor_gain	0.9900
8:144753798:T:G	acceptor_loss	0.9900
8:144754186:CCTCA:C	donor_loss	0.9900
8:144754187:CTCAC:C	donor_loss	0.9900
8:144754188:TCA:T	donor_loss	0.9900
8:144754190:A:AC	donor_gain	0.9900
8:144754190:AC:A	donor_gain	0.9900
8:144754190:ACCC:A	donor_loss	0.9900
8:144754191:C:CC	donor_gain	0.9900
8:144754191:C:CG	donor_loss	0.9900
8:144754191:CC:C	donor_gain	0.9900
8:144754208:C:A	donor_gain	0.9900
8:144754230:T:TA	donor_gain	0.9900
8:144754231:C:A	donor_gain	0.9900
8:144754320:TC:T	acceptor_gain	0.9900
8:144754320:TCC:T	acceptor_loss	0.9900
8:144754321:CC:C	acceptor_gain	0.9900
8:144754322:CTGCA:C	acceptor_loss	0.9900

AlphaMissense

4446 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:144722250:G:C	F470L	0.999
8:144722250:G:T	F470L	0.999
8:144722252:A:G	F470L	0.999
8:144722166:G:C	F498L	0.998
8:144722166:G:T	F498L	0.998
8:144722168:A:G	F498L	0.998
8:144722334:A:C	F442L	0.998
8:144722334:A:T	F442L	0.998
8:144722336:A:G	F442L	0.998
8:144722418:A:C	F414L	0.998
8:144722418:A:T	F414L	0.998
8:144722420:A:G	F414L	0.998
8:144722502:G:C	F386L	0.998
8:144722502:G:T	F386L	0.998
8:144722504:A:G	F386L	0.998
8:144722670:A:C	F330L	0.998
8:144722670:A:T	F330L	0.998
8:144722672:A:G	F330L	0.998
8:144722754:G:C	F302L	0.998
8:144722754:G:T	F302L	0.998
8:144722756:A:G	F302L	0.998
8:144722233:A:G	L476P	0.997
8:144722586:G:C	F358L	0.997
8:144722586:G:T	F358L	0.997
8:144722588:A:G	F358L	0.997
8:144722218:C:G	R481P	0.996
8:144722470:C:G	R397P	0.996
8:144722838:A:C	F274L	0.996
8:144722838:A:T	F274L	0.996
8:144722840:A:G	F274L	0.996

dbSNP variants (sampled 300 via entrez): RS1000093074 (8:144744017 T>A,G), RS1000254132 (8:144755702 A>C,G,T), RS1000431339 (8:144750185 C>T), RS1000488759 (8:144752428 T>C), RS1000520994 (8:144744513 G>C), RS1000612168 (8:144746782 C>G,T), RS1000624806 (8:144726911 G>A), RS1000658141 (8:144744742 G>A,C), RS1000798665 (8:144740730 T>TC), RS1000824292 (8:144739481 C>T), RS1000865575 (8:144749935 C>T), RS1000985602 (8:144731815 T>G), RS1001046253 (8:144746498 A>G), RS1001063168 (8:144731428 G>C), RS1001120272 (8:144726362 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

2 associations (top):

Study	Trait	p-value
GCST007005_4	Logical memory (immediate recall) in normal cognition	2.000000e-07
GCST90011898_110	Alanine aminotransferase levels	5.000000e-25

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Manganese	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Zinc	affects cotreatment, increases expression	1
Gold Compounds	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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