ZNF257

Summary

ZNF257 (zinc finger protein 257, HGNC:13498) is a protein-coding gene on chromosome 19p12, encoding Zinc finger protein 257 (Q9Y2Q1). 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 DNA-templated transcription. Predicted to be located in nucleus.

Source: NCBI Gene 113835 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_033468

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13498
Approved symbol	ZNF257
Name	zinc finger protein 257
Location	19p12
Locus type	gene with protein product
Status	Approved
Aliases	BMZF-4
Ensembl gene	ENSG00000197134
Ensembl biotype	protein_coding
OMIM	606957
Entrez	113835

Gene structure

Transcript identifiers

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

ENST00000435820, ENST00000594363, ENST00000594947, ENST00000596471, ENST00000597796, ENST00000597927, ENST00000600162, ENST00000651332

RefSeq mRNA: 4 — MANE Select: NM_033468 NM_001316996, NM_001316997, NM_001316998, NM_033468

CCDS: CCDS46030

Canonical transcript exons

ENST00000594947 — 4 exons

Exon	Start	End
ENSE00003023642	22087977	22091480
ENSE00003485488	22072809	22072935
ENSE00003530360	22052484	22052635
ENSE00003608121	22073469	22073564

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 83.42.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2709 / max 96.0484, expressed in 708 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174899	2.1613	698
174900	0.1096	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.42	gold quality
oocyte	CL:0000023	76.01	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.23	gold quality
ventricular zone	UBERON:0003053	73.45	gold quality
buccal mucosa cell	CL:0002336	72.96	silver quality
secondary oocyte	CL:0000655	72.80	silver quality
islet of Langerhans	UBERON:0000006	71.17	gold quality
calcaneal tendon	UBERON:0003701	68.96	gold quality
lymph node	UBERON:0000029	68.65	gold quality
ganglionic eminence	UBERON:0004023	68.54	gold quality
pancreas	UBERON:0001264	67.82	gold quality
body of pancreas	UBERON:0001150	67.62	gold quality
left ovary	UBERON:0002119	67.54	gold quality
right ovary	UBERON:0002118	67.15	gold quality
granulocyte	CL:0000094	66.97	gold quality
right lobe of thyroid gland	UBERON:0001119	65.68	gold quality
lower esophagus mucosa	UBERON:0035834	65.62	gold quality
left lobe of thyroid gland	UBERON:0001120	65.43	gold quality
adrenal tissue	UBERON:0018303	65.39	gold quality
smooth muscle tissue	UBERON:0001135	65.04	gold quality
ovary	UBERON:0000992	64.87	gold quality
cortical plate	UBERON:0005343	64.70	gold quality
leukocyte	CL:0000738	64.60	gold quality
thyroid gland	UBERON:0002046	64.58	gold quality
monocyte	CL:0000576	64.13	gold quality
mononuclear cell	CL:0000842	63.99	gold quality
right atrium auricular region	UBERON:0006631	63.98	gold quality
spleen	UBERON:0002106	63.79	gold quality
gall bladder	UBERON:0002110	63.73	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	63.73	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	166.83
E-ANND-3	no	5.63

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1710.1	ZNF257	More than 3 adjacent zinc fingers
MA1710.2	ZNF257	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:27852650

miRNA regulators (miRDB)

145 targeting ZNF257, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AT-5P	99.96	70.83	2666
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-LET-7C-3P	99.95	73.42	2862

Literature-anchored findings (GeneRIF, showing 1)

• one of the breakpoints disrupts the transcription factor gene ZNF257, causing a significant reduction in the total expression level of this gene in lymphoblastoid cell lines (PMID:26427027)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000099025

Paralogs (18): ZNF430 (ENSG00000118620), ZNF92 (ENSG00000146757), ZNF66 (ENSG00000160229), ZNF22 (ENSG00000165512), ZNF680 (ENSG00000173041), ZNF114 (ENSG00000178150), ZFP41 (ENSG00000181638), ZNF730 (ENSG00000183850), ZNF479 (ENSG00000185177), ZNF626 (ENSG00000188171), ZNF431 (ENSG00000196705), ZNF100 (ENSG00000197020), ZNF98 (ENSG00000197360), ZNF675 (ENSG00000197372), ZNF273 (ENSG00000198039), ZNF737 (ENSG00000237440), ZNF253 (ENSG00000256771), ZNF723 (ENSG00000268696)

Protein

Protein identifiers

Zinc finger protein 257 — Q9Y2Q1 (reviewed: Q9Y2Q1)

Alternative names: Bone marrow zinc finger 4

All UniProt accessions (6): A0A494C0E0, Q9Y2Q1, M0QXX9, M0QYA6, M0R0N1, M0R321

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 (4)

UniProt ID	Names	Canonical?
Q9Y2Q1-1	1	yes
Q9Y2Q1-2	2
Q9Y2Q1-3	3
Q9Y2Q1-4	4

RefSeq proteins (4): NP_001303925, NP_001303926, NP_001303927, NP_258429* (*=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
IPR050636	C2H2-ZF_domain-containing	Family

Pfam: PF00096, PF01352

UniProt features (24 total): zinc finger region 13, sequence conflict 6, splice variant 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2Q1-F1	67.58	0.04

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins

MSigDB gene sets: 68 (showing top): chr19p12, HAMAI_APOPTOSIS_VIA_TRAIL_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, REACTOME_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, TAVAZOIE_METASTASIS, KRAS.AMP.LUNG_UP.V1_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ASH1L_TARGET_GENES, TAF9B_TARGET_GENES, MIR23A_3P_MIR23B_3P, MIR23C, MIR6809_3P, MIR3688_3P, MIR6833_3P, MIR4699_3P

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (5): 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), metal ion binding (GO:0046872)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	1
Regulation of endogenous retroelements	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
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	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
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF257	OR13C3	Q8NGS6	431
ZNF257	LRRC34	Q8IZ02	373
ZNF257	Q6GMV1	Q6GMV1	370
ZNF257	TTC16	Q8NEE8	368
ZNF257	C12orf42	Q96LP6	349
ZNF257	K7N7A8	K7N7A8	332
ZNF257	TSPYL6	Q8N831	327
ZNF257	H2BC3	P33778	312
ZNF257	C5orf63	A6NC05	310
ZNF257	LRRC46	Q96FV0	300
ZNF257	H1-1	Q02539	299
ZNF257	FAM53A	Q6NSI3	290
ZNF257	PTRH1	Q86Y79	287
ZNF257	DCAF4	Q8WV16	277
ZNF257	ZNF92	Q03936	272
ZNF257	TOR2A	Q5JU69	272

IntAct

2 interactions, top by confidence:

A	B	Type	Score
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
ZNF257	SSRP1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (6): ZNF257 (Proximity Label-MS), ZNF257 (Proximity Label-MS), ZNF257 (Affinity Capture-MS), ZNF257 (Affinity Capture-MS), ZNF257 (Cross-Linking-MS (XL-MS)), ZNF257 (Affinity Capture-RNA)

ESM2 similar proteins: A6NDX5, A6NK75, A6NNF4, A6NP11, B4DXR9, B7Z6K7, C9JN71, O43361, O75290, O75373, P0CJ79, P0DKX0, P17019, P17021, P17035, P17039, P35789, Q02386, Q03938, Q08AN1, Q13106, Q15928, Q3ZCX4, Q5R9F0, Q5SXM1, Q68EA5, Q6P9A1, Q6PDB4, Q6ZN06, Q6ZN08, Q6ZNG1, Q76KX8, Q86V71, Q86XN6, Q8IYB9, Q8N4W9, Q8NEP9, Q8TBZ8, Q8TC21, Q8TF32

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

611 predictions. Top by Δscore:

Variant	Effect	Δscore
19:22072803:TTTCA:T	acceptor_loss	1.0000
19:22072804:TTCA:T	acceptor_loss	1.0000
19:22072805:TCA:T	acceptor_loss	1.0000
19:22072806:CAGG:C	acceptor_loss	1.0000
19:22082734:A:AG	donor_gain	1.0000
19:22052633:ATGG:A	donor_loss	0.9900
19:22052636:GTGAG:G	donor_loss	0.9900
19:22052637:T:G	donor_loss	0.9900
19:22072807:A:AG	acceptor_gain	0.9900
19:22072807:AG:A	acceptor_gain	0.9900
19:22072808:G:GG	acceptor_gain	0.9900
19:22072808:GG:G	acceptor_gain	0.9900
19:22072808:GGGAC:G	acceptor_gain	0.9900
19:22072896:G:T	donor_gain	0.9900
19:22072934:GG:G	donor_gain	0.9900
19:22072935:GG:G	donor_gain	0.9900
19:22072950:A:AG	donor_gain	0.9900
19:22072951:G:GG	donor_gain	0.9900
19:22082734:A:G	donor_gain	0.9900
19:22087975:A:AG	acceptor_gain	0.9900
19:22087976:G:GG	acceptor_gain	0.9900
19:22087976:GTT:G	acceptor_gain	0.9900
19:22087976:GTTAT:G	acceptor_gain	0.9900
19:22052622:G:GT	donor_gain	0.9800
19:22052636:G:GG	donor_gain	0.9800
19:22052946:G:T	donor_gain	0.9800
19:22072807:AGG:A	acceptor_gain	0.9800
19:22072808:GGG:G	acceptor_gain	0.9800
19:22072931:CCTGG:C	donor_loss	0.9800
19:22072936:G:GT	donor_loss	0.9800

AlphaMissense

3743 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:22089152:T:C	F468L	0.987
19:22089154:T:A	F468L	0.987
19:22089154:T:G	F468L	0.987
19:22089236:T:C	F496L	0.986
19:22089238:T:A	F496L	0.986
19:22089238:T:G	F496L	0.986
19:22089068:T:C	F440L	0.984
19:22089070:T:A	F440L	0.984
19:22089070:T:G	F440L	0.984
19:22088807:T:C	F353L	0.981
19:22088809:T:A	F353L	0.981
19:22088809:T:G	F353L	0.981
19:22088462:T:C	F238L	0.978
19:22088464:T:A	F238L	0.978
19:22088464:T:G	F238L	0.978
19:22089243:G:C	R498P	0.978
19:22088723:T:C	F325L	0.976
19:22088725:T:A	F325L	0.976
19:22088725:T:G	F325L	0.976
19:22088891:T:C	F381L	0.976
19:22088893:T:A	F381L	0.976
19:22088893:T:G	F381L	0.976
19:22089171:T:C	L474P	0.969
19:22088814:G:C	R355P	0.959
19:22089320:T:C	F524L	0.952
19:22089322:T:A	F524L	0.952
19:22089322:T:G	F524L	0.952
19:22088546:T:C	F266L	0.950
19:22088548:T:A	F266L	0.950
19:22088548:T:G	F266L	0.950

dbSNP variants (sampled 300 via entrez): RS1000035476 (19:22057081 C>T), RS1000192239 (19:22072207 AT>A,ATT), RS1000214219 (19:22062103 C>T), RS1000214389 (19:22081648 C>T), RS1000401714 (19:22066230 A>G), RS1000436589 (19:22064071 C>T), RS1000468081 (19:22078233 A>G), RS1000548699 (19:22083416 A>G), RS1000610545 (19:22090016 A>G,T), RS1000682873 (19:22067416 C>A,T), RS1000736532 (19:22067773 G>A,C), RS1000763668 (19:22052746 G>A,T), RS1000819681 (19:22051291 A>G), RS1000904865 (19:22073820 T>C), RS1000942931 (19:22070171 T>C)

Disease associations

OMIM: gene MIM:606957 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002692_4	Body mass index (change over time)	3.000000e-06
GCST004713_11	Testicular germ cell tumor	2.000000e-08
GCST007847_81	Type 2 diabetes	5.000000e-11
GCST008366_20	Leukocyte telomere length	1.000000e-12
GCST008554_6	Atorvastatin-induced myopathy	4.000000e-06
GCST010118_73	Type 2 diabetes	7.000000e-23

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005937	longitudinal BMI measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
nickel sulfate	increases expression	1
cupric oxide	increases expression	1
CGP 52608	affects binding, increases reaction	1
Leflunomide	decreases expression	1
Ethanol	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	increases expression	1
Tetradecanoylphorbol Acetate	affects cotreatment, affects expression	1
Zinc	affects cotreatment, affects expression	1
Cadmium Chloride	increases abundance, increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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