ZNF254

Summary

ZNF254 (zinc finger protein 254, HGNC:13047) is a protein-coding gene on chromosome 19p13, encoding Zinc finger protein 254 (O75437). May be involved in transcriptional regulation.

Zinc finger proteins have been shown to interact with nucleic acids and to have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See ZFP93 (MIM 604749) for additional information on zinc finger proteins.

Source: NCBI Gene 9534 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 154 total
• MANE Select transcript: NM_203282

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13047
Approved symbol	ZNF254
Name	zinc finger protein 254
Location	19p13
Locus type	gene with protein product
Status	Approved
Aliases	HD-ZNF1, BMZF-5
Ensembl gene	ENSG00000213096
Ensembl biotype	protein_coding
OMIM	604768
Entrez	9534

Gene structure

Transcript identifiers

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

ENST00000339642, ENST00000357002, ENST00000593783, ENST00000594886, ENST00000595187, ENST00000611359, ENST00000613065, ENST00000616028

RefSeq mRNA: 8 — MANE Select: NM_203282 NM_001278661, NM_001278662, NM_001278663, NM_001278664, NM_001278665, NM_001278677, NM_001278678, NM_203282

CCDS: CCDS32983, CCDS62622, CCDS62623, CCDS74323, CCDS74324

Canonical transcript exons

ENST00000357002 — 4 exons

Exon	Start	End
ENSE00003158150	24126254	24129968
ENSE00003174182	24087187	24087337
ENSE00003469299	24105940	24106066
ENSE00003521622	24106548	24106643

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 93.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.4915 / max 569.3175, expressed in 1800 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174932	23.5080	1786
174938	7.9046	1571
174936	1.6879	904
174931	0.5991	330
174937	0.3250	160
174939	0.2942	157
174940	0.1727	72

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	93.79	gold quality
ganglionic eminence	UBERON:0004023	90.38	gold quality
ventricular zone	UBERON:0003053	89.12	gold quality
calcaneal tendon	UBERON:0003701	88.75	gold quality
tendon	UBERON:0000043	88.34	gold quality
tendon of biceps brachii	UBERON:0008188	88.27	silver quality
cortical plate	UBERON:0005343	85.58	gold quality
adrenal tissue	UBERON:0018303	85.41	gold quality
medial globus pallidus	UBERON:0002477	84.94	gold quality
lower esophagus mucosa	UBERON:0035834	83.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.79	gold quality
globus pallidus	UBERON:0001875	82.52	gold quality
sperm	CL:0000019	82.50	silver quality
corpus callosum	UBERON:0002336	82.45	gold quality
amniotic fluid	UBERON:0000173	82.00	silver quality
oocyte	CL:0000023	81.87	silver quality
islet of Langerhans	UBERON:0000006	81.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.42	silver quality
colonic epithelium	UBERON:0000397	81.06	gold quality
left lobe of thyroid gland	UBERON:0001120	80.82	gold quality
thyroid gland	UBERON:0002046	80.81	gold quality
right lobe of thyroid gland	UBERON:0001119	80.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.13	gold quality
rectum	UBERON:0001052	80.05	gold quality
left ovary	UBERON:0002119	79.88	gold quality
male germ cell	CL:0000015	79.78	silver quality
tonsil	UBERON:0002372	79.55	gold quality
right ovary	UBERON:0002118	79.53	gold quality
endometrium	UBERON:0001295	79.39	gold quality
endocervix	UBERON:0000458	78.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

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 254 — O75437 (reviewed: O75437)

Alternative names: Bone marrow zinc finger 5, Hematopoietic cell-derived zinc finger protein 1, Zinc finger protein 539, Zinc finger protein 91-like

All UniProt accessions (7): A0A087WZJ7, A0A087X0A2, O75437, F5H2M4, M0QZY2, M0R2X5, Q7Z2R1

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?
O75437-1	1	yes
O75437-2	2

RefSeq proteins (8): NP_001265590, NP_001265591, NP_001265592, NP_001265593, NP_001265594, NP_001265606, NP_001265607, NP_975011* (*=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
IPR050589	Ikaros_C2H2-ZF	Family

Pfam: PF00096, PF01352, PF13465

UniProt features (25 total): zinc finger region 15, sequence variant 5, sequence conflict 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75437-F1	69.67	0.12

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 83 (showing top): MODULE_229, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, BLALOCK_ALZHEIMERS_DISEASE_UP, chr19p12, MODULE_123, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, MODULE_318, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, YAGI_AML_WITH_T_8_21_TRANSLOCATION, TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, PASINI_SUZ12_TARGETS_UP, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_UP, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

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-1 pathways:

Category	Pathways
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription	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
transition metal ion binding	1
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

492 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF254	ICA1	P78506	438
ZNF254	FAM124B	Q9H5Z6	418
ZNF254	RPP38	P78345	401
ZNF254	PKP2	Q99959	398
ZNF254	CD34	P28906	388
ZNF254	FAM219B	Q5XKK7	380
ZNF254	ASAP2	O43150	374
ZNF254	CCNI2	Q6ZMN8	374
ZNF254	MORN3	Q6PF18	362
ZNF254	CCDC148	Q8NFR7	348
ZNF254	LRP5L	A4QPB2	333
ZNF254	MZT2A	Q6P582	321
ZNF254	FBXO41	Q8TF61	308
ZNF254	SLC6A16	Q9GZN6	307
ZNF254	COMMD2	Q86X83	307

IntAct

9 interactions, top by confidence:

A	B	Type	Score
TRIM44	ODAD3	psi-mi:“MI:0914”(association)	0.530
ZNF254	ADRB2	psi-mi:“MI:0915”(physical association)	0.370
ECE1	ZNF254	psi-mi:“MI:0915”(physical association)	0.370
ZNF467	ZNF320	psi-mi:“MI:0914”(association)	0.350
LTBP2	ZNF320	psi-mi:“MI:0914”(association)	0.350
ZNF254	TRIM24	psi-mi:“MI:0914”(association)	0.350
TRIM44	ZNF254	psi-mi:“MI:0914”(association)	0.350
NDEL1	ZNF254	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): ZNF254 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), ZNF479 (Affinity Capture-MS), CYP24A1 (Affinity Capture-MS), TRIM24 (Affinity Capture-MS), ZNF254 (Affinity Capture-RNA), ZNF254 (Two-hybrid), TRIM28 (Affinity Capture-MS), ZNF254 (Affinity Capture-MS), CYP24A1 (Affinity Capture-MS), ZNF254 (Affinity Capture-MS), ZNF479 (Affinity Capture-MS), ZNF254 (Affinity Capture-MS), TRIM24 (Affinity Capture-MS), ZNF254 (Affinity Capture-RNA)

ESM2 similar proteins: A2VDQ7, A6NK75, A6NN14, A6NNF4, A8MQ14, A8MTY0, A8MXY4, B7Z6K7, E9QAG8, O43345, O75290, O75373, O75437, P0CJ79, P10751, P17017, P17019, P17035, P17038, P18749, P35789, P51522, Q03923, Q03938, Q05481, Q14585, Q3SYV7, Q4V348, Q5R5U3, Q5R8X1, Q5R9F0, Q5SXM1, Q6P5C7, Q6ZN08, Q6ZN57, Q6ZR52, Q86V71, Q86XN6, Q8IYB9, Q8N7Q3

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	138
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

706 predictions. Top by Δscore:

Variant	Effect	Δscore
19:24105936:CCAG:C	acceptor_loss	1.0000
19:24105937:CAG:C	acceptor_loss	1.0000
19:24105938:A:AG	acceptor_gain	1.0000
19:24105938:A:T	acceptor_loss	1.0000
19:24105938:AG:A	acceptor_gain	1.0000
19:24105938:AGG:A	acceptor_gain	1.0000
19:24105939:G:GG	acceptor_gain	1.0000
19:24105939:G:T	acceptor_loss	1.0000
19:24105939:GG:G	acceptor_gain	1.0000
19:24105939:GGG:G	acceptor_gain	1.0000
19:24105939:GGGA:G	acceptor_gain	1.0000
19:24105939:GGGAC:G	acceptor_gain	1.0000
19:24106063:CTGGG:C	donor_loss	1.0000
19:24106064:TGGGT:T	donor_loss	1.0000
19:24106066:GGT:G	donor_loss	1.0000
19:24106067:G:GG	donor_gain	1.0000
19:24106068:T:A	donor_loss	1.0000
19:24126252:AGGT:A	acceptor_loss	1.0000
19:24126253:GGTAT:G	acceptor_gain	1.0000
19:24087303:C:G	donor_gain	0.9900
19:24106065:GG:G	donor_gain	0.9900
19:24106066:GG:G	donor_gain	0.9900
19:24106069:G:GG	donor_loss	0.9900
19:24106072:GA:G	donor_gain	0.9900
19:24106545:CAGGT:C	acceptor_loss	0.9900
19:24106547:GGT:G	acceptor_gain	0.9900
19:24106640:CCAG:C	donor_loss	0.9900
19:24106643:GGTA:G	donor_loss	0.9900
19:24106645:T:A	donor_loss	0.9900
19:24126252:A:AG	acceptor_gain	0.9900

AlphaMissense

4368 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:24127495:T:C	F499L	0.985
19:24127497:T:A	F499L	0.985
19:24127497:T:G	F499L	0.985
19:24127411:T:C	F471L	0.982
19:24127413:T:A	F471L	0.982
19:24127413:T:G	F471L	0.982
19:24127579:T:C	F527L	0.974
19:24127581:T:A	F527L	0.974
19:24127581:T:G	F527L	0.974
19:24127075:T:C	F359L	0.973
19:24127077:T:A	F359L	0.973
19:24127077:T:G	F359L	0.973
19:24127327:T:C	F443L	0.972
19:24127329:T:A	F443L	0.972
19:24127329:T:G	F443L	0.972
19:24105973:T:C	F22L	0.968
19:24105975:C:A	F22L	0.968
19:24105975:C:G	F22L	0.968
19:24127747:T:C	F583L	0.966
19:24127749:T:A	F583L	0.966
19:24127749:T:G	F583L	0.966
19:24127663:T:C	F555L	0.964
19:24127665:T:A	F555L	0.964
19:24127665:T:G	F555L	0.964
19:24127243:T:C	F415L	0.961
19:24127245:T:A	F415L	0.961
19:24127245:T:G	F415L	0.961
19:24126907:T:C	F303L	0.959
19:24126909:T:A	F303L	0.959
19:24126909:T:G	F303L	0.959

dbSNP variants (sampled 300 via entrez): RS1000043260 (19:24032527 A>C), RS1000044442 (19:24129696 T>C), RS1000068731 (19:24117026 A>C), RS1000077972 (19:24053839 A>G), RS1000097765 (19:24129725 T>C), RS1000156144 (19:24104146 C>T), RS1000191725 (19:24053632 C>G,T), RS1000196943 (19:24094087 C>T), RS1000207484 (19:24062896 G>A), RS1000215722 (19:24049655 T>C), RS1000275259 (19:24053868 T>G), RS1000280808 (19:24059314 C>A), RS1000281781 (19:24065894 C>T), RS1000284233 (19:24083020 G>A), RS1000299216 (19:24071656 T>A,C)

Disease associations

OMIM: gene MIM:604768 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001692_12	Response to taxane treatment (docetaxel)	3.000000e-06
GCST001694_11	Response to taxane treatment (paclitaxel)	6.000000e-06
GCST003437_3	Discordance in emotional problems in monozygotic twins	6.000000e-06
GCST009863_26	Insulin-related traits (multivariate analysis)	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007803	emotional symptom measurement
EFO:0004467	insulin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	7
sodium arsenite	decreases expression, increases abundance, increases expression	3
trichostatin A	affects cotreatment, decreases expression	2
perfluorooctane sulfonic acid	decreases expression	2
Arsenic	increases expression, affects methylation, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Vehicle Emissions	decreases expression, decreases reaction	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Gallic Acid	decreases expression	1
Lead	affects expression	1
Mercury	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Nickel	decreases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Vanadates	decreases expression	1

Clinical trials (associated diseases)

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