ZNF654

Summary

ZNF654 (zinc finger protein 654, HGNC:25612) is a protein-coding gene on chromosome 3p11.1, encoding Zinc finger protein 654 (Q8IZM8). May be involved in transcriptional regulation.

Predicted to enable DNA binding activity and DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 55279 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_001350134

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25612
Approved symbol	ZNF654
Name	zinc finger protein 654
Location	3p11.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10997, FLJ21142
Ensembl gene	ENSG00000175105
Ensembl biotype	protein_coding
Entrez	55279

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 retained_intron

ENST00000473136, ENST00000623596, ENST00000636215, ENST00000894931, ENST00000894932, ENST00000894933, ENST00000963605, ENST00000963606

RefSeq mRNA: 8 — MANE Select: NM_001350134 NM_001350134, NM_001350135, NM_001350136, NM_001350137, NM_001366093, NM_001366095, NM_001366096, NM_001366097

CCDS: CCDS87110

Canonical transcript exons

ENST00000636215 — 9 exons

Exon	Start	End
ENSE00001220232	88141645	88144660
ENSE00001822403	88128809	88129011
ENSE00001841007	88135061	88135202
ENSE00001937859	88138705	88141048
ENSE00003791822	88126134	88126269
ENSE00003792777	88059255	88059505
ENSE00003794905	88086257	88086402
ENSE00003795095	88129687	88129826
ENSE00003796163	88113115	88113196

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.1822 / max 208.2473, expressed in 1778 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37456	11.1822	1778

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	98.84	gold quality
secondary oocyte	CL:0000655	95.41	gold quality
endothelial cell	CL:0000115	92.38	gold quality
oocyte	CL:0000023	92.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.36	gold quality
calcaneal tendon	UBERON:0003701	86.68	gold quality
germinal epithelium of ovary	UBERON:0001304	85.77	gold quality
visceral pleura	UBERON:0002401	83.97	gold quality
cartilage tissue	UBERON:0002418	83.71	gold quality
parietal pleura	UBERON:0002400	83.57	gold quality
gingival epithelium	UBERON:0001949	83.43	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.92	gold quality
pleura	UBERON:0000977	82.55	gold quality
sperm	CL:0000019	82.25	gold quality
amniotic fluid	UBERON:0000173	81.47	gold quality
tonsil	UBERON:0002372	81.22	gold quality
esophagus squamous epithelium	UBERON:0006920	81.14	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.86	gold quality
pigmented layer of retina	UBERON:0001782	80.75	gold quality
ventricular zone	UBERON:0003053	80.66	gold quality
upper leg skin	UBERON:0004262	80.54	gold quality
cortical plate	UBERON:0005343	80.37	gold quality
tibia	UBERON:0000979	80.17	gold quality
ganglionic eminence	UBERON:0004023	80.01	gold quality
gingiva	UBERON:0001828	79.73	gold quality
monocyte	CL:0000576	79.57	gold quality
male germ cell	CL:0000015	79.55	gold quality
postcentral gyrus	UBERON:0002581	79.43	gold quality
leukocyte	CL:0000738	79.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.55
E-GEOD-100618	no	249.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf654	ENSDARG00000079350
mus_musculus	Zfp654	ENSMUSG00000047141
rattus_norvegicus	Zfp654	ENSRNOG00000029956

Paralogs (2): RLF (ENSG00000117000), ZNF292 (ENSG00000188994)

Protein

Protein identifiers

Zinc finger protein 654 — Q8IZM8 (reviewed: Q8IZM8)

Alternative names: Melanoma-associated antigen

All UniProt accessions (1): Q8IZM8

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 (8): NP_001337063, NP_001337064, NP_001337065, NP_001337066, NP_001353022, NP_001353024, NP_001353025, NP_001353026 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR052251	GH-ZnFinger_Regulators	Family
IPR057986	TPR_Rlf/292/654	Domain

Pfam: PF00096, PF25420, PF25580

UniProt features (19 total): sequence conflict 7, zinc finger region 5, modified residue 2, region of interest 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZM8-F1	65.00	0.29

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 (2): 1123, 1127

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 141 (showing top): PAX4_01, FOXO4_01, FOXO1_01, AAAYRNCTG_UNKNOWN, CATRRAGC_UNKNOWN, AAACCAC_MIR140, TGCTGAY_UNKNOWN, OCT1_03, ZIC1_01, AAAGACA_MIR511, TGANTCA_AP1_C, TGACATY_UNKNOWN, NKX22_01, AFP1_Q6, NKX25_01

GO Biological Process (1): regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (5): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

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

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

897 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF654	C3orf38	Q5JPI3	666
ZNF654	CGGBP1	Q9UFW8	619
ZNF654	ZNF764	Q96H86	540
ZNF654	CCDC144A	A2RUR9	512
ZNF654	VSIG10	Q8N0Z9	507
ZNF654	DEFB104A	Q8WTQ1	497
ZNF654	ZNF770	Q6IQ21	490
ZNF654	ZNF366	Q8N895	456
ZNF654	ZBTB11	O95625	449
ZNF654	HLA-DRB5	Q30154	433
ZNF654	SHISA4	Q96DD7	432
ZNF654	TMEM120B	A0PK00	430
ZNF654	COL6A3	P12111	426
ZNF654	NRIP1	P48552	424
ZNF654	CCDC171	Q6TFL3	419

IntAct

0 interactions, top by confidence:

BioGRID (2): ZNF654 (Affinity Capture-MS), ZNF654 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0R4IXF6, A0JMR6, A5WW08, F4HRV8, O17482, O60934, O88974, O94988, P12757, P14629, P49021, P79457, Q08AW4, Q08D35, Q12789, Q28C33, Q2TB10, Q3B7T1, Q3UD82, Q3UWM4, Q498F0, Q5F363, Q5F3F2, Q5FWP4, Q5HYC2, Q5JSH3, Q5R431, Q5R7T9, Q5R9R1, Q5RGA4, Q5VVJ2, Q60665, Q63505, Q69Z66, Q6GQV7, Q6INA9, Q6NVE8, Q6P256, Q6ZMT4, Q8C5W4

Diamond homologs: O60281, O60315, Q13129, Q8IZM8, Q9DAU9, Q9R0G7, Q9Z2U2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

346 predictions. Top by Δscore:

Variant	Effect	Δscore
3:88058914:T:TA	donor_gain	0.9900
3:88141049:G:GG	donor_gain	0.9900
3:88058802:AGCT:A	donor_gain	0.9800
3:88058803:G:C	donor_gain	0.9800
3:88141045:GAAA:G	donor_gain	0.9800
3:88058798:C:A	donor_gain	0.9700
3:88058915:C:A	donor_gain	0.9700
3:88141046:A:T	donor_gain	0.9700
3:88058805:T:TA	donor_gain	0.9600
3:88058918:T:TA	donor_gain	0.9300
3:88141044:TGAAA:T	donor_gain	0.9300
3:88141045:GAAAG:G	donor_gain	0.9300
3:88141637:TTTTA:T	acceptor_loss	0.9300
3:88141638:TTTAC:T	acceptor_loss	0.9300
3:88141639:TTACA:T	acceptor_loss	0.9300
3:88141640:TACA:T	acceptor_loss	0.9300
3:88141641:ACAG:A	acceptor_loss	0.9300
3:88141642:CAGGT:C	acceptor_loss	0.9300
3:88141644:G:T	acceptor_loss	0.9300
3:88141047:AA:A	donor_gain	0.9200
3:88141050:T:TG	donor_loss	0.9200
3:88141051:AAGTC:A	donor_loss	0.9200
3:88141052:AGTCT:A	donor_loss	0.9100
3:88141053:G:C	donor_loss	0.9100
3:88141636:GTTTT:G	acceptor_loss	0.9100
3:88141643:A:AG	acceptor_gain	0.9100
3:88141644:G:GG	acceptor_gain	0.9100
3:88139237:A:AG	donor_gain	0.9000
3:88141631:GTTCT:G	acceptor_loss	0.8900
3:88058896:A:AT	donor_gain	0.8800

AlphaMissense

7563 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:88139389:T:C	C27R	1.000
3:88139317:T:C	C3R	0.999
3:88139353:C:A	H15N	0.999
3:88139353:C:G	H15D	0.999
3:88139355:T:A	H15Q	0.999
3:88139355:T:G	H15Q	0.999
3:88139357:C:A	A16D	0.999
3:88139365:C:G	H19D	0.999
3:88139390:G:A	C27Y	0.999
3:88139391:T:G	C27W	0.999
3:88139398:T:C	C30R	0.999
3:88139399:G:A	C30Y	0.999
3:88139410:T:C	F34L	0.999
3:88139411:T:C	F34S	0.999
3:88139412:T:A	F34L	0.999
3:88139412:T:G	F34L	0.999
3:88139437:C:G	H43D	0.999
3:88139439:T:A	H43Q	0.999
3:88139439:T:G	H43Q	0.999
3:88139911:T:C	C201R	0.999
3:88140034:T:A	C242S	0.999
3:88140034:T:C	C242R	0.999
3:88140035:G:C	C242S	0.999
3:88140043:T:C	C245R	0.999
3:88140051:G:C	R247S	0.999
3:88140051:G:T	R247S	0.999
3:88140082:C:G	H258D	0.999
3:88140084:C:A	H258Q	0.999
3:88140084:C:G	H258Q	0.999
3:88140118:T:C	C270R	0.999

dbSNP variants (sampled 300 via entrez): RS1000021226 (3:88072811 A>C,G), RS1000088188 (3:88071515 G>A), RS1000198310 (3:88143149 C>G,T), RS1000255636 (3:88143402 C>T), RS1000302459 (3:88110295 A>G), RS1000429451 (3:88060099 G>A,C), RS1000458099 (3:88073305 CAAAAA>C,CAAAA), RS1000460330 (3:88103599 A>T), RS1000569410 (3:88091998 AATCTT>A), RS1000621905 (3:88099189 T>C), RS1000690018 (3:88097703 G>A), RS1000756065 (3:88061643 A>G), RS1000767204 (3:88104805 C>T), RS1000862349 (3:88060363 T>C), RS1000870695 (3:88079589 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

1 associations (top):

Study	Trait	p-value
GCST002541_50	Menarche (age at onset)	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	3
sodium arsenite	increases abundance, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Formaldehyde	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
nickel chloride	increases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Copper	affects binding, increases expression	1
Coumestrol	decreases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Naphthoquinones	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_HD36	HEK293 eGFP-ZNF654	Transformed cell line	Female

Clinical trials (associated diseases)

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