ZNF704

Summary

ZNF704 (zinc finger protein 704, HGNC:32291) is a protein-coding gene on chromosome 8q21.13, encoding Zinc finger protein 704 (Q6ZNC4). Transcription factor which binds to RE2 sequence elements in the MYOD1 enhancer.

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 619279 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_001033723

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32291
Approved symbol	ZNF704
Name	zinc finger protein 704
Location	8q21.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16218, Gig1
Ensembl gene	ENSG00000164684
Ensembl biotype	protein_coding
Entrez	619279

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000327835, ENST00000517379, ENST00000517986, ENST00000519936, ENST00000520336, ENST00000522040

RefSeq mRNA: 2 — MANE Select: NM_001033723 NM_001033723, NM_001367783

CCDS: CCDS34913, CCDS94322

Canonical transcript exons

ENST00000327835 — 9 exons

Exon	Start	End
ENSE00001425307	80874571	80874781
ENSE00002111708	80670503	80670603
ENSE00003639390	80693004	80693107
ENSE00003657963	80687226	80687458
ENSE00003975906	80643035	80643129
ENSE00003975907	80659585	80659689
ENSE00003975908	80821374	80821615
ENSE00003975909	80664815	80665082
ENSE00003975910	80628451	80641477

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 96.44.

FANTOM5 (CAGE): breadth broad, TPM avg 4.0744 / max 187.9977, expressed in 805 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93724	3.7609	745
93725	0.2881	134
93726	0.0254	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	96.44	gold quality
kidney epithelium	UBERON:0004819	96.09	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.34	gold quality
oviduct epithelium	UBERON:0004804	94.75	gold quality
sural nerve	UBERON:0015488	94.36	gold quality
parotid gland	UBERON:0001831	93.96	gold quality
left ventricle myocardium	UBERON:0006566	93.96	silver quality
ganglionic eminence	UBERON:0004023	93.69	gold quality
calcaneal tendon	UBERON:0003701	93.57	gold quality
layer of synovial tissue	UBERON:0007616	93.17	gold quality
cerebellar vermis	UBERON:0004720	92.60	gold quality
endothelial cell	CL:0000115	92.35	gold quality
tibia	UBERON:0000979	92.26	gold quality
upper arm skin	UBERON:0004263	91.69	gold quality
myocardium	UBERON:0002349	91.60	gold quality
tendon of biceps brachii	UBERON:0008188	91.24	gold quality
tendon	UBERON:0000043	91.20	gold quality
visceral pleura	UBERON:0002401	90.97	gold quality
parietal pleura	UBERON:0002400	90.91	gold quality
corpus callosum	UBERON:0002336	90.84	gold quality
adrenal tissue	UBERON:0018303	90.49	gold quality
synovial joint	UBERON:0002217	90.41	gold quality
middle temporal gyrus	UBERON:0002771	90.20	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.12	gold quality
renal medulla	UBERON:0000362	89.99	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.73	gold quality
skin of hip	UBERON:0001554	89.68	gold quality
epithelium of mammary gland	UBERON:0003244	89.60	gold quality
mammary duct	UBERON:0001765	89.54	gold quality
seminal vesicle	UBERON:0000998	89.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	30.87
E-ANND-3	yes	12.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

791 targeting ZNF704, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692A	100.00	74.40	6850

Literature-anchored findings (GeneRIF, showing 3)

• tumor marker zinc finger protein 704 as part of a four gene transcript score has prognostic value for metastatic-lethal progression in men treated for localized prostate cancer (PMID:31376183)
• Circadian Rhythm Is Disrupted by ZNF704 in Breast Carcinogenesis. (PMID:32651256)
• Circular RNA HSDL2 promotes breast cancer progression via miR-7978 ZNF704 axis and regulating hippo signaling pathway. (PMID:38937788)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf704	ENSDARG00000061718
mus_musculus	Zfp704	ENSMUSG00000040209
rattus_norvegicus	Zfp704	ENSRNOG00000054426

Paralogs (2): SLC2A4RG (ENSG00000125520), ZNF395 (ENSG00000186918)

Protein

Protein identifiers

Zinc finger protein 704 — Q6ZNC4 (reviewed: Q6ZNC4)

All UniProt accessions (2): E5RGL7, Q6ZNC4

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor which binds to RE2 sequence elements in the MYOD1 enhancer.

Subcellular location. Nucleus.

Domain organisation. The CR1 and CR2 motifs mediate sequence-specific DNA binding, and are important for binding to the MYOD1 enhancer.

RefSeq proteins (2): NP_001028895, NP_001354712 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR052253	CR1/CR2-DNA-binding_regulator	Family

UniProt features (12 total): region of interest 4, modified residue 2, short sequence motif 2, chain 1, zinc finger region 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZNC4-F1	58.42	0.12

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): 228, 225

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 363 (showing top): GCACCTT_MIR18A_MIR18B, TGCACTT_MIR519C_MIR519B_MIR519A, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, PATIL_LIVER_CANCER, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, LIAO_METASTASIS, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, RICKMAN_HEAD_AND_NECK_CANCER_A, RIGGI_EWING_SARCOMA_PROGENITOR_UP, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GCACTTT_MIR175P_MIR20A_MIR106A_MIR106B_MIR20B_MIR519D, chr8q21

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

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA binding (GO:0003677), protein binding (GO:0005515), 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	2
transcription cis-regulatory region binding	2
transcription by RNA polymerase II	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription regulator activity	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF704	RFT1	Q96AA3	563
ZNF704	TMEM116	Q8NCL8	489
ZNF704	TBCB	Q99426	470
ZNF704	TBC1D31	Q96DN5	447
ZNF704	FHIP2A	Q5W0V3	445
ZNF704	MDN1	Q9NU22	445
ZNF704	DYNC1H1	Q14204	444
ZNF704	CWC27	Q6UX04	444
ZNF704	IMPA1	P29218	441
ZNF704	ELP2	Q6IA86	413
ZNF704	CCDC166	P0CW27	410
ZNF704	RABEP2	Q9H5N1	400
ZNF704	ZNF264	O43296	399
ZNF704	IPO11	Q9UI26	397
ZNF704	RALYL	Q86SE5	389

IntAct

10 interactions, top by confidence:

A	B	Type	Score
ZNF704	SAP30	psi-mi:“MI:0914”(association)	0.640
RECK	ZNF704	psi-mi:“MI:0915”(physical association)	0.560
ZNF704	KRT8	psi-mi:“MI:0915”(physical association)	0.400
ZNF704	HDAC3	psi-mi:“MI:0914”(association)	0.350
ZNF704	ADAM10	psi-mi:“MI:0914”(association)	0.350
	TTC8	psi-mi:“MI:0914”(association)	0.350

BioGRID (41): ZNF704 (Affinity Capture-MS), ZNF704 (Affinity Capture-MS), ZNF704 (Affinity Capture-Western), ZNF704 (Affinity Capture-Western), BTRC (Affinity Capture-MS), FBXW11 (Affinity Capture-MS), SAP30L (Affinity Capture-MS), SIN3A (Affinity Capture-MS), SUDS3 (Affinity Capture-MS), ING2 (Affinity Capture-MS), ARID4A (Affinity Capture-MS), SAP30 (Affinity Capture-MS), SAP130 (Affinity Capture-MS), ARID4B (Affinity Capture-MS), BRMS1L (Affinity Capture-MS)

ESM2 similar proteins: A0A088MLT8, A2AQ25, B3KU38, B5DF41, E9PSK7, O15079, O35274, P0DPB3, P0DPB4, P12755, P49140, P85299, Q0D2I5, Q14DQ1, Q1LY51, Q3B7M3, Q3SYW5, Q4KMA0, Q4R3X1, Q50H33, Q5F3L9, Q5FVG6, Q5RD40, Q5XKK7, Q60698, Q6ZNC4, Q6ZUS6, Q6ZWB6, Q80U23, Q80U62, Q80XA6, Q812A5, Q86YI8, Q8BXL9, Q8K2W6, Q8ND83, Q8NFH8, Q8QFX1, Q8TEK3, Q924W7

Diamond homologs: Q1LY51, Q6DFC8, Q6ZNC4, Q9ERQ3, Q9H8N7, Q9NR83

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2814 predictions. Top by Δscore:

Variant	Effect	Δscore
8:80659583:A:AC	donor_gain	1.0000
8:80659584:C:CA	donor_gain	1.0000
8:80659584:CT:C	donor_gain	1.0000
8:80659686:TGGC:T	acceptor_gain	1.0000
8:80664887:AGTCT:A	donor_gain	1.0000
8:80687221:CCAA:C	donor_loss	1.0000
8:80687223:AAC:A	donor_loss	1.0000
8:80687224:ACCT:A	donor_loss	1.0000
8:80687225:CCTTT:C	donor_gain	1.0000
8:80687234:T:A	donor_gain	1.0000
8:80687454:GCTCT:G	acceptor_gain	1.0000
8:80687455:CTCT:C	acceptor_gain	1.0000
8:80687455:CTCTC:C	acceptor_gain	1.0000
8:80687456:TCT:T	acceptor_gain	1.0000
8:80687456:TCTCT:T	acceptor_gain	1.0000
8:80687457:CT:C	acceptor_gain	1.0000
8:80687457:CTC:C	acceptor_gain	1.0000
8:80687458:TC:T	acceptor_loss	1.0000
8:80687458:TCT:T	acceptor_gain	1.0000
8:80687459:C:CC	acceptor_gain	1.0000
8:80687459:C:G	acceptor_gain	1.0000
8:80687463:A:C	acceptor_gain	1.0000
8:80821368:CCTTA:C	donor_loss	1.0000
8:80821369:CTTAC:C	donor_loss	1.0000
8:80821370:TTACC:T	donor_loss	1.0000
8:80821371:TACC:T	donor_loss	1.0000
8:80821372:A:AC	donor_gain	1.0000
8:80821372:A:T	donor_loss	1.0000
8:80821373:C:CA	donor_loss	1.0000
8:80821373:C:CC	donor_gain	1.0000

AlphaMissense

2711 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:80641375:G:C	F410L	1.000
8:80641375:G:T	F410L	1.000
8:80641376:A:G	F410S	1.000
8:80641377:A:G	F410L	1.000
8:80641378:C:A	R409S	1.000
8:80641378:C:G	R409S	1.000
8:80641379:C:A	R409M	1.000
8:80641384:G:C	C407W	1.000
8:80641385:C:A	C407F	1.000
8:80641385:C:G	C407S	1.000
8:80641385:C:T	C407Y	1.000
8:80641386:A:G	C407R	1.000
8:80641386:A:T	C407S	1.000
8:80641390:C:A	K405N	1.000
8:80641390:C:G	K405N	1.000
8:80641392:T:C	K405E	1.000
8:80641392:T:G	K405Q	1.000
8:80641393:C:A	K404N	1.000
8:80641393:C:G	K404N	1.000
8:80641394:T:A	K404M	1.000
8:80641394:T:G	K404T	1.000
8:80641395:T:C	K404E	1.000
8:80641396:C:A	W403C	1.000
8:80641396:C:G	W403C	1.000
8:80641397:C:G	W403S	1.000
8:80641398:A:G	W403R	1.000
8:80641398:A:T	W403R	1.000
8:80641401:G:T	R402S	1.000
8:80641402:G:C	C401W	1.000
8:80641403:C:A	C401F	1.000

dbSNP variants (sampled 300 via entrez): RS1000007419 (8:80870472 G>A,T), RS1000018860 (8:80817180 T>C), RS1000022630 (8:80856623 G>T), RS1000024029 (8:80741645 G>A), RS1000043167 (8:80785984 G>A,T), RS1000047244 (8:80704626 A>G), RS1000085542 (8:80700757 A>G), RS1000091609 (8:80835789 G>C), RS1000091967 (8:80690020 T>C,G), RS1000095818 (8:80743748 T>C), RS1000098898 (8:80865464 C>T), RS1000141489 (8:80644885 G>A,T), RS1000152182 (8:80853230 G>A,C), RS1000155038 (8:80702040 G>A), RS1000175027 (8:80713635 T>G)

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

8 associations (top):

Study	Trait	p-value
GCST002934_20	Zinc levels	8.000000e-06
GCST006421_4	Cannabis use	6.000000e-09
GCST006979_466	Heel bone mineral density	1.000000e-12
GCST008062_25	Blood urea nitrogen levels	4.000000e-10
GCST008758_3	Pre-treatment viral load in HIV-1 infection	4.000000e-17
GCST009391_1996	Metabolite levels	7.000000e-06
GCST009798_21	Asthma	6.000000e-22
GCST90011899_67	Aspartate aminotransferase levels	2.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007585	Cannabis use
EFO:0009270	heel bone mineral density
EFO:0010125	viral load
EFO:0010542	ureidopropionic acid measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
entinostat	decreases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Nickel	decreases expression	2
Cyclosporine	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
arsenite	decreases reaction, affects binding	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
afimoxifene	decreases expression, decreases reaction	1
sodium arsenite	decreases expression	1
cyanoginosin LR	decreases methylation, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
torcetrapib	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Doxorubicin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XW78	HEK293 eGFP-ZNF704	Transformed cell line	Female

Clinical trials (associated diseases)

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