ZNF768

Summary

ZNF768 (zinc finger protein 768, HGNC:26273) is a protein-coding gene on chromosome 16p11.2, encoding Zinc finger protein 768 (Q9H5H4). Binds to mammalian-wide interspersed repeat (MIRs) sequences in euchromatin and promoter regions of genes at the consensus sequence 5’-GCTGTGTG-[N20]-CCTCTCTG-3’, consisting of two anchor regions connected by a linker region; the linker region probably does not contribute to the….

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

Source: NCBI Gene 79724 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_024671

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26273
Approved symbol	ZNF768
Name	zinc finger protein 768
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23436
Ensembl gene	ENSG00000169957
Ensembl biotype	protein_coding
OMIM	618032
Entrez	79724

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000380412, ENST00000562803

RefSeq mRNA: 1 — MANE Select: NM_024671 NM_024671

CCDS: CCDS10681

Canonical transcript exons

ENST00000380412 — 2 exons

Exon	Start	End
ENSE00000871524	30524004	30526051
ENSE00001028718	30526326	30526566

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 96.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.0011 / max 110.0044, expressed in 1708 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157057	5.9767	1662
157058	2.0244	1166

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	96.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.55	gold quality
mucosa of transverse colon	UBERON:0004991	95.30	gold quality
tendon of biceps brachii	UBERON:0008188	94.46	gold quality
gastrocnemius	UBERON:0001388	94.16	gold quality
muscle of leg	UBERON:0001383	93.50	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.24	gold quality
body of tongue	UBERON:0011876	92.63	gold quality
ventricular zone	UBERON:0003053	92.39	gold quality
heart left ventricle	UBERON:0002084	92.17	gold quality
muscle organ	UBERON:0001630	92.04	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.98	gold quality
vena cava	UBERON:0004087	91.97	silver quality
transverse colon	UBERON:0001157	91.96	gold quality
lower esophagus	UBERON:0013473	91.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.95	gold quality
cardiac ventricle	UBERON:0002082	91.92	gold quality
nipple	UBERON:0002030	91.59	gold quality
right atrium auricular region	UBERON:0006631	91.08	gold quality
fundus of stomach	UBERON:0001160	91.04	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.94	gold quality
tongue	UBERON:0001723	90.87	gold quality
ganglionic eminence	UBERON:0004023	90.83	gold quality
pylorus	UBERON:0001166	90.75	gold quality
right testis	UBERON:0004534	90.70	gold quality
left testis	UBERON:0004533	90.60	gold quality
lower esophagus mucosa	UBERON:0035834	90.55	gold quality
cardiac atrium	UBERON:0002081	90.50	gold quality
heart	UBERON:0000948	90.44	gold quality
renal medulla	UBERON:0000362	90.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.36

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1731.1	ZNF768	More than 3 adjacent zinc fingers
MA1731.2	ZNF768	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:30476274

miRNA regulators (miRDB)

12 targeting ZNF768, 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-1976	99.74	65.48	1127
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-203B-3P	97.82	66.27	979
HSA-MIR-4680-5P	96.43	67.15	893

Literature-anchored findings (GeneRIF, showing 2)

• High ZNF768 expression is associated with colorectal cancer. (PMID:25875936)
• A report on the specific binding of zinc finger protein ZNF768 to the sequence motif GCTGTGTG (N20) CCTCTCTG in the core region of mammalian-wide interspersed repeats. (PMID:30476274)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp768	ENSMUSG00000047371
rattus_norvegicus	Zfp768	ENSRNOG00000029490

Paralogs (51): WIZ (ENSG00000011451), ZNF416 (ENSG00000083817), MYNN (ENSG00000085274), PRDM4 (ENSG00000110851), PRDM2 (ENSG00000116731), ZBTB17 (ENSG00000116809), ZNF644 (ENSG00000122482), GZF1 (ENSG00000125812), ZNF426 (ENSG00000130818), ZNF287 (ENSG00000141040), ZNF697 (ENSG00000143067), ZNF687 (ENSG00000143373), ZNF214 (ENSG00000149050), ZNF547 (ENSG00000152433), ZNF776 (ENSG00000152443), ZNF230 (ENSG00000159882), ZNF222 (ENSG00000159885), ZNF233 (ENSG00000159915), ZNF333 (ENSG00000160961), ZNF319 (ENSG00000166188), ZNF592 (ENSG00000166716), ZNF646 (ENSG00000167395), ZNF507 (ENSG00000168813), ZNF417 (ENSG00000173480), ZNF408 (ENSG00000175213), ZBTB41 (ENSG00000177888), ZNF223 (ENSG00000178386), ZNF852 (ENSG00000178917), ZNF784 (ENSG00000179922), ZNF572 (ENSG00000180938), ZNF707 (ENSG00000181135), ZNF746 (ENSG00000181220), ZNF467 (ENSG00000181444), ZNF530 (ENSG00000183647), ZNF17 (ENSG00000186272), ZNF527 (ENSG00000189164), ZKSCAN7 (ENSG00000196345), ZNF34 (ENSG00000196378), ZNF774 (ENSG00000196391), ZNF777 (ENSG00000196453)

Protein

Protein identifiers

Zinc finger protein 768 — Q9H5H4 (reviewed: Q9H5H4)

All UniProt accessions (2): Q9H5H4, H3BS42

UniProt curated annotations — full annotation on UniProt →

Function. Binds to mammalian-wide interspersed repeat (MIRs) sequences in euchromatin and promoter regions of genes at the consensus sequence 5’-GCTGTGTG-[N20]-CCTCTCTG-3’, consisting of two anchor regions connected by a linker region; the linker region probably does not contribute to the binding specificity. Required for cell homeostasis. May be involved in transcriptional regulation.

Subunit / interactions. Interacts (via zinc-finger domains) with TP53 (via N-terminus); interaction might be facilitated by TP53 oligomerization state. Interacts with ELP3.

Subcellular location. Nucleus. Chromosome.

Post-translational modifications. May be phosphorylated at residue ‘Ser-5’ of the tandem heptapeptide repeats in the N-terminus. Phosphorylation might be increased upon RAS pathway activation and negatively regulate protein stability.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_078947* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000684	RNA_pol_II_repeat_euk	Repeat
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF05001

UniProt features (60 total): modified residue 31, zinc finger region 10, mutagenesis site 10, compositionally biased region 4, region of interest 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H5H4-F1	64.46	0.17

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 (31): 17, 18, 23, 27, 33, 62, 69, 76, 83, 90, 97, 104, 107, 111, 118, 125, 128, 132, 135, 139 …

Mutagenesis-validated functional residues (10):

Position	Phenotype
62	increases protein stability.
69	increases protein stability.
76	increases protein stability.
83	increases protein stability.
90	no effect on protein stability.
97	no effect on protein stability.
125	no effect on protein stability.
132	no effect on protein stability.
139	increases protein stability.
160	no effect on protein stability.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 97 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, TGACCTY_ERR1_Q2, SP1_Q2_01, NF1_Q6_01, chr16p11, AACTTT_UNKNOWN, RYTTCCTG_ETS2_B, P300_01, WHN_B, RFX1_02, TGTYNNNNNRGCARM_UNKNOWN, NERF_Q2, CETS1P54_01

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366)

GO Molecular Function (8): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), RNA binding (GO:0003723), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

898 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF768	ZNF511	Q8NB15	485
ZNF768	DNMBP	Q6XZF7	473
ZNF768	ZNF638	Q14966	447
ZNF768	C6orf163	Q5TEZ5	434
ZNF768	USP36	Q9P275	429
ZNF768	CFAP107	Q8N1D5	418
ZNF768	KAT8	Q9H7Z6	418
ZNF768	ZNF853	P0CG23	405
ZNF768	ITGAL	P20701	404
ZNF768	RAPGEF1	Q13905	400
ZNF768	ZNF346	Q9UL40	393
ZNF768	ZNF521	Q96K83	389
ZNF768	ZNF148	Q9UQR1	384
ZNF768	ZNF232	Q9UNY5	378
ZNF768	WHAMM	Q8TF30	377

IntAct

158 interactions, top by confidence:

A	B	Type	Score
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
GABARAP	IPO5	psi-mi:“MI:0914”(association)	0.590
PIN1	ZNF768	psi-mi:“MI:0915”(physical association)	0.560
EFEMP2	ZNF768	psi-mi:“MI:0915”(physical association)	0.560
ZNF768	ZNF330	psi-mi:“MI:0915”(physical association)	0.560
	ZNF768	psi-mi:“MI:0915”(physical association)	0.560
ZNF250	ZNF768	psi-mi:“MI:0915”(physical association)	0.560
CLK2	ZNF768	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	ZNF768	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	ZNF768	psi-mi:“MI:0915”(physical association)	0.560
ZNF417	ZNF768	psi-mi:“MI:0915”(physical association)	0.560
ZNF768	ZNF835	psi-mi:“MI:0915”(physical association)	0.560
EMG1	ZNF768	psi-mi:“MI:0915”(physical association)	0.560
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
NIFK	RSL1D1	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
SULF2	UBTF	psi-mi:“MI:0914”(association)	0.530
ZNF768	RPS10	psi-mi:“MI:0915”(physical association)	0.500
ZNF277	ZNF768	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (141): ZNF768 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS), ZNF768 (Proximity Label-MS), ZNF768 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YY54, A4FU49, A5D7L8, E9Q6E9, F1LWT0, O14686, O15069, P21263, P79386, Q149B8, Q28256, Q2EG98, Q4JF29, Q4R729, Q5HY64, Q5JRC9, Q6P5H2, Q6PDK2, Q70KF4, Q80UE6, Q8CHD8, Q8K327, Q8N1P7, Q8N5Q1, Q8N693, Q8N7U7, Q8NA70, Q8R0T2, Q96DU7, Q96J92, Q96JM3, Q96QH2, Q99KW3, Q99PG2, Q9BE18, Q9BG94, Q9CWU5, Q9DGW5, Q9H5H4, Q9H7P9

Diamond homologs: A1YEV9, A1YG26, A1YG60, A2ANX9, A2T712, A2T736, A2T7L7, A3KN32, A7Y7X5, B0K011, E9Q6W4, O14771, O15391, O35738, O43474, O62836, O95125, P08048, P0CG23, P10925, P17010, P17012, P17022, P17041, P20662, P24399, P25490, P28698, P51815, P52736, P57682, P80944, P86413, P98182, Q00899, Q01611, Q07231, Q08DS3, Q14929, Q15776

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peptide chain elongation	18	25.9×	7e-19
Viral mRNA Translation	18	25.9×	7e-19
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	18	25.7×	7e-19
Selenocysteine synthesis	18	24.6×	1e-18
Eukaryotic Translation Termination	18	24.6×	1e-18
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	18	24.1×	1e-18
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	18	24.1×	1e-18
Formation of a pool of free 40S subunits	18	22.9×	2e-18

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	19	27.9×	8e-20
translation	19	15.5×	5e-15
RNA processing	7	12.2×	3e-04
rRNA processing	10	11.2×	5e-06
ribosomal small subunit biogenesis	6	10.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

262 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30526325:CCT:C	donor_gain	1.0000
16:30526052:C:CC	acceptor_gain	0.9900
16:30526052:CTGCA:C	acceptor_loss	0.9900
16:30526261:C:A	donor_gain	0.9900
16:30526316:C:CA	donor_gain	0.9900
16:30526322:TCACC:T	donor_loss	0.9900
16:30526325:C:CT	donor_loss	0.9900
16:30526373:T:TA	donor_gain	0.9900
16:30526053:T:C	acceptor_loss	0.9800
16:30526048:TTGC:T	acceptor_gain	0.9700
16:30526056:A:T	acceptor_gain	0.9700
16:30526319:T:TA	donor_gain	0.9700
16:30526329:TGAGG:T	donor_gain	0.9700
16:30526049:TGC:T	acceptor_gain	0.9600
16:30526055:C:CT	acceptor_gain	0.9600
16:30526059:A:AC	acceptor_gain	0.9600
16:30526257:C:CA	donor_gain	0.9600
16:30526324:A:AC	donor_gain	0.9600
16:30526325:C:CC	donor_gain	0.9600
16:30526050:GC:G	acceptor_gain	0.9500
16:30526051:CC:C	acceptor_gain	0.9500
16:30526273:AGCC:A	donor_gain	0.9500
16:30526047:GTTGC:G	acceptor_gain	0.9400
16:30526332:G:C	donor_gain	0.9300
16:30526282:T:TA	donor_gain	0.9200
16:30526059:A:C	acceptor_gain	0.9100
16:30526323:CACC:C	donor_loss	0.8900
16:30526276:C:A	donor_gain	0.8700
16:30526653:A:AC	donor_gain	0.8600
16:30526654:C:CC	donor_gain	0.8600

AlphaMissense

3568 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30524557:A:G	L528P	1.000
16:30524574:G:C	F522L	1.000
16:30524574:G:T	F522L	1.000
16:30524576:A:G	F522L	1.000
16:30524658:G:C	F494L	1.000
16:30524658:G:T	F494L	1.000
16:30524660:A:G	F494L	1.000
16:30524742:G:C	F466L	1.000
16:30524742:G:T	F466L	1.000
16:30524744:A:G	F466L	1.000
16:30525078:G:C	F354L	1.000
16:30525078:G:T	F354L	1.000
16:30525080:A:G	F354L	1.000
16:30525145:A:G	L332P	1.000
16:30525162:G:C	F326L	1.000
16:30525162:G:T	F326L	1.000
16:30525164:A:G	F326L	1.000
16:30525207:G:C	H311Q	1.000
16:30525207:G:T	H311Q	1.000
16:30525214:C:G	R309P	1.000
16:30525219:G:C	H307Q	1.000
16:30525219:G:T	H307Q	1.000
16:30525221:G:C	H307D	1.000
16:30525229:A:G	L304P	1.000
16:30525246:G:C	F298L	1.000
16:30525246:G:T	F298L	1.000
16:30525247:A:G	F298S	1.000
16:30525248:A:G	F298L	1.000
16:30525248:A:T	F298I	1.000
16:30525291:G:C	H283Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000200368 (16:30525419 C>A,T), RS1000220204 (16:30527561 C>A,G), RS1000720862 (16:30527392 G>C), RS1000868120 (16:30530020 G>A,T), RS1000978717 (16:30530482 G>A), RS1001435015 (16:30526140 T>C), RS1002057521 (16:30527931 T>G), RS1002197056 (16:30530932 C>T), RS1002284318 (16:30533754 A>G), RS1002328110 (16:30524123 C>T), RS1002439579 (16:30524381 A>C), RS1002663155 (16:30523514 A>G), RS1002718125 (16:30531243 C>T), RS1002879706 (16:30527321 C>G,T), RS1002994276 (16:30527491 T>C)

Disease associations

OMIM: gene MIM:618032 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, decreases expression	3
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
geraniol	increases expression	1
lead acetate	increases expression	1
sodium arsenite	increases expression	1
coumarin	increases phosphorylation	1
perfluorooctane sulfonic acid	increases expression	1
Bortezomib	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydralazine	increases expression, affects cotreatment	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Selenium	increases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Vitamin E	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, increases 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_XW81	HEK293 eGFP-ZNF768	Transformed cell line	Female

Clinical trials (associated diseases)

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