ZNF689

Summary

ZNF689 (zinc finger protein 689, HGNC:25173) is a protein-coding gene on chromosome 16p11.2, encoding Transcriptional regulator SEHBP (C0HLU2). Plays a role in transcription regulation.

Enables histone binding activity. Involved in regulation of transcription by RNA polymerase II. Located in cytoplasm and nucleus.

Source: NCBI Gene 115509 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_138447

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25173
Approved symbol	ZNF689
Name	zinc finger protein 689
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90415, TIPUH1
Ensembl gene	ENSG00000156853
Ensembl biotype	protein_coding
OMIM	618033
Entrez	115509

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000287461, ENST00000563304, ENST00000564262, ENST00000565440, ENST00000565710, ENST00000566673, ENST00000924641

RefSeq mRNA: 1 — MANE Select: NM_138447 NM_138447

CCDS: CCDS10686

Canonical transcript exons

ENST00000287461 — 3 exons

Exon	Start	End
ENSE00001111831	30609837	30610389
ENSE00001305242	30602558	30605447
ENSE00003544717	30609525	30609638

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 97.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.3372 / max 82.8332, expressed in 1695 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157078	4.6093	1623
157077	1.4787	742
157073	0.0914	29
157076	0.0754	17
157075	0.0625	19
207839	0.0198	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.05	gold quality
secondary oocyte	CL:0000655	96.22	gold quality
pancreatic ductal cell	CL:0002079	92.42	gold quality
sperm	CL:0000019	91.85	gold quality
adult organism	UBERON:0007023	88.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.50	gold quality
tibialis anterior	UBERON:0001385	83.45	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.14	gold quality
testis	UBERON:0000473	82.96	gold quality
left testis	UBERON:0004533	82.71	gold quality
right testis	UBERON:0004534	81.72	gold quality
ileal mucosa	UBERON:0000331	81.16	gold quality
buccal mucosa cell	CL:0002336	80.05	silver quality
cortical plate	UBERON:0005343	79.48	gold quality
granulocyte	CL:0000094	79.37	gold quality
deltoid	UBERON:0001476	78.24	silver quality
leukocyte	CL:0000738	78.15	gold quality
monocyte	CL:0000576	77.90	gold quality
colonic epithelium	UBERON:0000397	77.73	gold quality
ganglionic eminence	UBERON:0004023	77.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.50	gold quality
bone marrow cell	CL:0002092	76.38	gold quality
stromal cell of endometrium	CL:0002255	76.27	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	76.22	silver quality
muscle of leg	UBERON:0001383	76.06	gold quality
epithelium of mammary gland	UBERON:0003244	75.90	gold quality
gastrocnemius	UBERON:0001388	75.87	gold quality
mammary duct	UBERON:0001765	75.80	gold quality
islet of Langerhans	UBERON:0000006	75.65	gold quality
quadriceps femoris	UBERON:0001377	75.63	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.53

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2523.1	ZNF689	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605530

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

89 targeting ZNF689, 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-3646	100.00	73.56	5283
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3662	99.99	73.82	5684
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6755-5P	99.95	65.59	464
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-MIR-300	99.92	71.76	2856
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767

Literature-anchored findings (GeneRIF, showing 5)

• TIPUH1 conferred anchorage independent growth and its knockdown in HCCs resulted in their growth inhibition. Interacts with TIF1beta, hnRNPU, hnRNPF, Nucleolin. May play a role in hepatocarcinogenesis by regulating transcription and/or RNA processing. (PMID:16568080)
• overexpressed TIPUH1 may play a role in hepatocarcinogenesis by regulating transcription and/or RNA processing of growth control genes (PMID:16568080)
• The results indicate that ZNF689 blocks pro-apoptotic signaling by suppressing the Bak/Bax/Bid pathway, resulting in the progression of liver cancer and resistance to 5-FU. ZNF689 may be a promising chemotherapeutic target against liver cancer. (PMID:21624362)
• A 3-Gene Random Forest Model to Diagnose Non-obstructive Azoospermia Based on Transcription Factor-Related Henes. (PMID:35715550)
• ZNF689 deficiency promotes intratumor heterogeneity and immunotherapy resistance in triple-negative breast cancer. (PMID:38168642)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf646	ENSDARG00000061424
danio_rerio	si:dkey-89b17.4	ENSDARG00000075545
danio_rerio	zgc:66472	ENSDARG00000075916
danio_rerio	si:ch211-148l7.4	ENSDARG00000094469
danio_rerio	znf576.1	ENSDARG00000097819
mus_musculus	Zfp689	ENSMUSG00000048921
rattus_norvegicus	Zfp689	ENSRNOG00000066277
drosophila_melanogaster	az2	FBGN0025185
drosophila_melanogaster	CG2129	FBGN0030008
drosophila_melanogaster	CG1602	FBGN0033186
drosophila_melanogaster	CG18011	FBGN0033491
drosophila_melanogaster	CG12942	FBGN0033569
drosophila_melanogaster	indra	FBGN0035213
drosophila_melanogaster	CG30020	FBGN0050020
drosophila_melanogaster	mld	FBGN0263490
caenorhabditis_elegans	ztf-15	WBGENE00011066
caenorhabditis_elegans		WBGENE00015649

Paralogs (36): ZNF302 (ENSG00000089335), ZNF184 (ENSG00000096654), CTCF (ENSG00000102974), ZNF574 (ENSG00000105732), ZBTB24 (ENSG00000112365), ZNF142 (ENSG00000115568), CTCFL (ENSG00000124092), ZNF473 (ENSG00000142528), ZNF827 (ENSG00000151612), ZNF208 (ENSG00000160321), ZNF91 (ENSG00000167232), ZNF526 (ENSG00000167625), ZNF764 (ENSG00000169951), ZNF747 (ENSG00000169955), ZNF282 (ENSG00000170265), ZNF160 (ENSG00000170949), ZNF497 (ENSG00000174586), ZBTB34 (ENSG00000177125), ZNF771 (ENSG00000179965), ZNF48 (ENSG00000180035), ZNF594 (ENSG00000180626), ZBTB37 (ENSG00000185278), ZFP92 (ENSG00000189420), ZNF107 (ENSG00000196247), ZNF729 (ENSG00000196350), ZNF569 (ENSG00000196437), ZNF420 (ENSG00000197050), ZNF785 (ENSG00000197162), ZNF665 (ENSG00000197497), ZNF181 (ENSG00000197841), ZNF347 (ENSG00000197937), ZNF84 (ENSG00000198040), ZBTB48 (ENSG00000204859), ZNF845 (ENSG00000213799), ZNF99 (ENSG00000213973), ZNF688 (ENSG00000229809)

Protein

Protein identifiers

Transcriptional regulator SEHBP — C0HLU2 (reviewed: C0HLU2, Q96CS4)

Alternative names: Short ORF-encoded histone-binding protein, ZNF689 upstream open reading frame protein

All UniProt accessions (1): Q96CS4

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in transcription regulation.

Subunit / interactions. Interacts with histone H2B. Also interacts with chromatin-binding proteins HMGN1 and HMGN3.

Subcellular location. Nucleus. Cytoplasm.

Miscellaneous. Encoded in the 5’-untranslated region (5’-UTR) of ZNF689.

RefSeq proteins (1): NP_612456* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR054150	SEHBP	Family
IPR001909	KRAB	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF01352, PF21978

UniProt features (20 total): zinc finger region 12, chain 2, region of interest 2, compositionally biased region 2, domain 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-C0HLU2-F1	47.42	0.00
AF-Q96CS4-F1	75.02	0.10

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 (1): 455

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 115 (showing top): ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, YY1_02, chr16p11, NRF2_01, HOWLIN_CITED1_TARGETS_1_UP, RAAGNYNNCTTY_UNKNOWN, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOMF_HISTONE_BINDING, STAT5A_02, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, CDPCR1_01, PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_7, CDP_02, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ASH1L_TARGET_GENES

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), skeletal muscle cell differentiation (GO:0035914), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): histone binding (GO:0042393), 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 (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
skeletal muscle tissue development	1
cell differentiation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein binding	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
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ZNF689	TRIM28	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0QND3, A1V7D6, A2S8D5, A3MS21, A3N476, A3NPX0, A5VQK8, B0RS40, B2JJR9, B2T7U2, B7GPF6, C0HLU2, C1CZW1, C1DNF8, O28696, O29555, P03851, P0A179, P0A180, P9WKY4, P9WKY5, Q0ICH4, Q0VDD5, Q12484, Q13SH3, Q1AR60, Q2K856, Q2P2E2, Q2STL9, Q2Y5A7, Q2YQ05, Q30YQ4, Q3BAI2, Q3BSH4, Q3JXI4, Q48BF1, Q4JSC3, Q4UVK1, Q4ZL10, Q57D63

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

594 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30605444:CTTT:C	acceptor_gain	1.0000
16:30605447:TCTAT:T	acceptor_loss	1.0000
16:30605448:C:CC	acceptor_gain	1.0000
16:30609521:TCACT:T	donor_loss	1.0000
16:30609522:CACTT:C	donor_loss	1.0000
16:30609523:A:AC	donor_gain	1.0000
16:30609523:A:C	donor_loss	1.0000
16:30609523:ACTT:A	donor_gain	1.0000
16:30609524:C:CG	donor_gain	1.0000
16:30609524:C:G	donor_loss	1.0000
16:30609524:CT:C	donor_gain	1.0000
16:30609524:CTT:C	donor_gain	1.0000
16:30609524:CTTC:C	donor_gain	1.0000
16:30609524:CTTCT:C	donor_gain	1.0000
16:30609526:T:TA	donor_gain	1.0000
16:30609635:CACC:C	acceptor_gain	1.0000
16:30605445:TTT:T	acceptor_gain	0.9900
16:30605446:TT:T	acceptor_gain	0.9900
16:30605450:A:C	acceptor_gain	0.9900
16:30609519:ACTC:A	donor_loss	0.9900
16:30609636:ACC:A	acceptor_gain	0.9900
16:30609637:CC:C	acceptor_gain	0.9900
16:30609637:CCC:C	acceptor_gain	0.9900
16:30609638:CC:C	acceptor_gain	0.9900
16:30609639:C:CC	acceptor_gain	0.9900
16:30609639:CT:C	acceptor_loss	0.9900
16:30609768:C:CA	donor_gain	0.9900
16:30609776:ACAC:A	donor_gain	0.9900
16:30609777:CACC:C	donor_gain	0.9900
16:30609779:C:CA	donor_gain	0.9900

AlphaMissense

3243 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30604453:A:C	F438L	0.998
16:30604453:A:T	F438L	0.998
16:30604455:A:G	F438L	0.998
16:30604705:G:C	F354L	0.998
16:30604705:G:T	F354L	0.998
16:30604707:A:G	F354L	0.998
16:30604957:G:C	F270L	0.998
16:30604957:G:T	F270L	0.998
16:30604959:A:G	F270L	0.998
16:30604621:G:C	F382L	0.997
16:30604621:G:T	F382L	0.997
16:30604623:A:G	F382L	0.997
16:30604789:G:C	F326L	0.997
16:30604789:G:T	F326L	0.997
16:30604791:A:G	F326L	0.997
16:30604873:G:C	F298L	0.997
16:30604873:G:T	F298L	0.997
16:30604875:A:G	F298L	0.997
16:30605125:G:C	F214L	0.997
16:30605125:G:T	F214L	0.997
16:30605127:A:G	F214L	0.997
16:30604369:G:C	F466L	0.996
16:30604369:G:T	F466L	0.996
16:30604371:A:G	F466L	0.996
16:30605014:G:C	H251Q	0.996
16:30605014:G:T	H251Q	0.996
16:30605041:G:C	F242L	0.996
16:30605041:G:T	F242L	0.996
16:30605043:A:G	F242L	0.996
16:30604537:A:C	F410L	0.995

dbSNP variants (sampled 300 via entrez): RS1000208497 (16:30607177 A>C,G), RS1000303067 (16:30607352 G>A), RS1001264920 (16:30602535 A>C), RS1001490718 (16:30608378 A>C), RS1001711275 (16:30608704 G>C), RS1002262192 (16:30603228 T>C), RS1002545356 (16:30610135 A>G), RS1002706857 (16:30602912 G>T), RS1003180796 (16:30610419 T>TC), RS1003214861 (16:30602454 T>G), RS1003773078 (16:30611945 T>A,C), RS1003960296 (16:30611569 T>G), RS1004049948 (16:30603731 A>C,G), RS1004568935 (16:30603291 G>A), RS1004663829 (16:30603658 A>G)

Disease associations

OMIM: gene MIM:618033 | 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
GCST006979_654	Heel bone mineral density	9.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

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	affects expression, decreases expression	4
(+)-JQ1 compound	decreases expression	3
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
urushiol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, affects cotreatment	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression, affects cotreatment	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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