ZNF675

Summary

ZNF675 (zinc finger protein 675, HGNC:30768) is a protein-coding gene on chromosome 19p12, encoding Zinc finger protein 675 (Q8TD23). May be involved in transcriptional regulation.

Enables ubiquitin protein ligase binding activity. Involved in negative regulation of osteoclast differentiation; negative regulation of signal transduction; and regulation of DNA-templated transcription. Located in nucleus and perinuclear region of cytoplasm.

Source: NCBI Gene 171392 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_138330

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30768
Approved symbol	ZNF675
Name	zinc finger protein 675
Location	19p12
Locus type	gene with protein product
Status	Approved
Aliases	TIZ, TBZF
Ensembl gene	ENSG00000197372
Ensembl biotype	protein_coding
OMIM	620090
Entrez	171392

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000359788, ENST00000596211, ENST00000597074, ENST00000599168, ENST00000599535, ENST00000600299, ENST00000600313, ENST00000601010, ENST00000601935, ENST00000913068

RefSeq mRNA: 1 — MANE Select: NM_138330 NM_138330

CCDS: CCDS32981

Canonical transcript exons

ENST00000359788 — 4 exons

Exon	Start	End
ENSE00001432517	23652801	23654706
ENSE00003094897	23687031	23687212
ENSE00003511745	23663032	23663158
ENSE00003685688	23662114	23662209

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 89.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5478 / max 133.5535, expressed in 1570 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180278	4.0871	1309
180279	3.0954	1143
180276	0.1512	60
180277	0.1361	45
208753	0.0780	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.27	gold quality
buccal mucosa cell	CL:0002336	89.09	gold quality
cortical plate	UBERON:0005343	88.81	gold quality
adrenal tissue	UBERON:0018303	86.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.89	gold quality
ganglionic eminence	UBERON:0004023	84.78	gold quality
ventricular zone	UBERON:0003053	83.01	gold quality
calcaneal tendon	UBERON:0003701	82.95	gold quality
rectum	UBERON:0001052	82.82	gold quality
sural nerve	UBERON:0015488	82.55	gold quality
skin of abdomen	UBERON:0001416	79.03	gold quality
islet of Langerhans	UBERON:0000006	78.90	gold quality
lower esophagus mucosa	UBERON:0035834	78.59	gold quality
granulocyte	CL:0000094	78.53	gold quality
right testis	UBERON:0004534	78.22	gold quality
leukocyte	CL:0000738	77.96	gold quality
monocyte	CL:0000576	77.88	gold quality
left testis	UBERON:0004533	77.86	gold quality
mononuclear cell	CL:0000842	77.63	gold quality
cerebellar hemisphere	UBERON:0002245	77.42	gold quality
cerebellar cortex	UBERON:0002129	77.35	gold quality
testis	UBERON:0000473	77.29	gold quality
prefrontal cortex	UBERON:0000451	77.24	gold quality
anterior cingulate cortex	UBERON:0009835	77.10	gold quality
cingulate cortex	UBERON:0003027	76.99	gold quality
right frontal lobe	UBERON:0002810	76.63	gold quality
vagina	UBERON:0000996	76.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.46	gold quality
esophagus mucosa	UBERON:0002469	75.76	gold quality
skin of leg	UBERON:0001511	75.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.72

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1714.1	ZNF675	More than 3 adjacent zinc fingers
MA1714.2	ZNF675	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:31427604

miRNA regulators (miRDB)

25 targeting ZNF675, 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-3925-3P	100.00	69.95	1237
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-3192-3P	98.62	65.80	970
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-192-3P	97.52	67.66	1001
HSA-MIR-6807-5P	97.51	64.25	1046
HSA-MIR-514A-3P	96.43	67.77	1048
HSA-MIR-514B-3P	96.43	67.77	1048
HSA-MIR-4315	94.78	64.86	112

Literature-anchored findings (GeneRIF, showing 2)

• the novel zinc finger protein TIZ may play a role during osteoclast differentiation by modulating TRAF6 signaling activity. (PMID:11751921)
• Emergence of the ZNF675 Gene During Primate Evolution-Influenced Human Neurodevelopment Through Changing HES1 Autoregulation. (PMID:38958676)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000099025

Paralogs (18): ZNF430 (ENSG00000118620), ZNF92 (ENSG00000146757), ZNF66 (ENSG00000160229), ZNF22 (ENSG00000165512), ZNF680 (ENSG00000173041), ZNF114 (ENSG00000178150), ZFP41 (ENSG00000181638), ZNF730 (ENSG00000183850), ZNF479 (ENSG00000185177), ZNF626 (ENSG00000188171), ZNF431 (ENSG00000196705), ZNF100 (ENSG00000197020), ZNF257 (ENSG00000197134), ZNF98 (ENSG00000197360), ZNF273 (ENSG00000198039), ZNF737 (ENSG00000237440), ZNF253 (ENSG00000256771), ZNF723 (ENSG00000268696)

Protein

Protein identifiers

Zinc finger protein 675 — Q8TD23 (reviewed: Q8TD23)

Alternative names: TRAF6-binding zinc finger protein, TRAF6-inhibitory zinc finger protein

All UniProt accessions (8): Q8TD23, M0QXM7, M0QXU1, M0R1W1, M0R1X5, M0R373, M0R3E4, M0R3G8

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation. May play a role during osteoclast differentiation by modulating TRAF6 signaling activity.

Subunit / interactions. Interacts with TRAF6.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_612203* (*=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

Pfam: PF00096, PF01352

UniProt features (27 total): zinc finger region 15, sequence conflict 7, sequence variant 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD23-F1	71.72	0.17

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 104 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_TUMOR_NECROSIS_FACTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_NEGATIVE_REGULATION_OF_HEMOPOIESIS, GOBP_JNK_CASCADE

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of cytokine-mediated signaling pathway (GO:0001960), regulation of DNA-templated transcription (GO:0006355), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), bone resorption (GO:0045453), negative regulation of osteoclast differentiation (GO:0045671), negative regulation of JNK cascade (GO:0046329), negative regulation of interleukin-1-mediated signaling pathway (GO:2000660)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), zinc ion binding (GO:0008270), ubiquitin protein ligase binding (GO:0031625), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), perinuclear region of cytoplasm (GO:0048471)

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
negative regulation of cytokine-mediated signaling pathway	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
regulation of cytokine-mediated signaling pathway	1
negative regulation of signal transduction	1
cytokine-mediated signaling pathway	1
negative regulation of response to cytokine stimulus	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
tissue homeostasis	1
bone remodeling	1
negative regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
JNK cascade	1
negative regulation of MAPK cascade	1
regulation of JNK cascade	1
interleukin-1-mediated signaling pathway	1
regulation of interleukin-1-mediated signaling pathway	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
nucleic acid binding	1
transition metal ion binding	1
ubiquitin-like protein ligase binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF675	ABHD12B	Q7Z5M8	413
ZNF675	GCM1	Q9NP62	328
ZNF675	AP3B2	Q13367	321
ZNF675	ZC2HC1A	Q96GY0	305
ZNF675	WHAMM	Q8TF30	300
ZNF675	ARGFX	A6NJG6	278
ZNF675	SERTAD3	Q9UJW9	259
ZNF675	MAP7D2	Q96T17	252
ZNF675	EPHX4	Q8IUS5	249
ZNF675	PHTF1	Q9UMS5	247
ZNF675	INTS1	Q8N201	241
ZNF675	ATXN1L	P0C7T5	233
ZNF675	TSPAN31	Q12999	228
ZNF675	IRAK1BP1	Q5VVH5	224
ZNF675	WBP11	Q9Y2W2	223
ZNF675	KCNK1	O00180	223

IntAct

11 interactions, top by confidence:

A	B	Type	Score
TRAF6	ZNF675	psi-mi:“MI:0915”(physical association)	0.540
ZNF675	TRAF6	psi-mi:“MI:0915”(physical association)	0.540
TRAF6	ZNF675	psi-mi:“MI:0403”(colocalization)	0.540
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
ZNF675	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ECE1	ZNF675	psi-mi:“MI:0915”(physical association)	0.370
ZNF675	LMO4	psi-mi:“MI:0915”(physical association)	0.370
HTT	ZNF675	psi-mi:“MI:0915”(physical association)	0.370
ZNF675	LDHC	psi-mi:“MI:0914”(association)	0.350

BioGRID (19): ZNF675 (Affinity Capture-MS), ZNF675 (Affinity Capture-RNA), KPRP (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), SIRT1 (Affinity Capture-MS), ZNF492 (Affinity Capture-MS), LDHC (Affinity Capture-MS), ZNF675 (Affinity Capture-MS), ZNF675 (Affinity Capture-Western), ZNF675 (Phenotypic Suppression), ZNF675 (Two-hybrid), TRAF6 (Reconstituted Complex), ZNF675 (Phenotypic Enhancement), ZNF675 (Phenotypic Suppression), ZNF675 (Phenotypic Suppression)

ESM2 similar proteins: A6NK75, A6NNF4, A6NP11, A8MTY0, A8MUV8, B4DXR9, C9JN71, O75346, O75373, O95780, P0CJ79, P0DKX0, P0DPD5, P17019, P17035, P35789, Q03923, Q03938, Q08AN1, Q14593, Q15928, Q3SXZ3, Q3ZCX4, Q5MCW4, Q5R9S5, Q5RER9, Q68DY1, Q6JLC9, Q6ZMV8, Q6ZN06, Q6ZN08, Q6ZNA1, Q76KX8, Q86T29, Q86V71, Q8IYN0, Q8N4W9, Q8N7M2, Q8NEM1, Q8TD23

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

876 predictions. Top by Δscore:

Variant	Effect	Δscore
19:23654702:CATTA:C	acceptor_gain	1.0000
19:23654703:ATTA:A	acceptor_gain	1.0000
19:23654704:TTA:T	acceptor_gain	1.0000
19:23654705:TA:T	acceptor_gain	1.0000
19:23654706:ACT:A	acceptor_loss	1.0000
19:23654707:C:CA	acceptor_loss	1.0000
19:23654707:C:CC	acceptor_gain	1.0000
19:23662110:TTACC:T	donor_loss	1.0000
19:23662111:TAC:T	donor_loss	1.0000
19:23662112:A:AC	donor_gain	1.0000
19:23662112:A:AG	donor_loss	1.0000
19:23662113:C:CC	donor_gain	1.0000
19:23662205:AATAC:A	acceptor_gain	1.0000
19:23662206:ATAC:A	acceptor_gain	1.0000
19:23662207:TAC:T	acceptor_gain	1.0000
19:23662208:AC:A	acceptor_gain	1.0000
19:23662209:CC:C	acceptor_gain	1.0000
19:23662209:CCTGT:C	acceptor_loss	1.0000
19:23662210:C:CC	acceptor_gain	1.0000
19:23662213:T:TC	acceptor_gain	1.0000
19:23662214:T:C	acceptor_gain	1.0000
19:23662215:T:C	acceptor_gain	1.0000
19:23662215:T:TC	acceptor_gain	1.0000
19:23662217:A:C	acceptor_gain	1.0000
19:23662218:T:C	acceptor_gain	1.0000
19:23662218:T:TC	acceptor_gain	1.0000
19:23663026:CCTTA:C	donor_loss	1.0000
19:23663027:CTTAC:C	donor_loss	1.0000
19:23663028:TTACC:T	donor_loss	1.0000
19:23663029:TA:T	donor_loss	1.0000

AlphaMissense

3786 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:23653382:A:C	F517L	0.989
19:23653382:A:T	F517L	0.989
19:23653384:A:G	F517L	0.989
19:23653886:A:C	F349L	0.988
19:23653886:A:T	F349L	0.988
19:23653888:A:G	F349L	0.988
19:23653550:A:C	F461L	0.987
19:23653550:A:T	F461L	0.987
19:23653552:A:G	F461L	0.987
19:23653634:A:C	F433L	0.986
19:23653634:A:T	F433L	0.986
19:23653636:A:G	F433L	0.986
19:23654054:A:C	F293L	0.986
19:23654054:A:T	F293L	0.986
19:23654056:A:G	F293L	0.986
19:23653970:A:C	F321L	0.985
19:23653970:A:T	F321L	0.985
19:23653972:A:G	F321L	0.985
19:23653802:A:C	F377L	0.984
19:23653802:A:T	F377L	0.984
19:23653804:A:G	F377L	0.984
19:23653466:A:C	F489L	0.982
19:23653466:A:T	F489L	0.982
19:23653468:A:G	F489L	0.982
19:23653718:A:C	F405L	0.979
19:23653718:A:T	F405L	0.979
19:23653720:A:G	F405L	0.979
19:23653298:A:C	F545L	0.976
19:23653298:A:T	F545L	0.976
19:23653300:A:G	F545L	0.976

dbSNP variants (sampled 300 via entrez): RS1000139349 (19:23686264 T>C), RS1000172260 (19:23686510 G>C), RS1000247142 (19:23666509 A>G), RS1000422710 (19:23672192 A>G), RS1000455222 (19:23672493 C>T), RS1000503530 (19:23687440 A>G), RS1000582729 (19:23681712 G>C), RS1000691458 (19:23654858 G>A,C,T), RS1000755876 (19:23673926 G>C), RS1000797587 (19:23677348 A>G), RS1000865521 (19:23671205 A>G), RS1000892487 (19:23677060 G>A,C), RS1000965137 (19:23667610 C>T), RS1001101124 (19:23681996 C>T), RS1001163318 (19:23661061 C>CTT)

Disease associations

OMIM: gene MIM:620090 | 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
GCST009391_1339	Metabolite levels	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010362	lysophosphatidylcholine 20:3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases expression	3
sodium arsenite	increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Formaldehyde	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
2-anisidine	decreases expression	1
triphenyl phosphate	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Benzethonium	decreases expression	1
Cisplatin	decreases expression	1
Coal	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Valproic Acid	decreases expression	1
Isotretinoin	decreases expression	1
Cadmium Chloride	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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