ZNF667

Summary

ZNF667 (zinc finger protein 667, HGNC:28854) is a protein-coding gene on chromosome 19q13.43, encoding Zinc finger protein 667 (Q5HYK9). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus.

Source: NCBI Gene 63934 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_001321356

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28854
Approved symbol	ZNF667
Name	zinc finger protein 667
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14011
Ensembl gene	ENSG00000198046
Ensembl biotype	protein_coding
OMIM	611024
Entrez	63934

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 30 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000292069, ENST00000504904, ENST00000587555, ENST00000589652, ENST00000589946, ENST00000591790, ENST00000592189, ENST00000909113, ENST00000909114, ENST00000909115, ENST00000909116, ENST00000909117, ENST00000909118, ENST00000909119, ENST00000909120, ENST00000930969, ENST00000930970, ENST00000930971, ENST00000930972, ENST00000930973, ENST00000930974, ENST00000967614, ENST00000967615, ENST00000967616, ENST00000967617, ENST00000967618, ENST00000967619, ENST00000967620, ENST00000967621, ENST00000967622, ENST00000967623, ENST00000967624

RefSeq mRNA: 3 — MANE Select: NM_001321356 NM_001321355, NM_001321356, NM_022103

CCDS: CCDS12944

Canonical transcript exons

ENST00000504904 — 7 exons

Exon	Start	End
ENSE00002083705	56471699	56472187
ENSE00002296774	56474012	56474124
ENSE00002968071	56477272	56477345
ENSE00003145221	56460689	56460815
ENSE00003527636	56462338	56462429
ENSE00003785474	56458155	56458247
ENSE00003842112	56439329	56442741

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 89.81.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1413 / max 137.5056, expressed in 749 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182882	1.6925	634
182883	0.4488	230

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	89.81	gold quality
middle temporal gyrus	UBERON:0002771	89.60	gold quality
pituitary gland	UBERON:0000007	89.17	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.50	gold quality
adenohypophysis	UBERON:0002196	87.37	gold quality
cortical plate	UBERON:0005343	87.07	gold quality
entorhinal cortex	UBERON:0002728	86.93	gold quality
substantia nigra pars compacta	UBERON:0001965	86.41	gold quality
nucleus accumbens	UBERON:0001882	86.33	gold quality
primary visual cortex	UBERON:0002436	86.32	gold quality
lateral globus pallidus	UBERON:0002476	85.31	gold quality
parietal lobe	UBERON:0001872	84.80	gold quality
superior frontal gyrus	UBERON:0002661	84.52	gold quality
postcentral gyrus	UBERON:0002581	84.47	gold quality
occipital lobe	UBERON:0002021	84.39	gold quality
right frontal lobe	UBERON:0002810	84.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.11	gold quality
superior vestibular nucleus	UBERON:0007227	84.04	gold quality
substantia nigra pars reticulata	UBERON:0001966	83.93	gold quality
corpus callosum	UBERON:0002336	83.69	gold quality
pons	UBERON:0000988	83.68	gold quality
Ammon’s horn	UBERON:0001954	83.68	gold quality
forebrain	UBERON:0001890	83.64	gold quality
frontal cortex	UBERON:0001870	83.63	gold quality
cerebral cortex	UBERON:0000956	83.47	gold quality
telencephalon	UBERON:0001893	83.46	gold quality
neocortex	UBERON:0001950	83.41	gold quality
caudate nucleus	UBERON:0001873	83.36	gold quality
temporal lobe	UBERON:0001871	83.28	gold quality
prefrontal cortex	UBERON:0000451	83.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
BAX
ZNF667

JASPAR motifs

Motif	Name	Family
MA1984.1	ZNF667	More than 3 adjacent zinc fingers
MA1984.2	ZNF667	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:27852650

Upstream regulators (CollecTRI, top): CREB1, HIF1A, ZNF667

miRNA regulators (miRDB)

60 targeting ZNF667, 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-4776-3P	100.00	68.73	1340
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669

Literature-anchored findings (GeneRIF, showing 6)

• ZNF667 promote the cell proliferation, invasion and migration mainly via interference expression of Bcl-2 and BAX. (PMID:28472789)
• ZNF667-AS1 and ZNF667 are both down-regulated by hypermethylation, and they serve as tumor suppressor genes in LSCC. ZNF667-AS1 regulates the expression of ZNF667 in cis. (PMID:30684967)
• Aberrant hypermethylation-mediated downregulation of antisense lncRNA ZNF667-AS1 and its sense gene ZNF667 correlate with progression and prognosis of esophageal squamous cell carcinoma. (PMID:31804468)
• Down-regulation of MIPU1 can promote apoptosis while inhibit the proliferation, invasion, and migration of U251 cells (PMID:32386033)
• MicroRNA-23b-3p participates in steroid-induced osteonecrosis of the femoral head by suppressing ZNF667 expression. (PMID:32730776)
• ZNF667 facilitates angiogenesis after myocardial ischemia through transcriptional regulation of VASH1 and Wnt signaling pathway. (PMID:36043524)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf574	ENSDARG00000087074
mus_musculus	Zfp667	ENSMUSG00000054893
rattus_norvegicus	Zfp667	ENSRNOG00000033906
drosophila_melanogaster	CG11902	FBGN0028647
drosophila_melanogaster	CG11696	FBGN0030314
drosophila_melanogaster	CG10631	FBGN0032817

Paralogs (7): ZNF671 (ENSG00000083814), ZNF710 (ENSG00000140548), ZNF212 (ENSG00000170260), ZNF366 (ENSG00000178175), ZNF662 (ENSG00000182983), ZNF783 (ENSG00000204946), ZNF865 (ENSG00000261221)

Protein

Protein identifiers

Zinc finger protein 667 — Q5HYK9 (reviewed: Q5HYK9)

All UniProt accessions (5): Q5HYK9, K7EIE0, K7EQ15, K7ERY5, M0QX02

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 (3): NP_001308284, NP_001308285, NP_071386 (=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 (25 total): zinc finger region 15, sequence variant 3, sequence conflict 3, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5HYK9-F1	70.29	0.12

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 88 (showing top): MODULE_503, MODULE_195, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, MODULE_147, MODULE_356, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, DODD_NASOPHARYNGEAL_CARCINOMA_DN, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, BILD_MYC_ONCOGENIC_SIGNATURE, FIGUEROA_AML_METHYLATION_CLUSTER_1_UP, FIGUEROA_AML_METHYLATION_CLUSTER_2_UP, FIGUEROA_AML_METHYLATION_CLUSTER_3_UP, FIGUEROA_AML_METHYLATION_CLUSTER_4_UP, FIGUEROA_AML_METHYLATION_CLUSTER_5_UP, FIGUEROA_AML_METHYLATION_CLUSTER_6_UP

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of biosynthetic process (GO:0009891), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), 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
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
biosynthetic process	1
regulation of biosynthetic process	1
positive regulation of metabolic process	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF667	SLFN12	Q8IYM2	447
ZNF667	VPS53	Q5VIR6	427
ZNF667	WDR7	Q9Y4E6	422
ZNF667	SORL1	Q92673	410
ZNF667	CTSF	Q9UBX1	400
ZNF667	PDE4D	Q08499	389
ZNF667	PLCB4	Q15147	388
ZNF667	SLC22A1	O15245	380
ZNF667	PCBP3	P57721	368
ZNF667	ZNF704	Q6ZNC4	367
ZNF667	ART1	P52961	362
ZNF667	CXCL5	P42830	353
ZNF667	TRIB3	Q96RU7	353
ZNF667	CACNA1A	P78510	353
ZNF667	EVC2	Q86UK5	351

IntAct

6 interactions, top by confidence:

A	B	Type	Score
KRTAP10-7	ZNF667	psi-mi:“MI:0915”(physical association)	0.560
ZNF667	VIM	psi-mi:“MI:0915”(physical association)	0.400
ZNF667	CDC37	psi-mi:“MI:0915”(physical association)	0.370
ZNF667	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): KRTAP10-7 (Two-hybrid), ZNF667 (Proximity Label-MS), ZNF667 (Affinity Capture-MS), ZNF667 (Proximity Label-MS), ZNF667 (Affinity Capture-MS), ZNF667 (Proximity Label-MS), ZNF667 (Two-hybrid), ZNF667 (Two-hybrid)

ESM2 similar proteins: A2RRD8, A6NHJ4, A6NK75, B4DU55, O75346, P0DPD5, P15621, P17030, P17039, P52737, Q0VGE8, Q14588, Q147U1, Q15928, Q2M3X9, Q3KNS6, Q494X3, Q4R6C2, Q5HYK9, Q5R5Q6, Q5R5S6, Q5REA0, Q5REK1, Q60585, Q61751, Q6ECI4, Q6P9Y7, Q6ZN19, Q6ZNA1, Q7Z3V5, Q86T29, Q86WZ6, Q8N141, Q8N7K0, Q8N9F8, Q8NA42, Q8NCK3, Q8NDQ6, Q8NEM1, Q8WV37

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

976 predictions. Top by Δscore:

Variant	Effect	Δscore
19:56460683:CCTTA:C	donor_loss	1.0000
19:56460684:CTT:C	donor_loss	1.0000
19:56460685:TTACC:T	donor_loss	1.0000
19:56460686:TA:T	donor_loss	1.0000
19:56460687:A:AC	donor_gain	1.0000
19:56460687:ACC:A	donor_loss	1.0000
19:56460688:C:A	donor_loss	1.0000
19:56460688:C:CC	donor_gain	1.0000
19:56460688:CCAAG:C	donor_gain	1.0000
19:56460816:C:CC	acceptor_gain	1.0000
19:56462425:CAGGG:C	acceptor_gain	1.0000
19:56462427:GGG:G	acceptor_gain	1.0000
19:56462430:C:CC	acceptor_gain	1.0000
19:56477267:CTTA:C	donor_loss	1.0000
19:56477268:TTAC:T	donor_loss	1.0000
19:56477269:TAC:T	donor_loss	1.0000
19:56477271:C:CG	donor_loss	1.0000
19:56458146:GTCAC:G	donor_loss	0.9900
19:56458147:TCACT:T	donor_loss	0.9900
19:56458148:CACT:C	donor_loss	0.9900
19:56458149:ACTCA:A	donor_loss	0.9900
19:56458150:CT:C	donor_loss	0.9900
19:56458151:TCA:T	donor_loss	0.9900
19:56458152:CACCA:C	donor_loss	0.9900
19:56458153:A:G	donor_loss	0.9900
19:56458154:C:A	donor_loss	0.9900
19:56460682:GCCTT:G	donor_loss	0.9900
19:56460687:AC:A	donor_gain	0.9900
19:56460688:CC:C	donor_gain	0.9900
19:56460688:CCA:C	donor_gain	0.9900

AlphaMissense

4075 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:56441286:A:G	L570P	0.999
19:56441303:A:C	F564L	0.999
19:56441303:A:T	F564L	0.999
19:56441305:A:G	F564L	0.999
19:56441387:A:C	F536L	0.999
19:56441387:A:T	F536L	0.999
19:56441389:A:G	F536L	0.999
19:56441471:G:C	F508L	0.999
19:56441471:G:T	F508L	0.999
19:56441473:A:G	F508L	0.999
19:56441555:G:C	F480L	0.999
19:56441555:G:T	F480L	0.999
19:56441557:A:G	F480L	0.999
19:56441276:A:C	H573Q	0.998
19:56441276:A:T	H573Q	0.998
19:56441278:G:C	H573D	0.998
19:56441274:T:G	Q574P	0.997
19:56441280:C:G	R572P	0.997
19:56441304:A:G	F564S	0.997
19:56441370:A:G	L542P	0.997
19:56441454:A:G	L514P	0.997
19:56441472:A:G	F508S	0.997
19:56441538:A:G	L486P	0.997
19:56441278:G:T	H573N	0.996
19:56441444:A:C	H517Q	0.996
19:56441444:A:T	H517Q	0.996
19:56441528:A:C	H489Q	0.996
19:56441528:A:T	H489Q	0.996
19:56441530:G:C	H489D	0.996
19:56441639:G:C	F452L	0.996

dbSNP variants (sampled 300 via entrez): RS1000034281 (19:56477642 A>C), RS1000115909 (19:56446837 C>T), RS1000136988 (19:56466522 G>C), RS1000188556 (19:56474402 C>G), RS1000247853 (19:56479955 C>A,G,T), RS1000254031 (19:56472527 C>T), RS1000722829 (19:56457403 C>T), RS1000810506 (19:56469246 C>A,T), RS1000854423 (19:56462697 C>A,G), RS1001102718 (19:56457017 C>G,T), RS1001129620 (19:56468609 G>A), RS1001273296 (19:56443801 A>G), RS1001407770 (19:56474742 T>C,G), RS1001448626 (19:56472480 G>C), RS1001531573 (19:56469527 C>T)

Disease associations

OMIM: gene MIM:611024 | 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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases expression	2
Nickel	decreases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases methylation	1
arsenite	decreases expression, increases methylation	1
tobacco tar	decreases expression, decreases reaction	1
diallyl disulfide	decreases expression, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Valproic Acid	increases expression	1
Aflatoxin B1	increases methylation	1
Particulate Matter	increases abundance, increases expression	1
Volatile Organic Compounds	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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