ZNF140

Summary

ZNF140 (zinc finger protein 140, HGNC:12925) is a protein-coding gene on chromosome 12q24.33, encoding Zinc finger protein 140 (P52738). May be involved in transcriptional regulation as a repressor.

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 7699 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_003440

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12925
Approved symbol	ZNF140
Name	zinc finger protein 140
Location	12q24.33
Locus type	gene with protein product
Status	Approved
Aliases	pHZ-39
Ensembl gene	ENSG00000196387
Ensembl biotype	protein_coding
OMIM	604082
Entrez	7699

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000319849, ENST00000355557, ENST00000356456, ENST00000392041, ENST00000412146, ENST00000429434, ENST00000440550, ENST00000440984, ENST00000536790, ENST00000544426, ENST00000880216, ENST00000880217, ENST00000880218

RefSeq mRNA: 4 — MANE Select: NM_003440 NM_001300776, NM_001300777, NM_001300778, NM_003440

CCDS: CCDS73550, CCDS9282

Canonical transcript exons

ENST00000355557 — 5 exons

Exon	Start	End
ENSE00001359753	133080923	133081072
ENSE00002321298	133105510	133107428
ENSE00003493554	133081273	133081329
ENSE00003718943	133083466	133083561
ENSE00003741905	133083103	133083229

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 89.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1837 / max 68.3181, expressed in 1770 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128857	7.4004	1747
128856	1.7833	1174

Top tissues by expression

284 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	89.62	gold quality
calcaneal tendon	UBERON:0003701	89.46	gold quality
ganglionic eminence	UBERON:0004023	89.06	gold quality
cortical plate	UBERON:0005343	88.57	gold quality
ventricular zone	UBERON:0003053	87.73	gold quality
adenohypophysis	UBERON:0002196	87.40	gold quality
right uterine tube	UBERON:0001302	86.84	gold quality
left ovary	UBERON:0002119	86.37	gold quality
body of pancreas	UBERON:0001150	86.27	gold quality
left lobe of thyroid gland	UBERON:0001120	86.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.20	gold quality
right lobe of thyroid gland	UBERON:0001119	86.09	gold quality
thyroid gland	UBERON:0002046	86.03	gold quality
pituitary gland	UBERON:0000007	85.88	gold quality
right ovary	UBERON:0002118	85.73	gold quality
adrenal tissue	UBERON:0018303	85.45	gold quality
ovary	UBERON:0000992	85.42	gold quality
islet of Langerhans	UBERON:0000006	85.18	gold quality
pancreas	UBERON:0001264	84.90	gold quality
cerebellar hemisphere	UBERON:0002245	84.79	gold quality
body of uterus	UBERON:0009853	84.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.68	gold quality
left uterine tube	UBERON:0001303	84.61	gold quality
cerebellar cortex	UBERON:0002129	84.59	gold quality
blood vessel layer	UBERON:0004797	84.59	gold quality
oocyte	CL:0000023	84.16	gold quality
right adrenal gland cortex	UBERON:0035827	84.12	gold quality
right adrenal gland	UBERON:0001233	84.03	gold quality
endocervix	UBERON:0000458	83.99	gold quality
vagina	UBERON:0000996	83.98	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-110499	no	146.90
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
FCGR3B	Repression

JASPAR motifs

Motif	Name	Family
MA1589.1	ZNF140	More than 3 adjacent zinc fingers
MA1589.2	ZNF140	More than 3 adjacent zinc fingers
MA1589.3	ZNF140	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:28473536

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

78 targeting ZNF140, 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-4262	100.00	73.26	3931
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3119	99.92	71.34	2390

Cross-species orthologs

0 orthologs

Paralogs (176): ZNF195 (ENSG00000005801), ZNF112 (ENSG00000062370), ZNF275 (ENSG00000063587), ZNF37A (ENSG00000075407), ZNF510 (ENSG00000081386), ZNF506 (ENSG00000081665), ZNF268 (ENSG00000090612), MZF1 (ENSG00000099326), ZNF629 (ENSG00000102870), ZNF175 (ENSG00000105497), ZNF85 (ENSG00000105750), ZFP30 (ENSG00000120784), ZNF45 (ENSG00000124459), ZNF391 (ENSG00000124613), ZNF436 (ENSG00000125945), ZNF484 (ENSG00000127081), ZNF835 (ENSG00000127903), ZNF780B (ENSG00000128000), ZSCAN10 (ENSG00000130182), ZNF317 (ENSG00000130803), ZNF331 (ENSG00000130844), ZNF227 (ENSG00000131115), ZNF141 (ENSG00000131127), ZNF132 (ENSG00000131849), ZNF189 (ENSG00000136870), ZIM3 (ENSG00000141946), ZFP14 (ENSG00000142065), ZNF514 (ENSG00000144026), ZNF300 (ENSG00000145908), RBAK (ENSG00000146587), ZNF157 (ENSG00000147117), ZNF182 (ENSG00000147118), ZNF41 (ENSG00000147124), ZNF7 (ENSG00000147789), ZNF117 (ENSG00000152926), ZNF221 (ENSG00000159905), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631)

Protein

Protein identifiers

Zinc finger protein 140 — P52738 (reviewed: P52738)

All UniProt accessions (8): P52738, F5GX08, F5H3Z2, F5H4I1, F5H644, F8WAF8, I3L0D9, I3L0I7

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation as a repressor.

Subcellular location. Nucleus.

Tissue specificity. Seems ubiquitous. Seen in the heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P52738-1	1	yes
P52738-2	2

RefSeq proteins (4): NP_001287705, NP_001287706, NP_001287707, NP_003431* (*=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
IPR050527

Pfam: PF00096, PF01352, PF13912

UniProt features (15 total): zinc finger region 10, chain 1, domain 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52738-F1	68.78	0.08

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 90 (showing top): DODD_NASOPHARYNGEAL_CARCINOMA_UP, chr12q24, WIKMAN_ASBESTOS_LUNG_CANCER_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, OKUMURA_INFLAMMATORY_RESPONSE_LPS, HIRSCH_CELLULAR_TRANSFORMATION_SIGNATURE_UP, GREGORY_SYNTHETIC_LETHAL_WITH_IMATINIB, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, LTE2_UP.V1_DN, MEK_UP.V1_DN, GOMF_DNA_BINDING_TRANSCRIPTION_REPRESSOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, CBX7_TARGET_GENES, NFE2L1_TARGET_GENES

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (9): 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 transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), 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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transition metal ion binding	1
DNA 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

508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF140	LGALS4	P56470	549
ZNF140	SNRNP35	Q16560	507
ZNF140	EPHB2	P29323	366
ZNF140	MSH6	P52701	353
ZNF140	MSH3	P20585	353
ZNF140	DHRS13	Q6UX07	349
ZNF140	KANSL1L	A0AUZ9	348
ZNF140	TDRD10	Q5VZ19	324
ZNF140	TLNRD1	Q9H1K6	323
ZNF140	CCDC7	Q96M83	320
ZNF140	XAGE2	Q96GT9	315
ZNF140	E7ERQ6	E7ERQ6	305
ZNF140	EPHB1	P54762	303
ZNF140	NOC4L	Q9BVI4	296
ZNF140	ALKBH4	Q9NXW9	288

IntAct

15 interactions, top by confidence:

A	B	Type	Score
TEPSIN	AP4M1	psi-mi:“MI:0914”(association)	0.700
CABP2	ZNF140	psi-mi:“MI:0915”(physical association)	0.560
ZNF140	CEP70	psi-mi:“MI:0915”(physical association)	0.560
ZNF140	ARMC7	psi-mi:“MI:0915”(physical association)	0.560
ZNF140	CABP2	psi-mi:“MI:0915”(physical association)	0.560
WDR83	SH2B2	psi-mi:“MI:0914”(association)	0.530
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
WDR83	PIKFYVE	psi-mi:“MI:0914”(association)	0.350
ZNF140	CEP70	psi-mi:“MI:0915”(physical association)	0.000
ARMC7	ZNF140	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): ZNF140 (Affinity Capture-MS), ZNF140 (Biochemical Activity), ZNF140 (Affinity Capture-MS), ZNF140 (Two-hybrid), ZNF140 (Two-hybrid), ZNF140 (Two-hybrid), ZNF140 (Affinity Capture-MS), ZNF140 (Affinity Capture-MS), ZNF140 (Affinity Capture-MS), HMGB1 (Cross-Linking-MS (XL-MS)), ZNF140 (Affinity Capture-MS), TRIM28 (Reconstituted Complex)

ESM2 similar proteins: A0A1W2PQL4, A0JPL0, A2RRD8, A6NHJ4, A6NP11, B4DX44, O75346, O95780, P0CB33, P21506, P51508, P52738, Q0D2J5, Q0VGE8, Q12901, Q13360, Q14593, Q15973, Q2M218, Q2M3X9, Q2VY69, Q3SXZ3, Q5HY98, Q5RCJ2, Q5VIY5, Q6J6I6, Q7L2R6, Q86XU0, Q86Y25, Q8IW36, Q8IYN0, Q8IYX0, Q8N782, Q8N883, Q8N9Z0, Q8NDP4, Q95K49, Q969W8, Q96H40, Q96N58

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

1 interactions.

A	Effect	B	Mechanism
ZNF140	“down-regulates quantity by repression”	FCGR3B	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

906 predictions. Top by Δscore:

Variant	Effect	Δscore
12:133083101:AGG:A	acceptor_gain	1.0000
12:133083102:GGG:G	acceptor_gain	1.0000
12:133105508:A:AG	acceptor_gain	1.0000
12:133105509:G:GG	acceptor_gain	1.0000
12:133081069:T:G	donor_gain	0.9900
12:133083537:G:T	donor_gain	0.9900
12:133105506:TCA:T	acceptor_loss	0.9900
12:133105508:A:C	acceptor_loss	0.9900
12:133081033:A:T	donor_gain	0.9800
12:133083097:TTTCA:T	acceptor_loss	0.9800
12:133083098:TTCA:T	acceptor_loss	0.9800
12:133083099:TCA:T	acceptor_loss	0.9800
12:133083100:CA:C	acceptor_loss	0.9800
12:133083101:A:G	acceptor_loss	0.9800
12:133083102:G:GA	acceptor_loss	0.9800
12:133083228:GG:G	donor_gain	0.9800
12:133083229:GG:G	donor_gain	0.9800
12:133083230:G:GA	donor_loss	0.9800
12:133083231:TAA:T	donor_loss	0.9800
12:133093503:GTT:G	donor_gain	0.9800
12:133100973:A:G	acceptor_gain	0.9800
12:133081045:A:T	donor_gain	0.9700
12:133083101:A:AG	acceptor_gain	0.9700
12:133083102:G:GG	acceptor_gain	0.9700
12:133083225:ACTGG:A	donor_gain	0.9700
12:133083227:TGG:T	donor_gain	0.9700
12:133083228:GGG:G	donor_gain	0.9700
12:133083230:G:GG	donor_gain	0.9700
12:133083232:AAGTA:A	donor_loss	0.9700
12:133081044:G:GT	donor_gain	0.9600

AlphaMissense

3038 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:133106037:T:C	F254L	0.997
12:133106039:T:A	F254L	0.997
12:133106039:T:G	F254L	0.997
12:133105869:T:C	F198L	0.996
12:133105871:T:A	F198L	0.996
12:133105871:T:G	F198L	0.996
12:133106289:T:C	F338L	0.996
12:133106291:C:A	F338L	0.996
12:133106291:C:G	F338L	0.996
12:133106457:T:C	F394L	0.995
12:133106459:C:A	F394L	0.995
12:133106459:C:G	F394L	0.995
12:133106205:T:C	F310L	0.994
12:133106207:T:A	F310L	0.994
12:133106207:T:G	F310L	0.994
12:133106541:T:C	F422L	0.994
12:133106543:C:A	F422L	0.994
12:133106543:C:G	F422L	0.994
12:133105953:T:C	F226L	0.993
12:133105955:C:A	F226L	0.993
12:133105955:C:G	F226L	0.993
12:133106121:T:C	F282L	0.993
12:133106123:T:A	F282L	0.993
12:133106123:T:G	F282L	0.993
12:133106044:G:C	R256P	0.992
12:133106056:T:C	L260P	0.991
12:133106373:T:C	F366L	0.991
12:133106375:C:A	F366L	0.991
12:133106375:C:G	F366L	0.991
12:133106140:T:C	L288P	0.990

dbSNP variants (sampled 300 via entrez): RS1000150634 (12:133079992 A>G), RS1000182272 (12:133079679 C>T), RS1000189625 (12:133104237 A>G), RS1000261700 (12:133107249 A>T), RS1000314593 (12:133106947 C>A,T), RS1000332757 (12:133107629 C>T), RS1000499975 (12:133106968 A>G), RS1000504499 (12:133090819 A>C,G), RS1000514980 (12:133093827 T>A), RS1000535529 (12:133090790 A>C,G,T), RS1000572330 (12:133103378 T>A), RS1000672524 (12:133085859 A>T), RS1000867959 (12:133097686 C>T), RS1000937849 (12:133097517 C>G,T), RS1000977796 (12:133107272 A>G)

Disease associations

OMIM: gene MIM:604082 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005580_126	Intraocular pressure	4.000000e-08
GCST010002_179	Refractive error	1.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Valproic Acid	affects expression, decreases expression, increases expression	4
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression	1
Asbestos	affects expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Oxazolone	increases expression	1
Oxygen	decreases expression	1
Rotenone	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Copper Sulfate	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_XW07	HEK293 eGFP-ZNF140	Transformed cell line	Female

Clinical trials (associated diseases)

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