ZNF138

Summary

ZNF138 (zinc finger protein 138, HGNC:12922) is a protein-coding gene on chromosome 7q11.21, encoding Zinc finger protein 138 (P52744). May be involved in transcriptional regulation as a repressor.

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

Source: NCBI Gene 7697 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_001271639

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12922
Approved symbol	ZNF138
Name	zinc finger protein 138
Location	7q11.21
Locus type	gene with protein product
Status	Approved
Aliases	pHZ-32
Ensembl gene	ENSG00000197008
Ensembl biotype	protein_coding
OMIM	604080
Entrez	7697

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000307355, ENST00000359735, ENST00000430838, ENST00000437743, ENST00000440155, ENST00000440598, ENST00000494380

RefSeq mRNA: 11 — MANE Select: NM_001271639 NM_001160183, NM_001271637, NM_001271638, NM_001271639, NM_001271640, NM_001271649, NM_001367572, NM_001367574, NM_001367575, NM_001367577, NM_006524

CCDS: CCDS34645, CCDS55115, CCDS64659, CCDS64660, CCDS64661, CCDS75607

Canonical transcript exons

ENST00000307355 — 4 exons

Exon	Start	End
ENSE00001849210	64831451	64833680
ENSE00003600414	64794428	64794571
ENSE00003687201	64815576	64815653
ENSE00003733988	64814918	64815044

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 88.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.2663 / max 448.9475, expressed in 1737 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78816	17.0826	1714
78817	1.9856	739
78815	1.1042	608
204459	0.0940	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	88.96	gold quality
cortical plate	UBERON:0005343	87.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.27	gold quality
ventricular zone	UBERON:0003053	85.22	gold quality
adrenal tissue	UBERON:0018303	82.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.99	gold quality
corpus callosum	UBERON:0002336	80.80	gold quality
calcaneal tendon	UBERON:0003701	80.59	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.27	gold quality
Brodmann (1909) area 46	UBERON:0006483	79.78	gold quality
spinal cord	UBERON:0002240	78.94	gold quality
epithelium of nasopharynx	UBERON:0001951	78.67	gold quality
islet of Langerhans	UBERON:0000006	77.75	gold quality
skin of abdomen	UBERON:0001416	77.70	gold quality
substantia nigra	UBERON:0002038	77.01	gold quality
cerebellar vermis	UBERON:0004720	76.69	gold quality
lower esophagus mucosa	UBERON:0035834	76.47	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.44	gold quality
left adrenal gland	UBERON:0001234	76.42	gold quality
adrenal gland	UBERON:0002369	76.39	gold quality
prefrontal cortex	UBERON:0000451	76.27	gold quality
secondary oocyte	CL:0000655	76.20	gold quality
lymph node	UBERON:0000029	76.19	gold quality
rectum	UBERON:0001052	76.10	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.10	gold quality
tonsil	UBERON:0002372	76.06	gold quality
amygdala	UBERON:0001876	75.93	gold quality
right adrenal gland cortex	UBERON:0035827	75.92	gold quality
anterior cingulate cortex	UBERON:0009835	75.90	gold quality
sperm	CL:0000019	75.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting ZNF138, 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-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
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-6845-3P	99.94	66.88	1439
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942

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 138 — P52744 (reviewed: P52744)

All UniProt accessions (6): A0A0A0MRG3, A0A0A0MT90, C9JHF6, E7EWC5, P52744, J3QSS9

UniProt curated annotations — full annotation on UniProt →

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

Subcellular location. Nucleus.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P52744-1	1	yes
P52744-2	2
P52744-3	3

RefSeq proteins (10): NP_001153655, NP_001258566, NP_001258567, NP_001258568, NP_001258569, NP_001354501, NP_001354503, NP_001354504, NP_001354506, NP_006515 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF13912

UniProt features (14 total): zinc finger region 6, sequence conflict 3, splice variant 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52744-F1	68.84	0.24

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 98 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS, chr7q11, XU_GH1_AUTOCRINE_TARGETS_DN, TGGAAA_NFAT_Q4_01, HAMAI_APOPTOSIS_VIA_TRAIL_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, ZWANG_DOWN_BY_2ND_EGF_PULSE, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ASH1L_TARGET_GENES, CBX5_TARGET_GENES, CEBPZ_TARGET_GENES, CHAMP1_TARGET_GENES

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (6): 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), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), membrane (GO:0016020)

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
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	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
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

61 interactions, top by confidence:

A	B	Type	Score
DHPS	ZNF138	psi-mi:“MI:0915”(physical association)	0.560
	ZNF138	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	MDFI	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	TRIM41	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	ELOA2	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	KRTAP10-6	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	LHX6	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	BCCIP	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
MAPK9	ZNF138	psi-mi:“MI:0915”(physical association)	0.560
GRN	ZNF138	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	WFS1	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
HTT	ZNF138	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (25): ZNF138 (Two-hybrid), ZNF138 (Two-hybrid), TRIM41 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), ZBTB8A (Two-hybrid), ZNF138 (Two-hybrid), ZNF138 (Two-hybrid), ZNF138 (Two-hybrid), ZNF138 (Two-hybrid), ZNF138 (Two-hybrid), ZNF138 (Two-hybrid), ZNF138 (Two-hybrid), ZNF138 (Two-hybrid)

ESM2 similar proteins: A0A1W2PQL4, A0JPL0, A7MBI1, A8MUZ8, A8MWA4, B2RXC5, E7ETH6, E9Q8G5, O14628, P0CB33, P0CH99, P0CI00, P21506, P51508, P52744, Q02525, Q0D2J5, Q12901, Q13360, Q15973, Q2M218, Q2VY69, Q4R882, Q5FWF6, Q5HY98, Q5JVG8, Q6P280, Q6V9R5, Q6ZN11, Q6ZN79, Q86XU0, Q8IVC4, Q8IW36, Q8IYX0, Q8N587, Q8N782, Q8N859, Q8NB42, Q8NDP4, Q8NE65

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1308 predictions. Top by Δscore:

Variant	Effect	Δscore
7:64814993:A:T	donor_gain	1.0000
7:64815043:GG:G	donor_gain	1.0000
7:64815044:GG:G	donor_gain	1.0000
7:64815045:G:GG	donor_gain	1.0000
7:64815045:GT:G	donor_loss	1.0000
7:64815046:T:G	donor_loss	1.0000
7:64817334:GA:G	donor_gain	1.0000
7:64817336:G:GG	donor_gain	1.0000
7:64831074:GAT:G	donor_gain	1.0000
7:64831450:GCTCT:G	acceptor_gain	1.0000
7:64794537:C:G	donor_gain	0.9900
7:64794573:T:G	donor_loss	0.9900
7:64814906:C:CA	acceptor_gain	0.9900
7:64814912:TTTCA:T	acceptor_loss	0.9900
7:64814913:TTCA:T	acceptor_loss	0.9900
7:64814914:TCAGG:T	acceptor_loss	0.9900
7:64814915:CA:C	acceptor_loss	0.9900
7:64814916:A:AG	acceptor_gain	0.9900
7:64814916:AG:A	acceptor_gain	0.9900
7:64814916:AGG:A	acceptor_gain	0.9900
7:64814917:G:GG	acceptor_gain	0.9900
7:64814917:GG:G	acceptor_gain	0.9900
7:64814917:GGG:G	acceptor_gain	0.9900
7:64814917:GGGAC:G	acceptor_gain	0.9900
7:64815005:C:T	donor_gain	0.9900
7:64815047:G:GG	donor_loss	0.9900
7:64815554:A:G	acceptor_gain	0.9900
7:64815570:A:G	acceptor_gain	0.9900
7:64817329:TTACA:T	donor_gain	0.9900
7:64820218:A:AG	acceptor_gain	0.9900

AlphaMissense

2129 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000048354 (7:64807939 AT>A), RS1000064909 (7:64830597 A>G), RS1000079610 (7:64815318 C>T), RS1000148791 (7:64814087 C>T), RS1000181768 (7:64850312 C>T), RS1000210284 (7:64812385 C>T), RS1000226067 (7:64832297 C>A,T), RS1000283630 (7:64797753 CAA>C), RS1000332403 (7:64817809 A>T), RS1000373904 (7:64861323 G>C), RS1000412837 (7:64850121 T>C), RS1000585703 (7:64845530 A>G), RS1000633860 (7:64792743 G>T), RS1000653959 (7:64844130 G>A), RS1000671681 (7:64819111 G>T)

Disease associations

OMIM: gene MIM:604080 | 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

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
Cadmium Chloride	increases abundance, increases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	decreases expression	1
Sunitinib	decreases expression	1
Lycopene	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Cadmium	increases abundance, increases expression	1
Cisplatin	decreases expression	1
Clorgyline	increases expression	1
Coal	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression, increases abundance	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Valproic Acid	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_HD09	HEK293 eGFP-ZNF138	Transformed cell line	Female

Clinical trials (associated diseases)

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