ZNF438

Summary

ZNF438 (zinc finger protein 438, HGNC:21029) is a protein-coding gene on chromosome 10p11.23, encoding Zinc finger protein 438 (Q7Z4V0). Isoform 1 acts as a transcriptional repressor.

Enables DNA-binding transcription factor activity. Involved in negative regulation of DNA-templated transcription. Located in cytosol and nucleoplasm.

Source: NCBI Gene 220929 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 141 total
• MANE Select transcript: NM_001143768

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21029
Approved symbol	ZNF438
Name	zinc finger protein 438
Location	10p11.23
Locus type	gene with protein product
Status	Approved
Aliases	bA330O11.1
Ensembl gene	ENSG00000183621
Ensembl biotype	protein_coding
OMIM	620749
Entrez	220929

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 42 protein_coding, 1 nonsense_mediated_decay

ENST00000331737, ENST00000361310, ENST00000375311, ENST00000413025, ENST00000436087, ENST00000442986, ENST00000452305, ENST00000538351, ENST00000609683, ENST00000885964, ENST00000885965, ENST00000885966, ENST00000885967, ENST00000885968, ENST00000885969, ENST00000885970, ENST00000885971, ENST00000885972, ENST00000885973, ENST00000885974, ENST00000885975, ENST00000885976, ENST00000885977, ENST00000885978, ENST00000885979, ENST00000885980, ENST00000885981, ENST00000916165, ENST00000916166, ENST00000945872, ENST00000945873, ENST00000945874, ENST00000945875, ENST00000945876, ENST00000945877, ENST00000945878, ENST00000945879, ENST00000945880, ENST00000945881, ENST00000945882, ENST00000945883, ENST00000945884, ENST00000945885

RefSeq mRNA: 10 — MANE Select: NM_001143768 NM_001143766, NM_001143767, NM_001143768, NM_001143769, NM_001143770, NM_001143771, NM_001387405, NM_001387411, NM_001387412, NM_182755

CCDS: CCDS44369, CCDS53504, CCDS7168

Canonical transcript exons

ENST00000436087 — 7 exons

Exon	Start	End
ENSE00001365983	30941575	30941651
ENSE00001380125	30908933	30909015
ENSE00001524163	30984369	30984426
ENSE00003474084	30848531	30850367
ENSE00003487529	30876998	30877065
ENSE00003967280	31031833	31031865
ENSE00003967281	30844632	30845573

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 91.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.8337 / max 336.0323, expressed in 1641 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108959	4.7874	1521
108957	3.4761	448
108956	1.2543	263
108960	0.4402	225
108961	0.3295	154
108955	0.2943	111
108958	0.1986	52
108949	0.0353	8
108950	0.0180	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	91.70	silver quality
monocyte	CL:0000576	90.41	gold quality
deltoid	UBERON:0001476	89.99	silver quality
leukocyte	CL:0000738	89.70	gold quality
calcaneal tendon	UBERON:0003701	88.78	gold quality
tendon	UBERON:0000043	87.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.89	gold quality
gastrocnemius	UBERON:0001388	87.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.65	gold quality
muscle of leg	UBERON:0001383	87.38	gold quality
tendon of biceps brachii	UBERON:0008188	87.27	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.56	gold quality
left ventricle myocardium	UBERON:0006566	86.52	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.33	gold quality
secondary oocyte	CL:0000655	85.87	gold quality
oocyte	CL:0000023	85.46	gold quality
saphenous vein	UBERON:0007318	85.23	gold quality
layer of synovial tissue	UBERON:0007616	85.23	gold quality
blood	UBERON:0000178	85.08	gold quality
apex of heart	UBERON:0002098	84.59	gold quality
skeletal muscle tissue	UBERON:0001134	84.35	gold quality
muscle tissue	UBERON:0002385	84.17	gold quality
biceps brachii	UBERON:0001507	83.75	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.70	gold quality
granulocyte	CL:0000094	83.63	gold quality
quadriceps femoris	UBERON:0001377	83.13	silver quality
pancreatic ductal cell	CL:0002079	83.09	silver quality
ascending aorta	UBERON:0001496	82.78	gold quality
thoracic aorta	UBERON:0001515	82.73	gold quality
ventricular zone	UBERON:0003053	82.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting ZNF438, 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-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-27B-5P	97.34	66.55	549

Literature-anchored findings (GeneRIF, showing 1)

• The transcriptional activity of ZNF438 was studied by transfecting recombinant pM-ZNF438 into mammalian cells. The subsequent analysis based on the duel luciferase assay system showed that ZNF438 was a transcriptional repressor. (PMID:17669267)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf438	ENSDARG00000061311
mus_musculus	Zfp438	ENSMUSG00000050945
rattus_norvegicus	Zfp438	ENSRNOG00000028329
caenorhabditis_elegans		WBGENE00005008
caenorhabditis_elegans		WBGENE00006827
caenorhabditis_elegans		WBGENE00011924
caenorhabditis_elegans		WBGENE00011925

Paralogs (2): ZBTB4 (ENSG00000174282), ZBTB38 (ENSG00000177311)

Protein

Protein identifiers

Zinc finger protein 438 — Q7Z4V0 (reviewed: Q7Z4V0)

All UniProt accessions (3): Q7Z4V0, Q5T427, V9GYJ1

UniProt curated annotations — full annotation on UniProt →

Function. Isoform 1 acts as a transcriptional repressor.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q7Z4V0-1	1	yes
Q7Z4V0-2	2
Q7Z4V0-3	3

RefSeq proteins (10): NP_001137238, NP_001137239, NP_001137240, NP_001137241, NP_001137242, NP_001137243, NP_001374334, NP_001374340, NP_001374341, NP_877432 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

UniProt features (18 total): zinc finger region 4, region of interest 4, compositionally biased region 3, sequence variant 3, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z4V0-F1	49.71	0.03

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 58 (showing top): ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, KONDO_PROSTATE_CANCER_HCP_WITH_H3K27ME3, MARSON_BOUND_BY_E2F4_UNSTIMULATED, chr10p11, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, DELACROIX_RARG_BOUND_MEF, DELACROIX_RAR_BOUND_ES, GSE13522_WT_VS_IFNAR_KO_SKING_T_CRUZI_Y_STRAIN_INF_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, CBX7_TARGET_GENES, NAB2_TARGET_GENES, TFEB_TARGET_GENES, ZNF10_TARGET_GENES, ZNF22_TARGET_GENES

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (7): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
cellular anatomical structure	2
transcription by RNA polymerase II	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

550 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF438	ZNF780A	O75290	567
ZNF438	ZNF546	Q86UE3	552
ZNF438	ZNF780B	Q9Y6R6	535
ZNF438	ZNF827	Q17R98	491
ZNF438	GARIN6	Q8NEG0	480
ZNF438	IKZF2	Q9UKS7	425
ZNF438	ZSCAN16	Q9H4T2	423
ZNF438	TSGA10IP	Q3SY00	419
ZNF438	ZNF695	Q8IW36	409
ZNF438	ZKSCAN8	Q15776	408
ZNF438	ZNF132	P52740	407
ZNF438	NKAPL	Q5M9Q1	406
ZNF438	ZNF668	Q96K58	403
ZNF438	ZNF165	P49910	397
ZNF438	ZNF10	P21506	392

IntAct

206 interactions, top by confidence:

A	B	Type	Score
SYT17	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	SSX2IP	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	ZNF526	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	PICK1	psi-mi:“MI:0915”(physical association)	0.560
RABEP1	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
FXR1	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	TSGA10	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	BACH2	psi-mi:“MI:0915”(physical association)	0.560
SET	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
KRT40	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
MCC	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
TP53BP2	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	MID2	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	MDFI	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	BANP	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	ZNF629	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	KCTD7	psi-mi:“MI:0915”(physical association)	0.560
YES1	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	SCNM1	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.560
ZNF17	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
ZNF438	PRMT7	psi-mi:“MI:0915”(physical association)	0.560
PLEKHN1	ZNF438	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (76): ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid), ZNF438 (Two-hybrid)

ESM2 similar proteins: A0A0A6YY25, A0A5K7RLP0, A6NMK8, A8MVX0, B2RQL2, B2RXH4, C9JSJ3, D2J0Y4, O54824, P97303, Q01954, Q05AH6, Q0VET5, Q14005, Q1W617, Q2YDE2, Q3MHT3, Q3U0P1, Q3ULM6, Q3UXL4, Q4R7L6, Q5RC05, Q5T0L3, Q68CR7, Q6GQV1, Q6NS69, Q6NZK5, Q6P1D7, Q6PG16, Q6ZVT6, Q7Z4V0, Q80W88, Q80XI1, Q811R2, Q86T90, Q86YN6, Q8BHP2, Q8BLK9, Q8BP99, Q8BW86

Diamond homologs: A0A1V6NWD3, B0ZT45, F9XMW5, J9VX63, O75362, P53243, P56270, P56670, P56671, P78871, Q00453, Q01800, Q02027, Q12132, Q14119, Q4WXK4, Q5RC05, Q7Z4V0, Q9US36, Q9UTS5, S8AKF3, W3X9K7, P60319, Q01611, Q8SW43, Q92618, Q9NUA8, B0X9H6, E9PZZ1, F1QQA8, G5EBU4, O15090, O60315, O62836, O95125, P08048, P17010, P17012, P28166, P31509

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	116
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2121 predictions. Top by Δscore:

Variant	Effect	Δscore
10:30876993:CTTA:C	donor_loss	1.0000
10:30876996:A:AC	donor_gain	1.0000
10:30876997:C:CA	donor_loss	1.0000
10:30876997:C:CC	donor_gain	1.0000
10:30877061:CTTTC:C	acceptor_gain	1.0000
10:30877064:TCC:T	acceptor_loss	1.0000
10:30877066:C:CC	acceptor_gain	1.0000
10:30877067:T:A	acceptor_loss	1.0000
10:30877072:A:AC	acceptor_gain	1.0000
10:30877072:A:C	acceptor_gain	1.0000
10:30884766:TG:T	donor_gain	1.0000
10:30908928:AATAC:A	donor_loss	1.0000
10:30908929:ATACC:A	donor_loss	1.0000
10:30908932:CCT:C	donor_loss	1.0000
10:30908932:CCTT:C	donor_gain	1.0000
10:30909011:CATAC:C	acceptor_gain	1.0000
10:30909013:TAC:T	acceptor_gain	1.0000
10:30909014:ACC:A	acceptor_loss	1.0000
10:30909015:CCTAA:C	acceptor_loss	1.0000
10:30909016:CTA:C	acceptor_loss	1.0000
10:30970906:C:CT	donor_gain	1.0000
10:30970907:T:TT	donor_gain	1.0000
10:30876991:AACTT:A	donor_loss	0.9900
10:30876992:ACTT:A	donor_loss	0.9900
10:30876997:CCTT:C	donor_gain	0.9900
10:30877062:TTTC:T	acceptor_gain	0.9900
10:30877063:TTC:T	acceptor_gain	0.9900
10:30877064:TC:T	acceptor_gain	0.9900
10:30877065:CC:C	acceptor_gain	0.9900
10:30877077:C:CT	acceptor_gain	0.9900

AlphaMissense

5461 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:30848677:A:C	F576L	0.996
10:30848677:A:T	F576L	0.996
10:30848679:A:G	F576L	0.996
10:30848648:A:G	L586P	0.994
10:30848690:C:T	C572Y	0.993
10:30848857:G:C	F516L	0.993
10:30848857:G:T	F516L	0.993
10:30848859:A:G	F516L	0.993
10:30848689:A:C	C572W	0.992
10:30848650:A:C	H585Q	0.991
10:30848650:A:T	H585Q	0.991
10:30848652:G:C	H585D	0.990
10:30848661:A:C	Y582D	0.990
10:30848691:A:G	C572R	0.990
10:30848746:G:C	H553Q	0.990
10:30848746:G:T	H553Q	0.990
10:30848787:A:G	C540R	0.990
10:30848796:A:G	C537R	0.990
10:30848693:A:G	F571S	0.989
10:30848830:G:C	H525Q	0.989
10:30848830:G:T	H525Q	0.989
10:30848630:A:T	V592D	0.988
10:30848700:A:G	C569R	0.988
10:30848858:A:G	F516S	0.988
10:30848699:C:T	C569Y	0.987
10:30848786:C:T	C540Y	0.987
10:30848840:A:G	L522P	0.987
10:30848880:A:G	C509R	0.987
10:30845503:A:G	C649R	0.986
10:30848637:G:C	H590D	0.986

dbSNP variants (sampled 300 via entrez): RS1000016380 (10:30957567 G>A), RS1000027223 (10:30913939 A>C), RS1000029425 (10:30935713 A>T), RS1000058684 (10:31001425 G>A,C), RS1000073792 (10:31018373 C>A,T), RS1000078574 (10:30879426 C>A,T), RS1000112791 (10:30988070 A>G), RS1000121183 (10:30977459 T>C), RS1000153721 (10:31012496 AAT>A), RS1000158216 (10:31030198 C>T), RS1000185622 (10:30970565 G>A), RS1000191509 (10:30892196 T>C,G), RS1000201724 (10:31024848 A>T), RS1000203688 (10:30983617 A>G), RS1000227411 (10:30937471 T>C)

Disease associations

OMIM: gene MIM:620749 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001198_87	Multiple sclerosis	3.000000e-06
GCST002318_167	Rheumatoid arthritis	6.000000e-07
GCST002318_37	Rheumatoid arthritis	1.000000e-09
GCST002574_1	Congenital left-sided heart lesions (maternal effect)	6.000000e-07
GCST002702_22	Height	7.000000e-08
GCST003488_17	Response to fenofibrate (triglyceride levels)	2.000000e-06
GCST006959_111	Rheumatoid arthritis	2.000000e-07
GCST006959_90	Rheumatoid arthritis	8.000000e-06
GCST006979_574	Heel bone mineral density	1.000000e-12
GCST007096_195	Pulse pressure	1.000000e-08
GCST007097_17	Pulse pressure	1.000000e-07
GCST007097_18	Pulse pressure	5.000000e-07
GCST008839_473	Height	4.000000e-15
GCST009597_233	Multiple sclerosis	3.000000e-19
GCST010059_5	Physiological traits	6.000000e-06
GCST010703_265	Brain morphology (MOSTest)	4.000000e-13
GCST90000025_397	Appendicular lean mass	3.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005939	parental genotype effect measurement
EFO:0007681	triglyceride change measurement
EFO:0009270	heel bone mineral density
EFO:0005763	pulse pressure measurement
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass

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
Cadmium Chloride	increases expression, decreases expression	3
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
kojic acid	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	increases expression	1
Doxorubicin	decreases expression	1
Melphalan	decreases expression	1
Methotrexate	increases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation, increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_XW47	HEK293 eGFP-ZNF438	Transformed cell line	Female

Clinical trials (associated diseases)

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