ZNF74

Summary

ZNF74 (zinc finger protein 74, HGNC:13144) is a protein-coding gene on chromosome 22q11.21, encoding Zinc finger protein 74 (Q16587). May play a role in RNA metabolism.

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 transcription by RNA polymerase II. Located in actin cytoskeleton and nucleoplasm.

Source: NCBI Gene 7625 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 97 total
• MANE Select transcript: NM_003426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13144
Approved symbol	ZNF74
Name	zinc finger protein 74
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	Cos52, Zfp520, ZNF520
Ensembl gene	ENSG00000185252
Ensembl biotype	protein_coding
OMIM	194548
Entrez	7625

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000357502, ENST00000400451, ENST00000403682, ENST00000405993, ENST00000420626, ENST00000437275, ENST00000476678, ENST00000493734, ENST00000611540, ENST00000908224, ENST00000923876

RefSeq mRNA: 4 — MANE Select: NM_003426 NM_001256523, NM_001256524, NM_001256525, NM_003426

CCDS: CCDS42982, CCDS58794

Canonical transcript exons

ENST00000400451 — 5 exons

Exon	Start	End
ENSE00001879391	20394151	20394662
ENSE00001900871	20405377	20408455
ENSE00003514535	20401277	20401372
ENSE00003587165	20395333	20395418
ENSE00003744736	20400632	20400758

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 91.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.5892 / max 104.2428, expressed in 1613 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191123	3.6945	1385
191124	2.8947	1269

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	91.27	gold quality
ganglionic eminence	UBERON:0004023	88.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.22	gold quality
ventricular zone	UBERON:0003053	83.69	gold quality
adrenal tissue	UBERON:0018303	79.96	gold quality
embryo	UBERON:0000922	79.16	gold quality
buccal mucosa cell	CL:0002336	78.96	silver quality
cerebellar vermis	UBERON:0004720	78.82	gold quality
tendon of biceps brachii	UBERON:0008188	78.67	silver quality
stromal cell of endometrium	CL:0002255	78.37	gold quality
granulocyte	CL:0000094	78.16	gold quality
prefrontal cortex	UBERON:0000451	77.51	gold quality
endothelial cell	CL:0000115	77.34	gold quality
parotid gland	UBERON:0001831	76.98	gold quality
right frontal lobe	UBERON:0002810	76.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.56	gold quality
cerebellar hemisphere	UBERON:0002245	76.54	gold quality
cerebellar cortex	UBERON:0002129	76.53	gold quality
cerebellum	UBERON:0002037	75.90	gold quality
anterior cingulate cortex	UBERON:0009835	75.75	gold quality
cingulate cortex	UBERON:0003027	75.72	gold quality
adenohypophysis	UBERON:0002196	75.67	gold quality
mammary duct	UBERON:0001765	75.62	silver quality
neocortex	UBERON:0001950	75.51	gold quality
lower esophagus mucosa	UBERON:0035834	75.22	gold quality
frontal cortex	UBERON:0001870	75.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.15	gold quality
pituitary gland	UBERON:0000007	74.79	gold quality
lateral globus pallidus	UBERON:0002476	74.58	gold quality
vena cava	UBERON:0004087	74.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

69 targeting ZNF74, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-142-5P	99.48	70.92	2416

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 74 — Q16587 (reviewed: Q16587)

Alternative names: Zinc finger protein 520, hZNF7

All UniProt accessions (4): Q16587, B5MDQ6, C9J3V1, F8WDT0

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in RNA metabolism.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in the fetal brain.

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q16587-1	2	yes
Q16587-2	1
Q16587-3	3
Q16587-4	4
Q16587-5	5

RefSeq proteins (4): NP_001243452, NP_001243453, NP_001243454, NP_003417* (*=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 12, splice variant 5, sequence conflict 3, sequence variant 2, chain 1, domain 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16587-F1	65.94	0.08

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 582

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 90 (showing top): MODULE_397, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, NOTCH_DN.V1_DN, RPS14_DN.V1_DN, TGFB_UP.V1_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ARID5B_TARGET_GENES, BCL6B_TARGET_GENES, HMG20B_TARGET_GENES, HOXC6_TARGET_GENES, NKX2_2_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), RNA binding (GO:0003723), zinc ion binding (GO:0008270), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), actin cytoskeleton (GO:0015629), cytoskeleton (GO:0005856), nuclear lumen (GO:0031981)

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
nucleic acid 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
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
cytoskeleton	1
intracellular membraneless organelle	1
nucleus	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

492 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF74	MED15	Q96RN5	846
ZNF74	DGCR6	Q14129	842
ZNF74	DGCR6L	Q9BY27	841
ZNF74	C9JR48	C9JR48	822
ZNF74	DGCR2	P98153	809
ZNF74	HIRA	P54198	775
ZNF74	TBX1	O43435	661
ZNF74	ZDHHC8	Q9ULC8	610
ZNF74	SCARF2	Q96GP6	583
ZNF74	THAP7	Q9BT49	575
ZNF74	GNB1L	Q9BYB4	572
ZNF74	GSC2	O15499	560
ZNF74	COMT	P21964	558
ZNF74	LZTR1	Q8N653	542
ZNF74	PI4KA	P42356	509

IntAct

16 interactions, top by confidence:

A	B	Type	Score
TRIM28	ZNF316	psi-mi:“MI:0914”(association)	0.530
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF74	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
PB2	ZNF74	psi-mi:“MI:0915”(physical association)	0.370
ZNF304	IPO8	psi-mi:“MI:0914”(association)	0.350
ZNF74	ZNF316	psi-mi:“MI:0914”(association)	0.350
FBLN5	ZNF320	psi-mi:“MI:0914”(association)	0.350
ZNF460	ZNF320	psi-mi:“MI:0914”(association)	0.350
LTBP2	ZNF320	psi-mi:“MI:0914”(association)	0.350
ZNF74	GAPDHS	psi-mi:“MI:0914”(association)	0.350
IKZF4	OBSL1	psi-mi:“MI:0914”(association)	0.350
TNNC2	ECI2	psi-mi:“MI:0914”(association)	0.350
ZNF74	DVL1	psi-mi:“MI:0914”(association)	0.350
ZNF74	DCTN6	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): ZNF74 (Affinity Capture-MS), ZNF74 (Affinity Capture-MS), TRIM28 (FRET), POLR2A (Affinity Capture-Western), POLR2A (Far Western), FBXO11 (Affinity Capture-MS), LZTS2 (Affinity Capture-MS), ZNF74 (Affinity Capture-MS), SNX18 (Affinity Capture-MS), SORL1 (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), ZNF74 (Affinity Capture-MS), TRIM41 (Affinity Capture-MS), RBAK (Affinity Capture-MS), ZNF74 (Affinity Capture-MS)

ESM2 similar proteins: A3KN32, A6NM28, A8K8V0, E9PYI1, O75467, O95201, P10072, P10075, P10078, P10754, P28698, P30373, P52736, Q0VCC5, Q14929, Q16587, Q17QR7, Q29RZ4, Q3KNW1, Q3TDE8, Q3US17, Q58DK7, Q5RJR4, Q5T619, Q5TEC3, Q5U4E2, Q62396, Q68H95, Q6AW86, Q6PGE4, Q6ZMY9, Q7Z398, Q7Z7K2, Q8BI73, Q8BIF9, Q8BIQ3, Q8BKK5, Q8JZL0, Q8N393, Q8R0T2

Diamond homologs: A0A1W2PQL4, A0JNB1, A0JPL0, A6NK53, A6QLU5, A6QPT6, A7MBI1, A8MT65, A8MUV8, A8MWA4, B2RXC5, B4DU55, B4DX44, E9PYI1, O14628, O75346, P0CH99, P0CI00, P17014, P17030, P17032, P17098, P51786, P85977, Q02386, Q06730, Q06732, Q0VAW7, Q12901, Q13360, Q14586, Q14588, Q14590, Q16587, Q2M3X9, Q2VY69, Q32M78, Q3ZCX4, Q49AA0, Q4R6J4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

917 predictions. Top by Δscore:

Variant	Effect	Δscore
22:20394662:GG:G	donor_loss	0.9900
22:20405375:A:AG	acceptor_gain	0.9900
22:20405376:G:GG	acceptor_gain	0.9900
22:20401270:C:CA	acceptor_gain	0.9800
22:20394658:GACAG:G	donor_gain	0.9700
22:20395327:CGCCA:C	acceptor_gain	0.9700
22:20395328:GCCAG:G	acceptor_gain	0.9700
22:20395329:CCAG:C	acceptor_gain	0.9700
22:20395330:CAGC:C	acceptor_gain	0.9700
22:20405375:AGAAT:A	acceptor_gain	0.9700
22:20405376:GA:G	acceptor_gain	0.9700
22:20405376:GAAT:G	acceptor_gain	0.9700
22:20405376:GAATG:G	acceptor_gain	0.9700
22:20401368:TCCAG:T	donor_loss	0.9600
22:20401369:CCAGG:C	donor_loss	0.9600
22:20401370:CAG:C	donor_loss	0.9600
22:20401371:AGG:A	donor_loss	0.9600
22:20401372:GGT:G	donor_loss	0.9600
22:20401373:GTGA:G	donor_loss	0.9600
22:20401374:T:TC	donor_loss	0.9600
22:20394369:GGGGC:G	donor_gain	0.9500
22:20394370:GGGCG:G	donor_gain	0.9500
22:20394681:AGTC:A	donor_gain	0.9500
22:20395331:AGC:A	acceptor_gain	0.9500
22:20395332:G:T	acceptor_gain	0.9500
22:20395414:CCAAG:C	donor_loss	0.9500
22:20395415:CAAGG:C	donor_loss	0.9500
22:20395416:AAG:A	donor_loss	0.9500
22:20395419:G:GA	donor_loss	0.9500
22:20395420:T:G	donor_loss	0.9500

AlphaMissense

4276 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:20405886:T:C	F285L	1.000
22:20405888:C:A	F285L	1.000
22:20405888:C:G	F285L	1.000
22:20405970:T:C	F313L	1.000
22:20405972:C:A	F313L	1.000
22:20405972:C:G	F313L	1.000
22:20406004:G:C	R324P	0.999
22:20406054:T:C	F341L	0.999
22:20406056:C:A	F341L	0.999
22:20406056:C:G	F341L	0.999
22:20406138:T:C	F369L	0.999
22:20406140:C:A	F369L	0.999
22:20406140:C:G	F369L	0.999
22:20406222:T:C	F397L	0.999
22:20406224:C:A	F397L	0.999
22:20406224:C:G	F397L	0.999
22:20406306:T:C	F425L	0.999
22:20406308:C:A	F425L	0.999
22:20406308:C:G	F425L	0.999
22:20406390:T:C	F453L	0.999
22:20406392:C:A	F453L	0.999
22:20406392:C:G	F453L	0.999
22:20406474:T:C	F481L	0.999
22:20406476:C:A	F481L	0.999
22:20406476:C:G	F481L	0.999
22:20406558:T:C	F509L	0.999
22:20406560:C:A	F509L	0.999
22:20406560:C:G	F509L	0.999
22:20406642:T:C	F537L	0.999
22:20406644:C:A	F537L	0.999

dbSNP variants (sampled 300 via entrez): RS1000031548 (22:20403447 G>A), RS1000253445 (22:20397059 T>G), RS1000955966 (22:20398764 A>G), RS1001310263 (22:20394195 T>C), RS1001381342 (22:20392907 C>T), RS1001896663 (22:20400090 G>A), RS1001931654 (22:20394214 C>G), RS1002211781 (22:20406132 A>G), RS1002276058 (22:20394087 C>T), RS1002836508 (22:20395755 C>T), RS1002955650 (22:20404861 A>G), RS1002993714 (22:20395618 G>A), RS1003130634 (22:20401517 T>C,G), RS1003170454 (22:20397051 G>A), RS1003276568 (22:20396506 A>G)

Disease associations

OMIM: gene MIM:194548 | 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

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, decreases expression	8
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
titanium dioxide	increases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Zoledronic Acid	increases expression	1
Vorinostat	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Catechin	increases expression, affects cotreatment	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
N-Nitrosopyrrolidine	increases expression	1
Ozone	increases abundance, affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	decreases expression	1
Volatile Organic Compounds	decreases expression, affects cotreatment	1

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8K3	SEES3-1V human ZNF74, clone1	Embryonic stem cell	Male
CVCL_A8K4	SEES3-1V human ZNF74, clone2	Embryonic stem cell	Male
CVCL_A8K5	SEES3-1V human ZNF74, clone3	Embryonic stem cell	Male
CVCL_TZ43	HAP1 ZNF74 (-) 1	Cancer cell line	Male
CVCL_TZ44	HAP1 ZNF74 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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