ZNF774

Summary

ZNF774 (zinc finger protein 774, HGNC:33108) is a protein-coding gene on chromosome 15q26.1, encoding Zinc finger protein 774 (Q6NX45). May be involved in transcriptional regulation.

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. Predicted to be active in nucleus.

Source: NCBI Gene 342132 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 88 total
• MANE Select transcript: NM_001004309

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33108
Approved symbol	ZNF774
Name	zinc finger protein 774
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC75360
Ensembl gene	ENSG00000196391
Ensembl biotype	protein_coding
Entrez	342132

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000354377, ENST00000379090, ENST00000558115, ENST00000558586, ENST00000560038

RefSeq mRNA: 1 — MANE Select: NM_001004309 NM_001004309

CCDS: CCDS32330

Canonical transcript exons

ENST00000354377 — 4 exons

Exon	Start	End
ENSE00001403787	90354642	90354764
ENSE00001407550	90352284	90352411
ENSE00001426164	90360043	90362847
ENSE00003499758	90358851	90358957

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 79.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1.8565 / max 32.3054, expressed in 1042 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148441	1.8565	1042

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue	UBERON:0001134	79.07	gold quality
gastrocnemius	UBERON:0001388	78.68	gold quality
adrenal tissue	UBERON:0018303	78.65	gold quality
rectum	UBERON:0001052	78.61	gold quality
corpus callosum	UBERON:0002336	78.08	gold quality
muscle of leg	UBERON:0001383	78.04	gold quality
right coronary artery	UBERON:0001625	76.95	gold quality
muscle tissue	UBERON:0002385	75.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.74	gold quality
tibial artery	UBERON:0007610	75.52	gold quality
popliteal artery	UBERON:0002250	75.51	gold quality
cortical plate	UBERON:0005343	75.29	gold quality
colonic epithelium	UBERON:0000397	75.05	gold quality
prefrontal cortex	UBERON:0000451	73.99	gold quality
cerebellum	UBERON:0002037	73.99	gold quality
cerebellar cortex	UBERON:0002129	73.99	gold quality
ganglionic eminence	UBERON:0004023	73.97	gold quality
cerebellar hemisphere	UBERON:0002245	73.91	gold quality
right uterine tube	UBERON:0001302	73.73	gold quality
right adrenal gland cortex	UBERON:0035827	73.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	73.63	gold quality
superior frontal gyrus	UBERON:0002661	73.56	gold quality
left coronary artery	UBERON:0001626	73.17	gold quality
islet of Langerhans	UBERON:0000006	73.13	gold quality
ventricular zone	UBERON:0003053	72.98	gold quality
pancreas	UBERON:0001264	72.93	gold quality
right adrenal gland	UBERON:0001233	72.91	gold quality
mucosa of transverse colon	UBERON:0004991	72.90	gold quality
adrenal gland	UBERON:0002369	72.53	gold quality
body of pancreas	UBERON:0001150	72.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.10
E-MTAB-6386	no	43.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting ZNF774, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-3908	98.75	67.31	1160
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-376C-3P	97.63	68.88	1263
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-4535	97.27	65.17	469
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-6786-3P	93.73	60.70	52

Literature-anchored findings (GeneRIF, showing 1)

• ZNF774 is a potent suppressor of hepatocarcinogenesis through dampening the NOTCH2 signaling. (PMID:31659254)

Cross-species orthologs

0 orthologs

Paralogs (51): WIZ (ENSG00000011451), ZNF416 (ENSG00000083817), MYNN (ENSG00000085274), PRDM4 (ENSG00000110851), PRDM2 (ENSG00000116731), ZBTB17 (ENSG00000116809), ZNF644 (ENSG00000122482), GZF1 (ENSG00000125812), ZNF426 (ENSG00000130818), ZNF287 (ENSG00000141040), ZNF697 (ENSG00000143067), ZNF687 (ENSG00000143373), ZNF214 (ENSG00000149050), ZNF547 (ENSG00000152433), ZNF776 (ENSG00000152443), ZNF230 (ENSG00000159882), ZNF222 (ENSG00000159885), ZNF233 (ENSG00000159915), ZNF333 (ENSG00000160961), ZNF319 (ENSG00000166188), ZNF592 (ENSG00000166716), ZNF646 (ENSG00000167395), ZNF507 (ENSG00000168813), ZNF768 (ENSG00000169957), ZNF417 (ENSG00000173480), ZNF408 (ENSG00000175213), ZBTB41 (ENSG00000177888), ZNF223 (ENSG00000178386), ZNF852 (ENSG00000178917), ZNF784 (ENSG00000179922), ZNF572 (ENSG00000180938), ZNF707 (ENSG00000181135), ZNF746 (ENSG00000181220), ZNF467 (ENSG00000181444), ZNF530 (ENSG00000183647), ZNF17 (ENSG00000186272), ZNF527 (ENSG00000189164), ZKSCAN7 (ENSG00000196345), ZNF34 (ENSG00000196378), ZNF777 (ENSG00000196453)

Protein

Protein identifiers

Zinc finger protein 774 — Q6NX45 (reviewed: Q6NX45)

All UniProt accessions (4): E7EQ77, Q6NX45, H0YLG8, H0YNW6

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 (1): NP_001004309* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (19 total): zinc finger region 12, sequence variant 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-Q6NX45-F1	73.02	0.56

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 37 (showing top): GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, chr15q26, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ASH1L_TARGET_GENES, CEBPZ_TARGET_GENES, E2F2_TARGET_GENES, ELF2_TARGET_GENES, HES4_TARGET_GENES, NKX2_2_TARGET_GENES, PRKDC_TARGET_GENES, RBM34_TARGET_GENES, ZFHX3_TARGET_GENES, ZNF711_TARGET_GENES, MIR6760_5P

GO Biological Process (1): 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 (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	2
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

Protein interactions and networks

STRING

546 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF774	ZNF385B	Q569K4	573
ZNF774	ZNF827	Q17R98	560
ZNF774	TSHZ3	Q63HK5	500
ZNF774	SIRAL2	Q9NWS6	419
ZNF774	PRR14	Q9BWN1	416
ZNF774	FBRS	Q9HAH7	391
ZNF774	TTK	P33981	366
ZNF774	BCL7C	Q8WUZ0	349
ZNF774	CCDC88B	A6NC98	344
ZNF774	ZNF559	Q9BR84	342
ZNF774	SPATA24	Q86W54	330
ZNF774	ZBTB21	Q9ULJ3	329
ZNF774	ZNF462	Q96JM2	324
ZNF774	FEM1B	Q9UK73	314
ZNF774	PHF8	Q9UPP1	299

IntAct

278 interactions, top by confidence:

A	B	Type	Score
ZNF774	GOLGA2	psi-mi:“MI:0915”(physical association)	0.780
GOLGA2	ZNF774	psi-mi:“MI:0915”(physical association)	0.780
BEGAIN	ZNF774	psi-mi:“MI:0915”(physical association)	0.720
ZNF774	BEGAIN	psi-mi:“MI:0915”(physical association)	0.720
GFAP	ZNF774	psi-mi:“MI:0915”(physical association)	0.720
LDOC1	ZNF774	psi-mi:“MI:0915”(physical association)	0.670
ZNF774	LDOC1	psi-mi:“MI:0915”(physical association)	0.670
ZNF774	RBM11	psi-mi:“MI:0915”(physical association)	0.560
BYSL	ZNF774	psi-mi:“MI:0915”(physical association)	0.560
FANCL	ZNF774	psi-mi:“MI:0915”(physical association)	0.560
CPNE7	ZNF774	psi-mi:“MI:0915”(physical association)	0.560
PIBF1	ZNF774	psi-mi:“MI:0915”(physical association)	0.560
CARD9	ZNF774	psi-mi:“MI:0915”(physical association)	0.560
ENKD1	ZNF774	psi-mi:“MI:0915”(physical association)	0.560
MISP	ZNF774	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (82): ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid), ZNF774 (Two-hybrid)

ESM2 similar proteins: A0JNB1, A1YF12, A1YG88, A2T759, A3KN32, B2RUI1, O43296, O75123, P10072, P17020, P17097, P51814, P52736, P52740, Q07230, Q08ER8, Q13398, Q14590, Q32KN0, Q3KQV3, Q3MIS6, Q4V8A8, Q5CZA5, Q5RBQ3, Q5RBX0, Q5RCD9, Q5RCX4, Q6GQR8, Q6NX45, Q6P9A3, Q6PK81, Q7TSH9, Q7TSI0, Q7Z7L9, Q86UD4, Q8BFS8, Q8BLB0, Q8IVP9, Q8IZ26, Q8N9F8

Diamond homologs: P08045, P18715, P18720, P18726, P18731, P18736, P18737, P18738, P18741, P18743, P18753, P18853, P51815, Q3MJ62, Q3TDE8, Q3US17, Q62513, Q62981, Q6A085, Q6NX45, Q6P1L6, Q7TNU6, Q8BLB0, Q92670, Q96NJ6, Q9UEG4, A2ANX9, B0YDH7, O15391, O57311, O57415, O60315, O60481, O62836, O73689, O95409, P03001, P08048, P0C6P6, P10925

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ZNF774	“up-regulates activity”	“MBD2/NuRD complex”	binding
ZNF774	“up-regulates activity”	“MBD3/NuRD complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

757 predictions. Top by Δscore:

Variant	Effect	Δscore
15:90352407:GGGCG:G	donor_gain	0.9900
15:90352408:GGCG:G	donor_gain	0.9900
15:90352408:GGCGG:G	donor_gain	0.9900
15:90352409:GCG:G	donor_gain	0.9900
15:90352409:GCGG:G	donor_gain	0.9900
15:90352410:CGGTG:C	donor_loss	0.9900
15:90352411:GGTG:G	donor_loss	0.9900
15:90352412:GTGA:G	donor_loss	0.9900
15:90352413:T:A	donor_loss	0.9900
15:90352414:G:GG	donor_loss	0.9900
15:90358848:TAGAA:T	acceptor_gain	0.9900
15:90358849:A:AG	acceptor_gain	0.9900
15:90358850:G:GG	acceptor_gain	0.9900
15:90352412:G:GG	donor_gain	0.9800
15:90352426:G:GT	donor_gain	0.9800
15:90352462:G:T	donor_gain	0.9800
15:90358846:TGTAG:T	acceptor_gain	0.9800
15:90358847:GTAGA:G	acceptor_gain	0.9800
15:90358849:AGAA:A	acceptor_gain	0.9800
15:90358850:GAAT:G	acceptor_gain	0.9800
15:90352415:A:AC	donor_loss	0.9700
15:90355414:G:GT	donor_gain	0.9700
15:90358850:GA:G	acceptor_gain	0.9700
15:90358850:GAA:G	acceptor_gain	0.9700
15:90360041:A:AG	acceptor_gain	0.9700
15:90360042:G:GG	acceptor_gain	0.9700
15:90360042:GACT:G	acceptor_gain	0.9700
15:90360030:A:AG	acceptor_gain	0.9600
15:90360031:T:G	acceptor_gain	0.9600
15:90352416:G:C	donor_loss	0.9500

AlphaMissense

3232 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:90360393:T:C	F188L	0.999
15:90360395:C:A	F188L	0.999
15:90360395:C:G	F188L	0.999
15:90360477:T:C	F216L	0.999
15:90360479:C:A	F216L	0.999
15:90360479:C:G	F216L	0.999
15:90360645:T:C	F272L	0.999
15:90360647:C:A	F272L	0.999
15:90360647:C:G	F272L	0.999
15:90360729:T:C	F300L	0.999
15:90360731:T:A	F300L	0.999
15:90360731:T:G	F300L	0.999
15:90360897:T:C	F356L	0.999
15:90360899:C:A	F356L	0.999
15:90360899:C:G	F356L	0.999
15:90360981:T:C	F384L	0.999
15:90360983:C:A	F384L	0.999
15:90360983:C:G	F384L	0.999
15:90361015:G:C	R395P	0.999
15:90361065:T:C	F412L	0.999
15:90361067:C:A	F412L	0.999
15:90361067:C:G	F412L	0.999
15:90360412:T:C	L194P	0.998
15:90360561:T:C	F244L	0.998
15:90360563:T:A	F244L	0.998
15:90360563:T:G	F244L	0.998
15:90360580:T:C	L250P	0.998
15:90360763:G:C	R311P	0.998
15:90360813:T:C	F328L	0.998
15:90360815:C:A	F328L	0.998

dbSNP variants (sampled 300 via entrez): RS1000347888 (15:90363793 G>A,T), RS1000487147 (15:90354013 T>G), RS1000509981 (15:90354267 C>A), RS1000818431 (15:90366411 C>T), RS1001078058 (15:90365093 G>C), RS1001466338 (15:90352453 C>G), RS1001629034 (15:90359307 C>T), RS1001721413 (15:90364360 A>G), RS1001797960 (15:90365458 G>A), RS1001818693 (15:90365158 C>T), RS1001996406 (15:90359141 C>T), RS1002196611 (15:90353328 T>C), RS1002306455 (15:90359589 G>T), RS1002602427 (15:90357955 G>A,C), RS1002626816 (15:90358147 A>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:210900, MIM:613657

GenCC curated gene-disease

Mondo (2): Bloom syndrome (MONDO:0008876), d-2-hydroxyglutaric aciduria 2 (MONDO:0013345)

Orphanet (2): Bloom syndrome (Orphanet:125), D-2-hydroxyglutaric aciduria (Orphanet:79315)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001454_13	Rheumatoid arthritis	1.000000e-06
GCST006661_175	Male-pattern baldness	2.000000e-11

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001816	Bloom Syndrome	C16.131.077.137; C16.320.798.313; C18.452.284.100; C20.673.795.313

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
jinfukang	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Magnetite Nanoparticles	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00021437	Not specified	COMPLETED	Biological Significance of the Bloom’s Syndrome Protein
NCT04251325	Not specified	UNKNOWN	Socio-demographic Characteristics of Basic Life Support Course Participants
NCT04353089	Not specified	UNKNOWN	Geographical Association Between Basic Life Support Courses, Bystander Cardiopulmonary Resuscitation and Survival