ZNF277

Summary

ZNF277 (zinc finger protein 277, HGNC:13070) is a protein-coding gene on chromosome 7q31.1, encoding Zinc finger protein 277 (Q9NRM2). Probable transcription factor.

Predicted to enable RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and zinc ion binding activity. Predicted to act upstream of or within cellular response to hydrogen peroxide and regulation of cellular senescence. Predicted to be located in nucleus.

Source: NCBI Gene 11179 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 70 total
• Druggable target: yes
• MANE Select transcript: NM_021994

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13070
Approved symbol	ZNF277
Name	zinc finger protein 277
Location	7q31.1
Locus type	gene with protein product
Status	Approved
Aliases	NRIF4
Ensembl gene	ENSG00000198839
Ensembl biotype	protein_coding
OMIM	605465
Entrez	11179

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 nonsense_mediated_decay

ENST00000361822, ENST00000361946, ENST00000421043, ENST00000421864, ENST00000425229, ENST00000450657, ENST00000457808, ENST00000869148, ENST00000869149, ENST00000913151, ENST00000965706

RefSeq mRNA: 1 — MANE Select: NM_021994 NM_021994

CCDS: CCDS5755

Canonical transcript exons

ENST00000361822 — 12 exons

Exon	Start	End
ENSE00001150252	112342561	112343934
ENSE00001150258	112286873	112287074
ENSE00001738609	112206695	112206807
ENSE00003529926	112296229	112296311
ENSE00003602383	112295869	112295957
ENSE00003616268	112330084	112330216
ENSE00003651896	112336104	112336171
ENSE00003656643	112327717	112327827
ENSE00003665615	112339843	112339885
ENSE00003674062	112318182	112318273
ENSE00003688855	112340872	112341046
ENSE00003691618	112337730	112337826

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 93.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.0925 / max 200.9506, expressed in 1797 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80523	19.7717	1796
80522	0.3208	138

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	93.39	gold quality
cortical plate	UBERON:0005343	92.85	gold quality
monocyte	CL:0000576	92.70	gold quality
mononuclear cell	CL:0000842	92.43	gold quality
leukocyte	CL:0000738	92.18	gold quality
germinal epithelium of ovary	UBERON:0001304	90.48	gold quality
islet of Langerhans	UBERON:0000006	90.14	gold quality
body of pancreas	UBERON:0001150	89.26	gold quality
pancreas	UBERON:0001264	88.79	gold quality
tendon	UBERON:0000043	88.64	gold quality
ganglionic eminence	UBERON:0004023	88.55	gold quality
jejunal mucosa	UBERON:0000399	88.25	gold quality
oocyte	CL:0000023	88.20	gold quality
upper leg skin	UBERON:0004262	88.10	gold quality
gall bladder	UBERON:0002110	87.77	gold quality
colonic epithelium	UBERON:0000397	87.24	gold quality
stromal cell of endometrium	CL:0002255	86.94	gold quality
adrenal tissue	UBERON:0018303	86.88	gold quality
rectum	UBERON:0001052	86.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.66	gold quality
granulocyte	CL:0000094	86.65	gold quality
tibial artery	UBERON:0007610	86.51	gold quality
popliteal artery	UBERON:0002250	86.50	gold quality
endometrium	UBERON:0001295	86.16	gold quality
epithelium of nasopharynx	UBERON:0001951	85.78	gold quality
urinary bladder	UBERON:0001255	85.77	gold quality
corpus callosum	UBERON:0002336	85.77	gold quality
upper arm skin	UBERON:0004263	85.73	gold quality
liver	UBERON:0002107	85.71	gold quality
duodenum	UBERON:0002114	85.56	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
BMI1
CDKN2A

miRNA regulators (miRDB)

74 targeting ZNF277, 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-5011-5P	100.00	83.46	5820
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248

Literature-anchored findings (GeneRIF, showing 2)

• ZNF277 microdeletions might contribute to the risk of language impairments (PMID:24518835)
• ZNF277 and PRMT3 compete for uS5 binding, because overexpression of PRMT3 inhibited the formation of the ZNF277-uS5 complex, whereas depletion of cellular ZNF277 resulted in increased levels of uS5-PRMT3. (PMID:30530495)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf277	ENSDARG00000025346
mus_musculus	Zfp277	ENSMUSG00000055917
rattus_norvegicus	Zfp277	ENSRNOG00000045854
drosophila_melanogaster	CG9890	FBGN0034814
caenorhabditis_elegans		WBGENE00009772

Protein

Protein identifiers

Zinc finger protein 277 — Q9NRM2 (reviewed: Q9NRM2)

Alternative names: Nuclear receptor-interacting factor 4

All UniProt accessions (7): Q9NRM2, C9J3B6, C9JH62, E7EW13, F8WBE4, G5E9M4, H7C460

UniProt curated annotations — full annotation on UniProt →

Function. Probable transcription factor. Involved in modulation of cellular senescence; represses transcription of the tumor suppressor gene INK4A/ARF, perhaps acting via the Polycomb group (PcG) complex PRC1.

Subunit / interactions. Interacts (via zinc-finger domains) with RPS2/40S ribosomal protein S2, perhaps as nascent RPS2 is synthesized during translation; the interaction is direct; the interaction is extra-ribosomal. Interaction with RPS2 competes with the binding of RPS2 to protein arginine methyltransferase PRMT3. Interacts with Polycomb group (PcG) complex protein BMI1. May be part of a complex including at least ZNF277, BMI1 and RNF2/RING2.

Subcellular location. Nucleus.

Induction. Down-regulated by oxidative stress.

Similarity. Belongs to the ZNF277 family.

RefSeq proteins (1): NP_068834* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR040048	ZNF277	Family
IPR041661	ZN622/Rei1/Reh1_Znf-C2H2	Domain

Pfam: PF12756

UniProt features (13 total): mutagenesis site 4, sequence variant 4, zinc finger region 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRM2-F1	75.02	0.13

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): 2

Mutagenesis-validated functional residues (4):

Position	Phenotype
226–248	modest reduction in binding to rps2.
304–325	drastic reduction in binding to rps2.
359–381	modest reduction in binding to rps2.
175–197	modest reduction in binding to rps2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 149 (showing top): MYAATNNNNNNNGGC_UNKNOWN, NKX25_02, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, CAGCTG_AP4_Q5, AACWWCAANK_UNKNOWN, SOX9_B1, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, TGANTCA_AP1_C, AACTTT_UNKNOWN, ACEVEDO_LIVER_CANCER_UP, RODRIGUES_DCC_TARGETS_DN, YNGTTNNNATT_UNKNOWN

GO Biological Process (2): cellular response to hydrogen peroxide (GO:0070301), regulation of cellular senescence (GO:2000772)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), 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)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
regulation of cellular process	1
cellular senescence	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	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

764 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF277	DOCK4	Q8N1I0	582
ZNF277	IKZF1	Q13422	548
ZNF277	RPS2	P15880	527
ZNF277	TMEM186	Q96B77	517
ZNF277	PDCD2L	Q9BRP1	503
ZNF277	SF3A2	Q15428	458
ZNF277	TMEM258	P61165	458
ZNF277	ZMAT5	Q9UDW3	449
ZNF277	PDCD2	Q16342	443
ZNF277	MOV10	Q9HCE1	440
ZNF277	ZMAT2	Q96NC0	432
ZNF277	RNF167	Q9H6Y7	418
ZNF277	PRMT3	O60678	410
ZNF277	PDE3B	Q13370	398
ZNF277	RELA	Q04206	396

IntAct

32 interactions, top by confidence:

A	B	Type	Score
MAP2K1	RAF1	psi-mi:“MI:0914”(association)	0.960
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF277	RNF123	psi-mi:“MI:0914”(association)	0.530
ZNF277	GNGT1	psi-mi:“MI:0915”(physical association)	0.370
DDB1	ZNF277	psi-mi:“MI:0915”(physical association)	0.370
ZNF277	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.370
ZNF277	ZNF768	psi-mi:“MI:0915”(physical association)	0.370
ZNF277	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
Gpkow	BDP1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
STX19	SULT1A2	psi-mi:“MI:0914”(association)	0.350
STX19	SNAP23	psi-mi:“MI:0914”(association)	0.350
PDCD2	PRMT3	psi-mi:“MI:0914”(association)	0.350
GPRC5C	ZNF277	psi-mi:“MI:0915”(physical association)	0.000
ZNF277	ACOT2	psi-mi:“MI:0915”(physical association)	0.000
ZNF277	ilvD	psi-mi:“MI:0915”(physical association)	0.000
ZNF277		psi-mi:“MI:0915”(physical association)	0.000
ZNF277	nrdF	psi-mi:“MI:0915”(physical association)	0.000
ZNF277	ileS2	psi-mi:“MI:0915”(physical association)	0.000
rpoB	ZNF277	psi-mi:“MI:0915”(physical association)	0.000
	ZNF277	psi-mi:“MI:0915”(physical association)	0.000
glnH	ZNF277	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (60): ZNF277 (Two-hybrid), ZNF277 (Two-hybrid), MBD3 (Two-hybrid), NUTM1 (Two-hybrid), ZNF277 (Affinity Capture-MS), ZNF277 (Affinity Capture-MS), UBE2T (Affinity Capture-MS), RNF123 (Affinity Capture-MS), ZNF277 (Affinity Capture-MS), ZNF277 (Affinity Capture-MS), ZNF277 (Affinity Capture-MS), ZNF277 (Affinity Capture-MS), ZNF277 (Affinity Capture-MS), UBE2T (Affinity Capture-MS), RNF123 (Affinity Capture-MS)

ESM2 similar proteins: A1L3L1, A3KPW7, B0K012, D3ZV31, E1BGQ2, F1ND48, O55055, P50747, P61798, Q08DP1, Q0IHB3, Q149N8, Q15650, Q1RMU2, Q1RMZ1, Q3U269, Q3U2J5, Q5RCP1, Q5RCQ0, Q5RED8, Q5T7W7, Q5ZIA0, Q5ZJ87, Q66H62, Q66IH9, Q6AYF5, Q6DCD7, Q6GQ33, Q6GR37, Q6NYU2, Q6PF06, Q7SY78, Q7TPQ3, Q7YRZ2, Q7Z2E3, Q80TQ2, Q8BKW4, Q8BXK4, Q8IWR0, Q8K2I9

Diamond homologs: A2XYY8, A2Y8B9, A2YP56, A2YPT7, A2Z0C0, A2Z8S0, A3BMN9, A3DF23, A3KPF2, A5G9G5, A5IN97, A6LJG3, A8IEF3, B0JYW5, B0X4N1, B1L841, B3DLB3, B3M1E1, B3P4N5, B4GZ20, B4HJC0, B4JXV2, B4KA23, B4LVS8, B4NKI9, B4PVH6, B4QVW6, B9K9N3, D9IVE5, E9Q6D6, O13648, O60678, O70467, O82210, O86951, P38074, P55345, Q08A71, Q0J2C6, Q0WVD6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1823 predictions. Top by Δscore:

Variant	Effect	Δscore
7:112206759:G:GT	donor_gain	1.0000
7:112286860:T:TA	acceptor_gain	1.0000
7:112286866:A:AG	acceptor_gain	1.0000
7:112286871:A:AG	acceptor_gain	1.0000
7:112286872:G:GA	acceptor_gain	1.0000
7:112286872:GACA:G	acceptor_gain	1.0000
7:112287070:CAAAG:C	donor_gain	1.0000
7:112287072:AAG:A	donor_gain	1.0000
7:112287072:AAGG:A	donor_loss	1.0000
7:112287073:AG:A	donor_gain	1.0000
7:112287073:AGG:A	donor_loss	1.0000
7:112287074:GG:G	donor_gain	1.0000
7:112287074:GGTA:G	donor_loss	1.0000
7:112287075:G:GA	donor_loss	1.0000
7:112287075:G:GG	donor_gain	1.0000
7:112287076:T:A	donor_loss	1.0000
7:112296216:A:AG	acceptor_gain	1.0000
7:112296217:A:AG	acceptor_gain	1.0000
7:112296218:T:G	acceptor_gain	1.0000
7:112296227:A:AG	acceptor_gain	1.0000
7:112296228:G:GC	acceptor_gain	1.0000
7:112296228:GAA:G	acceptor_gain	1.0000
7:112296307:GACTG:G	donor_gain	1.0000
7:112296308:ACTGG:A	donor_loss	1.0000
7:112296309:CTGG:C	donor_loss	1.0000
7:112296310:TGGTA:T	donor_loss	1.0000
7:112296311:GGTAA:G	donor_loss	1.0000
7:112296312:G:GG	donor_gain	1.0000
7:112296312:GTA:G	donor_loss	1.0000
7:112296313:T:A	donor_loss	1.0000

AlphaMissense

3031 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:112330091:T:C	C226R	0.998
7:112330131:T:C	L239P	0.998
7:112318239:T:C	C175R	0.997
7:112330147:G:C	R244S	0.997
7:112330147:G:T	R244S	0.997
7:112318213:G:C	R166P	0.996
7:112330091:T:A	C226S	0.996
7:112330092:G:C	C226S	0.996
7:112330139:C:G	H242D	0.996
7:112330141:C:A	H242Q	0.996
7:112330141:C:G	H242Q	0.996
7:112340914:G:C	R351P	0.996
7:112330093:C:G	C226W	0.995
7:112330131:T:A	L239H	0.995
7:112330146:G:C	R244T	0.995
7:112296287:A:C	R147S	0.994
7:112296287:A:T	R147S	0.994
7:112318241:T:G	C175W	0.994
7:112327764:G:A	G202E	0.994
7:112330112:T:C	F233L	0.994
7:112330114:C:A	F233L	0.994
7:112330114:C:G	F233L	0.994
7:112330157:C:G	H248D	0.993
7:112330159:T:A	H248Q	0.993
7:112330159:T:G	H248Q	0.993
7:112337770:T:C	C304R	0.993
7:112340906:T:A	N348K	0.993
7:112340906:T:G	N348K	0.993
7:112327750:T:A	H197Q	0.992
7:112327750:T:G	H197Q	0.992

dbSNP variants (sampled 300 via entrez): RS1000009722 (7:112306781 T>A), RS1000059072 (7:112212796 T>C,G), RS1000085830 (7:112205558 G>C), RS1000099784 (7:112257587 T>G), RS1000103393 (7:112237491 T>A), RS1000114528 (7:112237215 C>T), RS1000151453 (7:112303369 G>A), RS1000160508 (7:112288448 T>C,G), RS1000191231 (7:112213481 A>G), RS1000191313 (7:112269253 T>G), RS1000196004 (7:112304910 A>C), RS1000226687 (7:112277982 A>G), RS1000228793 (7:112264452 A>G), RS1000235958 (7:112231952 G>GT), RS1000260876 (7:112330689 C>G)

Disease associations

OMIM: gene MIM:605465 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001585_25	Breast size	6.000000e-06
GCST004138_8	Early-onset Parkinson’s disease	2.000000e-16
GCST010002_260	Refractive error	3.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067158 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Kd	1.008	nM	CHEMBL5653589
8.72	ED50	1.909	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149816: Binding affinity to human ZNF277 incubated for 45 mins by Kinobead based pull down assay	kd	0.0010	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Valproic Acid	increases expression, affects expression	3
trichostatin A	affects expression, increases expression	2
cobaltous chloride	increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	decreases methylation	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
cupric oxide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
pentabromodiphenyl ether	increases expression	1
K 7174	increases expression	1
torcetrapib	increases expression	1
ICG 001	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
MT19c compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652858	Binding	Binding affinity to human ZNF277 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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