ZNF280D

Summary

ZNF280D (zinc finger protein 280D, HGNC:25953) is a protein-coding gene on chromosome 15q21.3, encoding Zinc finger protein 280D (Q6N043). May function as a transcription factor.

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 nucleus.

Source: NCBI Gene 54816 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 136 total
• Druggable target: yes
• MANE Select transcript: NM_017661

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25953
Approved symbol	ZNF280D
Name	zinc finger protein 280D
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20086, ZNF634
Ensembl gene	ENSG00000137871
Ensembl biotype	protein_coding
Entrez	54816

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 8 protein_coding, 5 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000267807, ENST00000558002, ENST00000558067, ENST00000558320, ENST00000559182, ENST00000559237, ENST00000559352, ENST00000559446, ENST00000560002, ENST00000560121, ENST00000560298, ENST00000560388, ENST00000561126, ENST00000899813, ENST00000936365, ENST00000936366, ENST00000936367

RefSeq mRNA: 5 — MANE Select: NM_017661 NM_001002843, NM_001002844, NM_001288588, NM_001288589, NM_017661

CCDS: CCDS32245, CCDS42041, CCDS58364

Canonical transcript exons

ENST00000267807 — 22 exons

Exon	Start	End
ENSE00001408177	56733458	56733509
ENSE00001414286	56707082	56707150
ENSE00002570387	56630176	56632122
ENSE00003485840	56704121	56704267
ENSE00003625597	56654198	56654234
ENSE00003632417	56635195	56635250
ENSE00003670521	56642952	56642997
ENSE00003814454	56700933	56701072
ENSE00003814663	56666395	56666535
ENSE00003814789	56689041	56689150
ENSE00003816327	56678664	56678821
ENSE00003816414	56666679	56666986
ENSE00003816542	56701173	56701238
ENSE00003816873	56654385	56654503
ENSE00003817968	56676670	56676816
ENSE00003821695	56658424	56658486
ENSE00003822792	56693098	56693215
ENSE00003822800	56682254	56682477
ENSE00003823777	56677574	56677674
ENSE00003827013	56707263	56707306
ENSE00003827514	56689300	56689470
ENSE00003830925	56668823	56668957

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 98.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.0255 / max 286.2854, expressed in 1704 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150181	18.9173	1673
150183	4.9337	1425
150185	0.6187	361
150184	0.6164	369
207530	0.3455	169
150182	0.2600	115
150189	0.1728	80
150177	0.1262	32
150176	0.0349	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.35	gold quality
endocervix	UBERON:0000458	94.23	gold quality
adrenal tissue	UBERON:0018303	93.93	gold quality
mucosa of stomach	UBERON:0001199	93.44	gold quality
body of uterus	UBERON:0009853	93.40	gold quality
right ovary	UBERON:0002118	93.10	gold quality
left ovary	UBERON:0002119	92.91	gold quality
tibial nerve	UBERON:0001323	92.81	gold quality
right uterine tube	UBERON:0001302	92.74	gold quality
colonic epithelium	UBERON:0000397	92.65	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.51	gold quality
ectocervix	UBERON:0012249	92.40	gold quality
body of pancreas	UBERON:0001150	92.28	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.10	gold quality
lower esophagus	UBERON:0013473	92.06	gold quality
ganglionic eminence	UBERON:0004023	92.02	gold quality
minor salivary gland	UBERON:0001830	91.75	gold quality
left uterine tube	UBERON:0001303	91.66	gold quality
corpus callosum	UBERON:0002336	91.46	gold quality
cortical plate	UBERON:0005343	91.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.15	gold quality
cerebellar hemisphere	UBERON:0002245	91.10	gold quality
blood vessel layer	UBERON:0004797	91.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.03	gold quality
cerebellar cortex	UBERON:0002129	90.96	gold quality
ovary	UBERON:0000992	90.79	gold quality
popliteal artery	UBERON:0002250	90.72	gold quality
tibial artery	UBERON:0007610	90.72	gold quality
tendon	UBERON:0000043	90.60	gold quality
right coronary artery	UBERON:0001625	90.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

110 targeting ZNF280D, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-613	99.91	71.50	1710

Literature-anchored findings (GeneRIF, showing 1)

• As a first exploitation of this unique cohort, we identify three novel candidate dyslexia genes, ZNF280D and TCF12 at 15q21, and PDE7B at 6q23.3, by molecular mapping of the familial translocation with the 15q21 breakpoint. (PMID:20798984)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp280d	ENSMUSG00000038535
rattus_norvegicus	Zfp280d	ENSRNOG00000055631

Paralogs (28): ZNF280C (ENSG00000056277), ZBTB25 (ENSG00000089775), PRDM13 (ENSG00000112238), BCL6 (ENSG00000113916), FEZF1 (ENSG00000128610), ZBTB46 (ENSG00000130584), PRDM12 (ENSG00000130711), NACC2 (ENSG00000148411), FEZF2 (ENSG00000153266), ZBTB7B (ENSG00000160685), NACC1 (ENSG00000160877), BCL6B (ENSG00000161940), GFI1 (ENSG00000162676), GFI1B (ENSG00000165702), ZBTB49 (ENSG00000168826), ZNF280A (ENSG00000169548), ZNF581 (ENSG00000171425), ZNF524 (ENSG00000171443), ZBTB26 (ENSG00000171448), ZBTB21 (ENSG00000173276), ZNF683 (ENSG00000176083), ZBTB33 (ENSG00000177485), ZBTB3 (ENSG00000185670), ZBTB6 (ENSG00000186130), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF580 (ENSG00000213015), ZNF280B (ENSG00000275004)

Protein

Protein identifiers

Zinc finger protein 280D — Q6N043 (reviewed: Q6N043)

Alternative names: Suppressor of hairy wing homolog 4, Zinc finger protein 634

All UniProt accessions (3): Q6N043, H0YLA6, H0YN90

UniProt curated annotations — full annotation on UniProt →

Function. May function as a transcription factor.

Subcellular location. Nucleus.

Isoforms (6)

UniProt ID	Names	Canonical?
Q6N043-1	1	yes
Q6N043-2	2
Q6N043-3	3
Q6N043-4	4
Q6N043-5	5
Q6N043-6	6

RefSeq proteins (5): NP_001002843, NP_001002844, NP_001275517, NP_001275518, NP_060131* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR025243	DUF4195	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050527
IPR057618	Znf_POGZ/Z280C-D-like	Domain
IPR059074	Znf-C2H2_Z280C_D	Domain

Pfam: PF13836, PF25414, PF25429

UniProt features (60 total): cross-link 16, compositionally biased region 11, splice variant 9, zinc finger region 5, region of interest 5, sequence conflict 5, modified residue 4, sequence variant 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6N043-F1	56.08	0.12

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 (20): 104, 545, 908, 911, 32, 34, 74, 87, 126, 140, 189, 210, 223, 233, 275, 284, 292, 550, 740, 976

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, HUTTMANN_B_CLL_POOR_SURVIVAL_DN, MARTINEZ_RB1_TARGETS_DN, ACATTCC_MIR1_MIR206, ABBUD_LIF_SIGNALING_2_DN, AACATTC_MIR4093P, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, CHEN_HOXA5_TARGETS_9HR_UP, YOSHIMURA_MAPK8_TARGETS_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_TURQUOISE_DN, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, LU_EZH2_TARGETS_DN, SMIRNOV_RESPONSE_TO_IR_2HR_DN

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 (1): nucleus (GO:0005634)

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

Protein interactions and networks

STRING

1246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF280D	PHF20L1	A8MW92	467
ZNF280D	WDR70	Q9NW82	453
ZNF280D	ZGRF1	Q86YA3	447
ZNF280D	RNF216	Q9NWF9	440
ZNF280D	NPIPB8	E9PQR5	435
ZNF280D	CCDC184	Q52MB2	434
ZNF280D	NOP9	Q86U38	433
ZNF280D	OR8G1	Q15617	430
ZNF280D	SART1	O43290	423
ZNF280D	MCRIP2	Q9BUT9	419
ZNF280D	AFG1L	Q8WV93	416
ZNF280D	RPUSD3	Q6P087	414
ZNF280D	KDM5D	Q9BY66	404
ZNF280D	DTNBP1	Q96EV8	401
ZNF280D	OR51F1	A6NGY5	392

IntAct

13 interactions, top by confidence:

A	B	Type	Score
CBX1	ZNF292	psi-mi:“MI:0914”(association)	0.530
CBX5	ZNF568	psi-mi:“MI:0914”(association)	0.350
CBX3	KPNA4	psi-mi:“MI:0914”(association)	0.350
CBX1	EXOC5	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
	TTC8	psi-mi:“MI:0914”(association)	0.350
	PHF20L1	psi-mi:“MI:0914”(association)	0.350
CBX3	MYL12B	psi-mi:“MI:0914”(association)	0.350
CBX5	ZNF292	psi-mi:“MI:0914”(association)	0.350
ZMYM2	ZBTB5	psi-mi:“MI:2364”(proximity)	0.270
ZMYM3	TAF4	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (32): ZNF280D (Affinity Capture-MS), ZNF280D (Affinity Capture-MS), ZNF280D (Affinity Capture-MS), ZNF280D (Affinity Capture-MS), ZNF280D (Affinity Capture-MS), ZNF280D (Two-hybrid), ZNF280D (Two-hybrid), ZNF280D (Proximity Label-MS), CBX1 (Affinity Capture-MS), ZNF280D (Affinity Capture-MS), ZNF280D (Affinity Capture-MS), ZNF280D (Affinity Capture-MS), ZNF280D (Affinity Capture-MS), ZNF280D (Affinity Capture-MS), ZNF280D (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GR68, A2CG63, A2VE56, D3ZHS6, E6ZGB4, F7AQ22, O75376, O88974, P0C6S7, P57768, P57769, Q15047, Q2YDJ8, Q2YDW7, Q4KKX4, Q4LE39, Q52L14, Q5F3F2, Q5F3N6, Q5FWF5, Q5R6Q7, Q5VVJ2, Q60974, Q66JB6, Q68FE8, Q69Z61, Q69Z66, Q69Z69, Q6N043, Q6NXK2, Q7Z6G8, Q86YI8, Q8BIZ1, Q8C080, Q8K2W6, Q8QFX1, Q92560, Q96N64, Q98925, Q99PU7

Diamond homologs: P59817, Q5PPG4, Q68FE8, Q6N043, Q6P3Y5, Q7Z3K3, Q86YH2, Q8BZH4, Q8ND82, Q99KZ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	104
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4025 predictions. Top by Δscore:

Variant	Effect	Δscore
15:56632119:TTTA:T	acceptor_gain	1.0000
15:56632120:TTA:T	acceptor_gain	1.0000
15:56632121:TA:T	acceptor_gain	1.0000
15:56632123:C:CC	acceptor_gain	1.0000
15:56632123:CTGAA:C	acceptor_loss	1.0000
15:56642999:T:C	acceptor_gain	1.0000
15:56642999:T:TC	acceptor_gain	1.0000
15:56653499:T:A	donor_gain	1.0000
15:56653994:TTGA:T	donor_gain	1.0000
15:56666982:GTAAC:G	acceptor_gain	1.0000
15:56666987:C:CA	acceptor_loss	1.0000
15:56666987:C:CC	acceptor_gain	1.0000
15:56668817:A:C	donor_gain	1.0000
15:56668818:CTCA:C	donor_gain	1.0000
15:56668819:TCACT:T	donor_loss	1.0000
15:56668821:A:AC	donor_gain	1.0000
15:56668822:C:CT	donor_gain	1.0000
15:56668822:CT:C	donor_gain	1.0000
15:56668822:CTT:C	donor_gain	1.0000
15:56668822:CTTT:C	donor_gain	1.0000
15:56668822:CTTTT:C	donor_gain	1.0000
15:56668953:TTTTT:T	acceptor_gain	1.0000
15:56668954:TTTT:T	acceptor_gain	1.0000
15:56668955:TTT:T	acceptor_gain	1.0000
15:56668956:TT:T	acceptor_gain	1.0000
15:56668958:C:CA	acceptor_loss	1.0000
15:56668958:C:CC	acceptor_gain	1.0000
15:56668960:G:C	acceptor_gain	1.0000
15:56668961:T:TC	acceptor_gain	1.0000
15:56668962:T:C	acceptor_gain	1.0000

AlphaMissense

6543 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:56666426:A:G	C655R	1.000
15:56666453:A:G	C646R	1.000
15:56666979:A:C	I518S	1.000
15:56666979:A:G	I518T	1.000
15:56666979:A:T	I518N	1.000
15:56666985:A:T	V516D	1.000
15:56668839:A:G	L510S	1.000
15:56668848:A:G	L507P	1.000
15:56668848:A:T	L507Q	1.000
15:56668916:A:C	F484L	1.000
15:56668916:A:T	F484L	1.000
15:56668917:A:G	F484S	1.000
15:56668918:A:G	F484L	1.000
15:56668923:A:G	L482P	1.000
15:56668928:G:C	C480W	1.000
15:56668929:C:G	C480S	1.000
15:56668930:A:G	C480R	1.000
15:56668930:A:T	C480S	1.000
15:56668937:A:C	C477W	1.000
15:56668939:A:G	C477R	1.000
15:56676696:A:C	Y462D	1.000
15:56676724:G:C	C452W	1.000
15:56676725:C:T	C452Y	1.000
15:56676726:A:G	C452R	1.000
15:56676733:G:C	C449W	1.000
15:56676734:C:T	C449Y	1.000
15:56676735:A:G	C449R	1.000
15:56676740:A:G	L447S	1.000
15:56676770:A:G	F437S	1.000
15:56676813:A:G	C423R	1.000

dbSNP variants (sampled 300 via entrez): RS1000017458 (15:56714578 A>C), RS1000045104 (15:56673900 C>T), RS1000049994 (15:56714335 A>G), RS1000083120 (15:56684598 G>C,T), RS1000114549 (15:56637164 A>C,G), RS1000188778 (15:56636784 A>G), RS1000252931 (15:56719829 C>A,T), RS1000305016 (15:56687247 G>T), RS1000373202 (15:56725294 T>G), RS1000406006 (15:56725118 C>A,G), RS1000428014 (15:56687603 T>C), RS1000460024 (15:56630917 T>C), RS1000485571 (15:56679595 T>C), RS1000496932 (15:56679224 T>C), RS1000572703 (15:56635411 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004603_233	Platelet count	2.000000e-12
GCST004616_60	Platelet distribution width	2.000000e-10
GCST005830_110	Hand grip strength	3.000000e-11
GCST006065_27	Glaucoma (primary open-angle)	8.000000e-09
GCST006394_98	Intraocular pressure	6.000000e-10
GCST006412_89	Intraocular pressure	1.000000e-10
GCST008157_54	Body fat mass	3.000000e-06
GCST009725_57	Intraocular pressure	2.000000e-09
GCST010244_331	Triglyceride levels	4.000000e-14
GCST90002401_90	Platelet distribution width	1.000000e-14
GCST90002402_162	Platelet count	6.000000e-23

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007984	platelet component distribution width
EFO:0006941	grip strength measurement
EFO:0004695	intraocular pressure measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465321 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	4
sodium arsenite	decreases expression, increases abundance	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases methylation	1
trichostatin A	decreases expression	1
butyraldehyde	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
jinfukang	decreases expression	1
Leflunomide	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Clorgyline	increases expression	1
Succimer	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Lead	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	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
CHEMBL5342673	Binding	Degradation of ZFN280D in human TMD8 cells by measuring protein level at 111 nM for 6 hrs using label free proteomic analysis	Discovery of Novel Bruton’s Tyrosine Kinase PROTACs with Enhanced Selectivity and Cellular Efficacy. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XW29	HEK293 eGFP-ZNF280D	Transformed cell line	Female

Clinical trials (associated diseases)

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