ZNF678

Summary

ZNF678 (zinc finger protein 678, HGNC:28652) is a protein-coding gene on chromosome 1q42.13, encoding Zinc finger protein 678 (Q5SXM1). 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 DNA-templated transcription. Predicted to be located in nucleus.

Source: NCBI Gene 339500 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_001367909

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28652
Approved symbol	ZNF678
Name	zinc finger protein 678
Location	1q42.13
Locus type	gene with protein product
Status	Approved
Aliases	MGC42493
Ensembl gene	ENSG00000181450
Ensembl biotype	protein_coding
Entrez	339500

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000343776, ENST00000397097, ENST00000440339, ENST00000465266, ENST00000608949

RefSeq mRNA: 4 — MANE Select: NM_001367909 NM_001367909, NM_001367910, NM_001367911, NM_178549

CCDS: CCDS1560

Canonical transcript exons

ENST00000343776 — 4 exons

Exon	Start	End
ENSE00001815285	227654336	227662461
ENSE00003649351	227650956	227651076
ENSE00003664380	227646544	227646670
ENSE00003892175	227563556	227563724

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 83.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3094 / max 247.3891, expressed in 1589 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8899	8.9574	1582
8900	0.3520	166

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.97	gold quality
buccal mucosa cell	CL:0002336	83.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.99	gold quality
calcaneal tendon	UBERON:0003701	81.82	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.59	gold quality
ventricular zone	UBERON:0003053	80.61	gold quality
ganglionic eminence	UBERON:0004023	80.61	gold quality
cortical plate	UBERON:0005343	80.37	gold quality
corpus callosum	UBERON:0002336	80.11	gold quality
visceral pleura	UBERON:0002401	79.96	gold quality
trabecular bone tissue	UBERON:0002483	79.91	gold quality
islet of Langerhans	UBERON:0000006	79.75	gold quality
thymus	UBERON:0002370	79.24	gold quality
oviduct epithelium	UBERON:0004804	79.22	gold quality
epithelial cell of pancreas	CL:0000083	79.10	silver quality
colonic epithelium	UBERON:0000397	78.46	gold quality
secondary oocyte	CL:0000655	77.67	gold quality
adrenal tissue	UBERON:0018303	77.36	gold quality
parietal pleura	UBERON:0002400	77.29	gold quality
corpus epididymis	UBERON:0004359	76.83	gold quality
urethra	UBERON:0000057	76.63	gold quality
bone marrow cell	CL:0002092	76.45	gold quality
pylorus	UBERON:0001166	76.21	gold quality
mammary duct	UBERON:0001765	76.06	gold quality
epithelium of mammary gland	UBERON:0003244	76.03	gold quality
nipple	UBERON:0002030	75.89	gold quality
lower lobe of lung	UBERON:0008949	75.81	gold quality
tibia	UBERON:0000979	75.48	gold quality
endometrium	UBERON:0001295	75.45	gold quality
caput epididymis	UBERON:0004358	75.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.66

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2520.1	ZNF678	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605530

miRNA regulators (miRDB)

228 targeting ZNF678, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
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-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp738	ENSMUSG00000048280
mus_musculus	Zfp457	ENSMUSG00000055341
mus_musculus	Zfp595	ENSMUSG00000057842
mus_musculus	Zfp953	ENSMUSG00000098905
rattus_norvegicus	AABR07009105.1	ENSRNOG00000053325

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 678 — Q5SXM1 (reviewed: Q5SXM1)

All UniProt accessions (3): B1APK8, Q5SXM1, V9GYU6

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 (4): NP_001354838, NP_001354839, NP_001354840, NP_848644 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF13465, PF13912

UniProt features (19 total): zinc finger region 15, sequence variant 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SXM1-F1	76.20	0.43

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 86 (showing top): COATES_MACROPHAGE_M1_VS_M2_UP, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, TURASHVILI_BREAST_CARCINOMA_DUCTAL_VS_LOBULAR_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN, HORIUCHI_WTAP_TARGETS_UP, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, RATTENBACHER_BOUND_BY_CELF1, DURAND_STROMA_NS_UP, ZWANG_DOWN_BY_2ND_EGF_PULSE

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (5): 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), 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
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transition metal ion binding	1
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF678	ZFYVE28	Q9HCC9	674
ZNF678	RBM46	Q8TBY0	669
ZNF678	EXD3	Q8N9H8	669
ZNF678	BOLA3	Q53S33	507
ZNF678	C12orf60	Q5U649	446
ZNF678	STMP1	E0CX11	378
ZNF678	LRRC14B	A6NHZ5	371
ZNF678	PARD6G	Q9BYG4	348
ZNF678	SAP25	Q8TEE9	324
ZNF678	MFSD1	Q9H3U5	322
ZNF678	NBPF15	Q8N660	320
ZNF678	DYM	Q7RTS9	275
ZNF678	CCDC91	Q7Z6B0	270
ZNF678	TECTB	Q96PL2	269
ZNF678	NRBP1	Q9UHY1	263

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ECE1	ZNF678	psi-mi:“MI:0915”(physical association)	0.370
CBX5	ZNF292	psi-mi:“MI:0914”(association)	0.350
ezrA	ZNF678	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A2VDQ7, A6NNF4, A8MQ14, A8MTY0, E9QAG8, O75290, O75373, P08043, P0CJ79, P10751, P17017, P17027, P17039, P35789, P51522, P51523, Q08AN1, Q14585, Q14587, Q3SYV7, Q3ZCX4, Q4R4C7, Q52M93, Q5MCW4, Q5R5U3, Q5R8X1, Q5R9F0, Q5SXM1, Q6ECI4, Q6JLC9, Q6P3V2, Q6P5C7, Q6ZN57, Q86UE3, Q86XN6, Q86YE8, Q8C827, Q8IYB9, Q8N4W9, Q8N7M2

Diamond homologs: A0A1W2PQL4, A6NK75, A6NN14, A6NNF4, A6NP11, A8MTY0, A8MUV8, A8MXY4, B4DX44, B4DXR9, O14628, O43345, O75346, O75373, O75437, O95780, P0CB33, P0DKX0, P0DPD5, P17019, P17038, P35789, P52744, Q03923, Q03924, Q03936, Q03938, Q05481, Q14593, Q15928, Q3SXZ3, Q5JVG8, Q5SXM1, Q68DY1, Q6ZMV8, Q6ZN08, Q6ZR52, Q86V71, Q8IW36, Q8IYB9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1228 predictions. Top by Δscore:

Variant	Effect	Δscore
1:227654332:TCA:T	acceptor_loss	1.0000
1:227654334:A:AC	acceptor_loss	1.0000
1:227654334:A:AG	acceptor_gain	1.0000
1:227654335:G:GA	acceptor_gain	1.0000
1:227654335:GC:G	acceptor_gain	1.0000
1:227654335:GCT:G	acceptor_gain	1.0000
1:227654335:GCTA:G	acceptor_gain	1.0000
1:227654335:GCTAT:G	acceptor_gain	1.0000
1:227645668:A:T	donor_gain	0.9900
1:227646538:CCCCA:C	acceptor_loss	0.9900
1:227646539:CCCAG:C	acceptor_loss	0.9900
1:227646540:CCA:C	acceptor_loss	0.9900
1:227646541:CAG:C	acceptor_loss	0.9900
1:227646542:AG:A	acceptor_gain	0.9900
1:227646543:G:GC	acceptor_loss	0.9900
1:227646543:GG:G	acceptor_gain	0.9900
1:227563690:C:G	donor_gain	0.9800
1:227563722:ACGG:A	donor_loss	0.9800
1:227563723:CGGT:C	donor_loss	0.9800
1:227563724:GGTGA:G	donor_loss	0.9800
1:227563725:GTG:G	donor_loss	0.9800
1:227563726:T:TC	donor_loss	0.9800
1:227563727:GAGAG:G	donor_loss	0.9800
1:227646631:G:T	donor_gain	0.9800
1:227646667:CTGGG:C	donor_loss	0.9800
1:227646668:TGGG:T	donor_loss	0.9800
1:227646669:GGGTG:G	donor_loss	0.9800
1:227646671:G:A	donor_loss	0.9800
1:227646672:T:G	donor_loss	0.9800
1:227646673:G:GC	donor_loss	0.9800

AlphaMissense

3502 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:227654734:T:C	F162L	0.993
1:227654736:T:A	F162L	0.993
1:227654736:T:G	F162L	0.993
1:227654902:T:C	F218L	0.993
1:227654904:T:A	F218L	0.993
1:227654904:T:G	F218L	0.993
1:227654650:T:C	F134L	0.992
1:227654652:C:A	F134L	0.992
1:227654652:C:G	F134L	0.992
1:227654818:T:C	F190L	0.992
1:227654820:T:A	F190L	0.992
1:227654820:T:G	F190L	0.992
1:227654986:T:C	F246L	0.991
1:227654988:T:A	F246L	0.991
1:227654988:T:G	F246L	0.991
1:227654657:G:C	R136P	0.986
1:227655154:T:C	F302L	0.986
1:227655156:T:A	F302L	0.986
1:227655156:T:G	F302L	0.986
1:227655238:T:C	F330L	0.986
1:227655240:T:A	F330L	0.986
1:227655240:T:G	F330L	0.986
1:227655406:T:C	F386L	0.986
1:227655408:T:A	F386L	0.986
1:227655408:T:G	F386L	0.986
1:227654921:T:C	L224P	0.985
1:227655005:T:C	L252P	0.985
1:227654669:T:C	L140P	0.983
1:227654753:T:C	L168P	0.983
1:227655322:T:C	F358L	0.982

dbSNP variants (sampled 300 via entrez): RS1000005703 (1:227657618 G>A,T), RS1000040083 (1:227580696 A>G), RS1000041603 (1:227562068 A>G), RS1000128127 (1:227628080 G>A), RS1000157889 (1:227604294 C>G,T), RS1000162421 (1:227624212 C>A), RS1000182435 (1:227678201 G>T), RS1000207686 (1:227563384 G>A), RS1000222788 (1:227604726 T>G), RS1000238808 (1:227580108 C>T), RS1000249805 (1:227563940 C>T), RS1000312535 (1:227670887 G>A), RS1000345651 (1:227574364 T>C), RS1000383059 (1:227639680 G>A), RS1000396869 (1:227617491 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

19 associations (top):

Study	Trait	p-value
GCST000174_5	Height	5.000000e-09
GCST002647_17	Height	7.000000e-24
GCST002927_17	Mercury levels	2.000000e-06
GCST004067_31	Hip circumference adjusted for BMI	1.000000e-07
GCST004067_99	Hip circumference adjusted for BMI	8.000000e-10
GCST006976_105	Macular thickness	2.000000e-12
GCST007293_110	Body fat distribution (arm fat ratio)	3.000000e-09
GCST007293_4	Body fat distribution (arm fat ratio)	7.000000e-08
GCST007294_183	Body fat distribution (trunk fat ratio)	1.000000e-08
GCST007294_53	Body fat distribution (trunk fat ratio)	4.000000e-18
GCST007295_56	Body fat distribution (leg fat ratio)	4.000000e-11
GCST007327_153	Smoking status (ever vs never smokers)	6.000000e-09
GCST009186_1	Insular cortex volume	7.000000e-06
GCST009723_39	Vertical cup-disc ratio (adjusted for vertical disc diameter)	7.000000e-14
GCST009724_89	Vertical cup-disc ratio (multi-trait analysis)	3.000000e-16
GCST012226_431	Waist circumference adjusted for body mass index	1.000000e-09
GCST90007526_1	Low hand grip strength (60 years and older) (EWGSOP)	5.000000e-08
GCST90010718_1	Thumb osteoarthritis severity (hand Klsum)	2.000000e-13
GCST90020029_603	Waist circumference adjusted for body mass index	8.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0004341	body fat distribution
EFO:0004318	smoking behavior
EFO:0006939	cup-to-disc ratio measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0006941	grip strength measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	6
Phenylmercuric Acetate	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
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	increases expression, affects binding	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	increases expression, affects binding	1
Coumestrol	decreases expression	1
Endosulfan	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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