ZNF681

Summary

ZNF681 (zinc finger protein 681, HGNC:26457) is a protein-coding gene on chromosome 19p12, encoding Zinc finger protein 681 (Q96N22). May be involved in transcriptional regulation.

This gene encodes a protein containing the krueppel associated box (KRAB) and zinc-finger domains, which may be involved in transcriptional regulation. Non-functional alleles of this gene are present in alternate genome assemblies including T2T-CHM13v1.1, resulting from a ‘TG’ deletion (rs61397759) which causes a frameshift and a premature stop codon.

Source: NCBI Gene 148213 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_138286

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26457
Approved symbol	ZNF681
Name	zinc finger protein 681
Location	19p12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31526
Ensembl gene	ENSG00000196172
Ensembl biotype	protein_coding
Entrez	148213

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000402377, ENST00000528059, ENST00000531570, ENST00000887419

RefSeq mRNA: 1 — MANE Select: NM_138286 NM_138286

CCDS: CCDS12414

Canonical transcript exons

ENST00000402377 — 4 exons

Exon	Start	End
ENSE00001949113	23739195	23745323
ENSE00002246395	23755425	23755551
ENSE00002278565	23758747	23758891
ENSE00003590852	23754823	23754918

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 83.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.0464 / max 111.2585, expressed in 1127 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180281	3.4325	990
180280	1.6139	629

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.84	gold quality
ganglionic eminence	UBERON:0004023	79.44	gold quality
cortical plate	UBERON:0005343	78.97	gold quality
ventricular zone	UBERON:0003053	78.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.00	gold quality
adrenal tissue	UBERON:0018303	73.46	gold quality
calcaneal tendon	UBERON:0003701	71.79	gold quality
islet of Langerhans	UBERON:0000006	71.59	gold quality
upper leg skin	UBERON:0004262	68.75	gold quality
rectum	UBERON:0001052	66.54	gold quality
lymph node	UBERON:0000029	65.81	gold quality
cerebellar cortex	UBERON:0002129	64.37	gold quality
cerebellar hemisphere	UBERON:0002245	64.27	gold quality
prefrontal cortex	UBERON:0000451	64.22	gold quality
cerebellum	UBERON:0002037	63.56	gold quality
lower esophagus mucosa	UBERON:0035834	63.31	gold quality
smooth muscle tissue	UBERON:0001135	63.22	gold quality
bone marrow cell	CL:0002092	63.07	silver quality
pancreas	UBERON:0001264	63.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.82	gold quality
esophagus mucosa	UBERON:0002469	62.51	gold quality
stromal cell of endometrium	CL:0002255	61.61	gold quality
vermiform appendix	UBERON:0001154	61.52	gold quality
Brodmann (1909) area 9	UBERON:0013540	61.10	gold quality
tendon	UBERON:0000043	59.88	gold quality
skin of hip	UBERON:0001554	59.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	59.73	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	59.70	gold quality
tibia	UBERON:0000979	59.60	silver quality
thymus	UBERON:0002370	59.60	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

216 targeting ZNF681, 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-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-3688-3P	99.97	72.02	2834

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 681 — Q96N22 (reviewed: Q96N22)

All UniProt accessions (3): E9PJB6, E9PSC0, Q96N22

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96N22-1	1	yes
Q96N22-2	2

RefSeq proteins (1): NP_612143* (*=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
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF01352, PF13465

UniProt features (30 total): zinc finger region 16, sequence conflict 6, sequence variant 4, chain 1, domain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96N22-F1	66.83	0.08

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 71 (showing top): MODULE_205, chr19p12, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C, KIM_MYCN_AMPLIFICATION_TARGETS_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GTF2E2_TARGET_GENES, MIR616_5P, MIR371B_5P, MIR373_5P, MIR548AJ_3P_MIR548X_3P, MIR335_3P, MIR548AE_3P_MIR548AQ_3P, MIR548AH_3P_MIR548AM_3P, MIR548J_3P

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), 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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	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
regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF681	OR52N4	Q8NGI2	540
ZNF681	SYNGR4	O95473	471
ZNF681	TIGD7	Q6NT04	471
ZNF681	TIGD6	Q17RP2	446
ZNF681	ERVV-1	B6SEH8	438
ZNF681	RGPD3	A6NKT7	418
ZNF681	CRYBG2	Q8N1P7	393
ZNF681	NKAPL	Q5M9Q1	375
ZNF681	CGAS	Q8N884	348
ZNF681	KLK9	Q9UKQ9	348
ZNF681	RAB36	O95755	307
ZNF681	VEZT	Q9HBM0	291
ZNF681	ABCC12	Q96J65	289
ZNF681	KLK12	Q9UKR0	277
ZNF681	ACTB	P02570	277

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ECE1	ZNF681	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (1): ZNF681 (Affinity Capture-MS)

ESM2 similar proteins: A6NK75, A6NNF4, A6NP11, A8MTY0, B4DXR9, C9JN71, O75346, O75373, O75437, O95780, P0CJ79, P0DKX0, P0DPD5, P17017, P17019, P17035, P17038, P35789, Q03923, Q03924, Q03936, Q03938, Q08AN1, Q5MCW4, Q5R9F0, Q5SXM1, Q68DY1, Q6JLC9, Q6P5C7, Q6ZMV8, Q6ZN06, Q6ZN08, Q6ZNA1, Q6ZNG1, Q76KX8, Q86V71, Q86XN6, Q8IYB9, Q8IYN0, Q8N4W9

Diamond homologs: A0A1W2PQL4, A6NK75, A6NN14, A6NNF4, A6NP11, A8MQ14, A8MTY0, A8MUV8, A8MXY4, B4DX44, B4DXR9, E9PYI1, O14628, O43345, O75290, O75346, O75373, O75437, O95780, P0CB33, P0DKX0, P0DPD5, P16373, P17019, P17038, P21506, P35789, P52736, P52738, P52744, Q03923, Q03924, Q03936, Q03938, Q05481, Q14586, Q14593, Q14929, Q15928, Q3KNS6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

834 predictions. Top by Δscore:

Variant	Effect	Δscore
19:23745321:TAA:T	acceptor_gain	0.9900
19:23745324:C:CC	acceptor_gain	0.9900
19:23758742:CTCA:C	donor_loss	0.9900
19:23758743:TCAC:T	donor_loss	0.9900
19:23758744:CA:C	donor_loss	0.9900
19:23758745:ACCAT:A	donor_loss	0.9900
19:23758746:C:A	donor_loss	0.9900
19:23745320:ATAA:A	acceptor_gain	0.9800
19:23754927:T:TC	acceptor_gain	0.9800
19:23758741:TCTCA:T	donor_loss	0.9800
19:23745319:AATAA:A	acceptor_gain	0.9700
19:23754817:ACCT:A	donor_loss	0.9700
19:23754818:CCTA:C	donor_loss	0.9700
19:23754819:CTA:C	donor_loss	0.9700
19:23754820:TA:T	donor_loss	0.9700
19:23754821:ACC:A	donor_loss	0.9700
19:23754822:C:CG	donor_loss	0.9700
19:23754903:T:C	acceptor_gain	0.9700
19:23745213:A:C	donor_gain	0.9500
19:23755464:T:A	donor_gain	0.9500
19:23758745:A:AC	donor_gain	0.9500
19:23758746:C:CC	donor_gain	0.9500
19:23758780:G:C	donor_gain	0.9500
19:23745322:AAC:A	acceptor_loss	0.9400
19:23745323:ACTG:A	acceptor_loss	0.9400
19:23745324:CTGAA:C	acceptor_loss	0.9400
19:23754915:ATACC:A	acceptor_loss	0.9400
19:23754916:TACCT:T	acceptor_loss	0.9400
19:23754917:AC:A	acceptor_loss	0.9400
19:23754918:CC:C	acceptor_loss	0.9400

AlphaMissense

4313 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:23743837:A:C	F571L	0.983
19:23743837:A:T	F571L	0.983
19:23743839:A:G	F571L	0.983
19:23743753:A:C	F599L	0.973
19:23743753:A:T	F599L	0.973
19:23743755:A:G	F599L	0.973
19:23743921:A:C	F543L	0.973
19:23743921:A:T	F543L	0.973
19:23743923:A:G	F543L	0.973
19:23744425:A:C	F375L	0.973
19:23744425:A:T	F375L	0.973
19:23744427:A:G	F375L	0.973
19:23744509:A:C	F347L	0.970
19:23744509:A:T	F347L	0.970
19:23744511:A:G	F347L	0.970
19:23744089:A:C	F487L	0.966
19:23744089:A:T	F487L	0.966
19:23744091:A:G	F487L	0.966
19:23744005:G:C	F515L	0.956
19:23744005:G:T	F515L	0.956
19:23744007:A:G	F515L	0.956
19:23743832:T:G	Q573P	0.953
19:23744341:A:C	F403L	0.953
19:23744341:A:T	F403L	0.953
19:23744343:A:G	F403L	0.953
19:23755516:G:C	F13L	0.951
19:23755516:G:T	F13L	0.951
19:23755518:A:G	F13L	0.951
19:23744173:A:C	F459L	0.950
19:23744173:A:T	F459L	0.950

dbSNP variants (sampled 300 via entrez): RS1000055536 (19:23743283 C>T), RS1000160105 (19:23747279 A>T), RS1000191898 (19:23752338 C>A), RS1000250786 (19:23751671 T>C), RS1000331581 (19:23758561 G>A), RS1000586136 (19:23739275 A>G), RS1000849273 (19:23758071 G>A,T), RS1001130016 (19:23752502 A>G), RS1001420784 (19:23758244 A>G), RS1002143265 (19:23758687 G>A,C), RS1002163224 (19:23743932 C>T), RS1002195554 (19:23758861 G>A,C,T), RS1002224931 (19:23748951 C>CAA), RS1002336118 (19:23756077 G>T), RS1002446725 (19:23744983 T>C)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	decreases expression	1
hydroxyhydroquinone	decreases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Rosiglitazone	decreases reaction, increases expression	1
Pioglitazone	decreases reaction, increases expression	1
Troglitazone	decreases reaction, increases expression	1
Hydrogen Peroxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases expression	1
Vanadates	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	affects expression	1
Aflatoxin M1	decreases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1
tert-Butylhydroperoxide	decreases reaction, increases expression	1
Magnetite Nanoparticles	decreases expression	1

Clinical trials (associated diseases)

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