ZNF641

Summary

ZNF641 (zinc finger protein 641, HGNC:31834) is a protein-coding gene on chromosome 12q13.11, encoding Zinc finger protein 641 (Q96N77). Transcriptional activator.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol; nucleolus; and nucleoplasm.

Source: NCBI Gene 121274 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_001172681

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31834
Approved symbol	ZNF641
Name	zinc finger protein 641
Location	12q13.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31295
Ensembl gene	ENSG00000167528
Ensembl biotype	protein_coding
OMIM	613906
Entrez	121274

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 20 protein_coding, 1 retained_intron

ENST00000301042, ENST00000448928, ENST00000544117, ENST00000546874, ENST00000547026, ENST00000548932, ENST00000549125, ENST00000549512, ENST00000550181, ENST00000550342, ENST00000863439, ENST00000863440, ENST00000863441, ENST00000863442, ENST00000863443, ENST00000959280, ENST00000959281, ENST00000959282, ENST00000959283, ENST00000959284, ENST00000959285

RefSeq mRNA: 6 — MANE Select: NM_001172681 NM_001172681, NM_001172682, NM_001365803, NM_001365804, NM_001365805, NM_152320

CCDS: CCDS53787, CCDS53788, CCDS8763

Canonical transcript exons

ENST00000547026 — 6 exons

Exon	Start	End
ENSE00001113942	48345345	48345474
ENSE00001113945	48344599	48344712
ENSE00001113948	48347252	48347343
ENSE00002340914	48337180	48343727
ENSE00003604805	48347907	48348115
ENSE00003901094	48350786	48350919

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 95.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4929 / max 118.9985, expressed in 1619 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130730	6.4929	1619

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	95.56	gold quality
tibialis anterior	UBERON:0001385	94.13	silver quality
cardiac muscle of right atrium	UBERON:0003379	93.35	gold quality
adrenal tissue	UBERON:0018303	93.24	gold quality
left ventricle myocardium	UBERON:0006566	92.89	gold quality
kidney epithelium	UBERON:0004819	92.70	gold quality
epithelial cell of pancreas	CL:0000083	92.66	gold quality
ileal mucosa	UBERON:0000331	91.82	gold quality
deltoid	UBERON:0001476	91.82	gold quality
right adrenal gland cortex	UBERON:0035827	91.18	gold quality
adrenal cortex	UBERON:0001235	90.51	gold quality
right adrenal gland	UBERON:0001233	90.49	gold quality
adrenal gland	UBERON:0002369	90.14	gold quality
left adrenal gland cortex	UBERON:0035825	89.93	gold quality
left adrenal gland	UBERON:0001234	89.79	gold quality
blood	UBERON:0000178	89.64	gold quality
sperm	CL:0000019	89.07	gold quality
saphenous vein	UBERON:0007318	89.07	gold quality
monocyte	CL:0000576	88.88	gold quality
left ovary	UBERON:0002119	88.85	gold quality
leukocyte	CL:0000738	88.79	gold quality
palpebral conjunctiva	UBERON:0001812	88.73	gold quality
eye	UBERON:0000970	88.65	gold quality
cardia of stomach	UBERON:0001162	88.62	gold quality
granulocyte	CL:0000094	88.43	gold quality
pigmented layer of retina	UBERON:0001782	88.43	gold quality
ovary	UBERON:0000992	88.41	gold quality
pancreatic ductal cell	CL:0002079	88.31	gold quality
epithelium of nasopharynx	UBERON:0001951	88.07	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

100 targeting ZNF641, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-6126	99.62	68.09	996

Literature-anchored findings (GeneRIF, showing 1)

• HCG15 is a hypoxia-responsive lncRNA and facilitates hepatocellular carcinoma cell proliferation and invasion by enhancing ZNF641 transcription. (PMID:35427894)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	plagx	ENSDARG00000036855
danio_rerio	ovol1a	ENSDARG00000076472
danio_rerio	plagl2	ENSDARG00000076657
danio_rerio	ovol1b	ENSDARG00000078256
mus_musculus	Zfp641	ENSMUSG00000022987
rattus_norvegicus	Zfp641	ENSRNOG00000032447
drosophila_melanogaster	hb	FBGN0001180
drosophila_melanogaster	CG12391	FBGN0033581
caenorhabditis_elegans		WBGENE00001824
caenorhabditis_elegans		WBGENE00003033
caenorhabditis_elegans		WBGENE00012385

Paralogs (29): ZNF446 (ENSG00000083838), REST (ENSG00000084093), ZNF174 (ENSG00000103343), OVOL3 (ENSG00000105261), PLAGL1 (ENSG00000118495), ZSCAN18 (ENSG00000121413), ZNF576 (ENSG00000124444), OVOL2 (ENSG00000125850), PLAGL2 (ENSG00000126003), ZSCAN5A (ENSG00000131848), ZSCAN29 (ENSG00000140265), ZSCAN32 (ENSG00000140987), ZSCAN1 (ENSG00000152467), ZNF18 (ENSG00000154957), ZKSCAN2 (ENSG00000155592), ZNF496 (ENSG00000162714), ZNF202 (ENSG00000166261), ZNF444 (ENSG00000167685), SCAND1 (ENSG00000171222), ZNF274 (ENSG00000171606), ZNF131 (ENSG00000172262), OVOL1 (ENSG00000172818), ZNF518A (ENSG00000177853), ZNF518B (ENSG00000178163), PLAG1 (ENSG00000181690), ZSCAN5B (ENSG00000197213), ZNF770 (ENSG00000198146), PEG3 (ENSG00000198300), ZSCAN5C (ENSG00000204532)

Protein

Protein identifiers

Zinc finger protein 641 — Q96N77 (reviewed: Q96N77)

All UniProt accessions (6): Q96N77, F8VSM8, F8VXJ5, F8VZ73, F8VZV7, H0YHX6

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator. Activates transcriptional activities of SRE and AP-1.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in skeletal muscle, moderate expression in heart, liver, and pancreas, lower expression in placenta, no expression seen in brain, lung, and kidney.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96N77-1	1	yes
Q96N77-2	2
Q96N77-3	3
Q96N77-4	4

RefSeq proteins (6): NP_001166152, NP_001166153, NP_001352732, NP_001352733, NP_001352734, NP_689533 (=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

Pfam: PF00096, PF01352

UniProt features (23 total): zinc finger region 5, region of interest 4, compositionally biased region 3, splice variant 3, modified residue 2, sequence variant 2, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96N77-F1	49.35	0.00

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 (2): 191, 426

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 97 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GAANYNYGACNY_UNKNOWN, GOZGIT_ESR1_TARGETS_DN, CHANDRAN_METASTASIS_DN, YNGTTNNNATT_UNKNOWN, GOCC_NUCLEOLUS, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY

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 transcription regulatory region sequence-specific DNA binding (GO:0000977), 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 (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829)

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
nuclear lumen	2
cellular anatomical structure	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
transcription cis-regulatory region binding	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	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
intracellular membraneless organelle	1
cytoplasm	1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF641	OXNAD1	Q96HP4	560
ZNF641	EPB41L4B	Q9H329	498
ZNF641	CCDC74B	Q96LY2	446
ZNF641	CCDC169	A6NNP5	429
ZNF641	CCDC190	Q86UF4	427
ZNF641	GTPBP1	O00178	423
ZNF641	ZIM3	Q96PE6	399
ZNF641	CCDC125	Q86Z20	396
ZNF641	FBXL4	Q9UKA2	390
ZNF641	CENATAC	Q86UT8	375
ZNF641	POM121C	A8CG34	370
ZNF641	CCDC171	Q6TFL3	362
ZNF641	RALYL	Q86SE5	353
ZNF641	NSMAF	Q92636	346
ZNF641	KXD1	Q9BQD3	344

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ZNF641	ERO1B	psi-mi:“MI:0915”(physical association)	0.400
SQLE	ZNF641	psi-mi:“MI:0915”(physical association)	0.370
ZNF641	KDM1A	psi-mi:“MI:0915”(physical association)	0.370
ZNF641	TFAP2A	psi-mi:“MI:0915”(physical association)	0.370
ZNF641	ROCK2	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): ZNF641 (Reconstituted Complex), ZNF641 (Two-hybrid), ZNF641 (Two-hybrid), ZNF641 (Two-hybrid), ZNF641 (Two-hybrid), ZNF641 (Two-hybrid), MICAL1 (Affinity Capture-MS), CHAMP1 (Affinity Capture-MS), AHCYL2 (Affinity Capture-MS), RBM12 (Affinity Capture-MS), ROCK2 (Affinity Capture-MS), POGZ (Affinity Capture-MS), CSNK1G3 (Affinity Capture-MS), SRC (Affinity Capture-MS), ADD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5NS60, A0JN76, A1YFX5, A2T7G6, A6NJL1, D2HQI1, F1MJR8, O14901, P0CG00, P10754, P22227, P98182, Q0IJ29, Q1L8W0, Q3SWU4, Q5DW34, Q5EAC5, Q5EXX3, Q5RHB5, Q5SXI5, Q5T619, Q66H04, Q6NRM8, Q6NV66, Q6ZSB9, Q7M6U3, Q7TS63, Q7TSH3, Q7ZWZ4, Q801P1, Q86VK4, Q8BKX7, Q8BXX2, Q8NAM6, Q8NAP3, Q8NCP5, Q8R0A2, Q91VW9, Q96IT1, Q96N77

Diamond homologs: A6NFI3, A6NM28, A6QLU5, A7MBI1, A8MQ14, B4DU55, O43296, O75290, O75467, O95125, O95780, P0C7X2, P0DKX0, P15622, P17014, P17023, P17031, P17032, P17097, P21506, P51508, P51523, P51814, P52736, P52738, Q02525, Q06730, Q06732, Q08DG8, Q08ER8, Q14586, Q14929, Q16587, Q29RZ4, Q2M3X9, Q3ZCX4, Q49AA0, Q4V8A8, Q5CZA5, Q5FWF6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

956 predictions. Top by Δscore:

Variant	Effect	Δscore
12:48344593:TCTTA:T	donor_loss	1.0000
12:48344594:CTTA:C	donor_loss	1.0000
12:48344595:TTA:T	donor_loss	1.0000
12:48344596:TACC:T	donor_loss	1.0000
12:48344597:ACCT:A	donor_loss	1.0000
12:48344598:C:CA	donor_loss	1.0000
12:48344709:AATC:A	acceptor_gain	1.0000
12:48344710:ATC:A	acceptor_gain	1.0000
12:48344711:TC:T	acceptor_gain	1.0000
12:48344711:TCC:T	acceptor_loss	1.0000
12:48344712:CC:C	acceptor_gain	1.0000
12:48344712:CCTGC:C	acceptor_loss	1.0000
12:48344713:C:CA	acceptor_loss	1.0000
12:48344713:C:CC	acceptor_gain	1.0000
12:48344718:C:CT	acceptor_gain	1.0000
12:48344719:A:AC	acceptor_gain	1.0000
12:48344719:A:C	acceptor_gain	1.0000
12:48345276:AGC:A	donor_gain	1.0000
12:48345343:A:AC	donor_gain	1.0000
12:48345344:C:CC	donor_gain	1.0000
12:48345344:CT:C	donor_gain	1.0000
12:48345358:TATCC:T	donor_gain	1.0000
12:48345371:T:TA	donor_gain	1.0000
12:48345384:ATTCT:A	donor_gain	1.0000
12:48347339:CTGAG:C	acceptor_gain	1.0000
12:48347340:TGAG:T	acceptor_gain	1.0000
12:48347344:C:CC	acceptor_gain	1.0000
12:48347906:CCCTT:C	donor_gain	1.0000
12:48344708:AAATC:A	acceptor_gain	0.9900
12:48345298:T:TA	donor_gain	0.9900

AlphaMissense

2792 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:48343063:A:C	F409L	0.999
12:48343063:A:T	F409L	0.999
12:48343065:A:G	F409L	0.999
12:48343147:A:C	F381L	0.999
12:48343147:A:T	F381L	0.999
12:48343149:A:G	F381L	0.999
12:48343303:G:C	F329L	0.999
12:48343303:G:T	F329L	0.999
12:48343305:A:G	F329L	0.999
12:48343360:G:C	H310Q	0.999
12:48343360:G:T	H310Q	0.999
12:48343362:G:C	H310D	0.999
12:48343387:A:C	F301L	0.999
12:48343387:A:T	F301L	0.999
12:48343389:A:G	F301L	0.999
12:48343471:A:C	F273L	0.999
12:48343471:A:T	F273L	0.999
12:48343473:A:G	F273L	0.999
12:48343278:G:C	H338D	0.998
12:48343358:T:G	Q311P	0.998
12:48343362:G:T	H310N	0.998
12:48343370:A:G	L307P	0.998
12:48343444:A:C	H282Q	0.998
12:48343444:A:T	H282Q	0.998
12:48343446:G:C	H282D	0.998
12:48343446:G:T	H282N	0.998
12:48343036:G:C	H418Q	0.997
12:48343036:G:T	H418Q	0.997
12:48343108:G:C	H394Q	0.997
12:48343108:G:T	H394Q	0.997

dbSNP variants (sampled 300 via entrez): RS1000047341 (12:48337407 G>T), RS1000284313 (12:48350934 G>T), RS1000402264 (12:48344173 C>T), RS1000700910 (12:48345618 A>G), RS1000849780 (12:48344970 G>A), RS1000877476 (12:48349495 G>A), RS1000884848 (12:48352478 C>G,T), RS1001316982 (12:48352123 G>A), RS1001356602 (12:48342227 G>A,C), RS1001828268 (12:48347064 T>C,G), RS1001859272 (12:48346769 G>C), RS1001912836 (12:48352848 G>A), RS1002176556 (12:48338293 C>T), RS1002455737 (12:48335198 C>G), RS1002576339 (12:48342008 T>C)

Disease associations

OMIM: gene MIM:613906 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004601_162	Red blood cell count	1.000000e-17
GCST004604_56	Hematocrit	4.000000e-36
GCST004615_92	Hemoglobin concentration	8.000000e-29
GCST005051_22	Obstructive sleep apnea trait (apnea hypopnea index)	2.000000e-06
GCST005051_23	Obstructive sleep apnea trait (apnea hypopnea index)	4.000000e-07
GCST007876_118	Estimated glomerular filtration rate	2.000000e-09
GCST008058_111	Estimated glomerular filtration rate	2.000000e-17
GCST008059_10	Estimated glomerular filtration rate	4.000000e-16
GCST010083_235	Hemoglobin levels	7.000000e-49

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007817	sleep apnea measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Valproic Acid	decreases expression, decreases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
NSC 689534	affects binding, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Leflunomide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression	1
Cisplatin	increases expression	1
Copper	affects binding, increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Estradiol	affects expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XW71	HEK293 eGFP-ZNF641	Transformed cell line	Female

Clinical trials (associated diseases)

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