ZNF491

Summary

ZNF491 (zinc finger protein 491, HGNC:23706) is a protein-coding gene on chromosome 19p13.2, encoding Zinc finger protein 491 (Q8N8L2). May be involved in transcriptional regulation.

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. Predicted to be active in nucleus.

Source: NCBI Gene 126069 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 75 total
• MANE Select transcript: NM_152356

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23706
Approved symbol	ZNF491
Name	zinc finger protein 491
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34791
Ensembl gene	ENSG00000177599
Ensembl biotype	protein_coding
Entrez	126069

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000323169, ENST00000450087, ENST00000479762, ENST00000492230, ENST00000931777, ENST00000967899, ENST00000967900

RefSeq mRNA: 1 — MANE Select: NM_152356 NM_152356

CCDS: CCDS12267

Canonical transcript exons

ENST00000323169 — 3 exons

Exon	Start	End
ENSE00001244744	11805947	11808503
ENSE00001417169	11804542	11804667
ENSE00001874659	11798523	11798727

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 79.02.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7522 / max 57.4145, expressed in 769 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173967	1.7522	769

Top tissues by expression

246 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	79.02	gold quality
ganglionic eminence	UBERON:0004023	78.11	gold quality
cortical plate	UBERON:0005343	76.23	gold quality
ventricular zone	UBERON:0003053	72.18	gold quality
right adrenal gland cortex	UBERON:0035827	71.95	gold quality
stromal cell of endometrium	CL:0002255	71.56	gold quality
right adrenal gland	UBERON:0001233	71.25	gold quality
cerebellar hemisphere	UBERON:0002245	70.36	gold quality
cerebellar cortex	UBERON:0002129	70.34	gold quality
left adrenal gland	UBERON:0001234	70.07	gold quality
left adrenal gland cortex	UBERON:0035825	70.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.47	gold quality
left ovary	UBERON:0002119	69.33	gold quality
descending thoracic aorta	UBERON:0002345	69.18	gold quality
apex of heart	UBERON:0002098	69.15	gold quality
smooth muscle tissue	UBERON:0001135	68.85	gold quality
right ovary	UBERON:0002118	68.42	gold quality
adrenal gland	UBERON:0002369	68.41	gold quality
adrenal cortex	UBERON:0001235	68.34	gold quality
cerebellum	UBERON:0002037	68.28	gold quality
islet of Langerhans	UBERON:0000006	67.94	gold quality
body of pancreas	UBERON:0001150	67.93	gold quality
muscle layer of sigmoid colon	UBERON:0035805	67.60	gold quality
colonic epithelium	UBERON:0000397	67.58	silver quality
right coronary artery	UBERON:0001625	67.35	gold quality
pancreas	UBERON:0001264	67.25	gold quality
body of uterus	UBERON:0009853	67.18	gold quality
rectum	UBERON:0001052	67.02	gold quality
calcaneal tendon	UBERON:0003701	67.01	gold quality
tibial artery	UBERON:0007610	66.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting ZNF491, 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-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-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-3667-3P	99.99	67.17	1636
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-4735-3P	99.14	69.85	777

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp78	ENSMUSG00000055150
rattus_norvegicus		ENSRNOG00000083797
drosophila_melanogaster	CG2712	FBGN0024975
drosophila_melanogaster	Phs	FBGN0036522
drosophila_melanogaster	CG3281	FBGN0260741

Paralogs (62): ZNF582 (ENSG00000018869), ZNF264 (ENSG00000083844), ZNF343 (ENSG00000088876), ZNF684 (ENSG00000117010), ZNF133 (ENSG00000125846), ZNF557 (ENSG00000130544), ZNF337 (ENSG00000130684), ZNF20 (ENSG00000132010), ZFP37 (ENSG00000136866), ZNF614 (ENSG00000142556), KRBOX4 (ENSG00000147121), ZNF599 (ENSG00000153896), ZNF19 (ENSG00000157429), ZNF589 (ENSG00000164048), PRDM9 (ENSG00000164256), ZNF180 (ENSG00000167384), ZNF558 (ENSG00000167785), ZNF35 (ENSG00000169981), ZNF778 (ENSG00000170100), ZNF439 (ENSG00000171291), ZNF440 (ENSG00000171295), ZNF556 (ENSG00000172000), ZNF554 (ENSG00000172006), ZNF596 (ENSG00000172748), ZNF80 (ENSG00000174255), ZNF266 (ENSG00000174652), ZNF25 (ENSG00000175395), ZNF77 (ENSG00000175691), ZNF169 (ENSG00000175787), ZNF404 (ENSG00000176222), ZNF620 (ENSG00000177842), ZNF619 (ENSG00000177873), ZNF875 (ENSG00000181666), ZNF329 (ENSG00000181894), ZFP90 (ENSG00000184939), ZNF566 (ENSG00000186017), ZNF529 (ENSG00000186020), ZNF749 (ENSG00000186230), ZNF555 (ENSG00000186300), ZNF70 (ENSG00000187792)

Protein

Protein identifiers

Zinc finger protein 491 — Q8N8L2 (reviewed: Q8N8L2)

All UniProt accessions (2): C9IYV0, Q8N8L2

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 (1): NP_689569* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (14 total): zinc finger region 13, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N8L2-F1	76.58	0.52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 35 (showing top): chr19p13, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, HMG20B_TARGET_GENES, ZNF274_TARGET_GENES, ZNF423_TARGET_GENES, ZNF597_TARGET_GENES, ZNF8_TARGET_GENES, MIR3658, MIR4297, MIR4705, MIR5581_5P, MIR6822_3P, GSE13485_CTRL_VS_DAY3_YF17D_VACCINE_PBMC_UP

GO Biological Process (1): regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (6): 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), 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
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	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
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

226 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF491	CWF19L2	Q2TBE0	479
ZNF491	KIAA0408	Q6ZU52	475
ZNF491	CAPN15	O75808	451
ZNF491	MED8	Q96G25	419
ZNF491	TFB2M	Q9H5Q4	413
ZNF491	ETV7	Q9Y603	410
ZNF491	ADGRF4	Q8IZF3	371
ZNF491	HTR3E	A5X5Y0	336
ZNF491	SPATA22	Q8NHS9	324
ZNF491	PLPP4	Q5VZY2	321
ZNF491	TAF1L	Q8IZX4	317
ZNF491	TMPRSS11A	Q6ZMR5	313
ZNF491	CCP110	O43303	302
ZNF491	J3KSM2	J3KSM2	298
ZNF491	ATOH8	Q96SQ7	279

IntAct

31 interactions, top by confidence:

A	B	Type	Score
KRTAP10-7	ZNF491	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	ZNF491	psi-mi:“MI:0915”(physical association)	0.560
ZNF491	MDFI	psi-mi:“MI:0915”(physical association)	0.560
ZNF491	CEP70	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	ZNF491	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	ZNF491	psi-mi:“MI:0915”(physical association)	0.560
ZNF491	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
CLK2	ZNF491	psi-mi:“MI:0915”(physical association)	0.560
ZNF491	CST4	psi-mi:“MI:0914”(association)	0.530
ZNF491	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.000
ZNF491	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.000
ZNF491	MDFI	psi-mi:“MI:0915”(physical association)	0.000
ZNF491	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.000
ZNF491	CEP70	psi-mi:“MI:0915”(physical association)	0.000
ZNF491	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
ZNF491	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
CLK2	ZNF491	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): BPIFA2 (Affinity Capture-MS), IGHA2 (Affinity Capture-MS), MUC7 (Affinity Capture-MS), CST2 (Affinity Capture-MS), IGJ (Affinity Capture-MS), PIGR (Affinity Capture-MS), CST4 (Affinity Capture-MS), ZG16B (Affinity Capture-MS), IGHA1 (Affinity Capture-MS), HIST2H2AB (Affinity Capture-MS), CST5 (Affinity Capture-MS), ZNF491 (Two-hybrid), ZNF491 (Two-hybrid), ZNF491 (Two-hybrid), KRTAP10-8 (Two-hybrid)

ESM2 similar proteins: A2RRD8, A6NHJ4, O43361, O95780, P0CB33, P15621, P16415, P17024, P51506, P51508, P52737, P52741, P58317, Q0D2J5, Q0VGE8, Q13360, Q13398, Q14584, Q147U1, Q15973, Q2M218, Q494X3, Q5HY98, Q5RBQ3, Q5REK1, Q5RES8, Q6P9A3, Q7L945, Q7Z340, Q8BZW4, Q8IW36, Q8IYI8, Q8N7K0, Q8N8L2, Q8N8Z8, Q8NDP4, Q8TA94, Q8TC21, Q96GE5, Q96I27

Diamond homologs: A0JPK3, A2RRD8, A2VDQ7, A3KN32, A8MUZ8, A8MWA4, C9JN71, E9QAG8, O60384, O60765, O75820, P0CH99, P0CI00, P10076, P10755, P15621, P16374, P16415, P17017, P17024, P51523, P52737, P52740, Q06730, Q06732, Q08AG5, Q0D2J5, Q13106, Q13360, Q15928, Q15935, Q15973, Q32M78, Q3KP31, Q4R4C7, Q4R6J4, Q4R882, Q5R9F0, Q5RC79, Q5REI6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

510 predictions. Top by Δscore:

Variant	Effect	Δscore
19:11798714:G:GT	donor_gain	0.9900
19:11798722:G:T	donor_gain	0.9900
19:11798753:A:G	donor_gain	0.9900
19:11805945:A:AG	acceptor_gain	0.9900
19:11805946:G:GG	acceptor_gain	0.9900
19:11805946:GA:G	acceptor_gain	0.9900
19:11805946:GAA:G	acceptor_gain	0.9900
19:11798728:G:GG	donor_gain	0.9800
19:11804527:T:G	acceptor_gain	0.9800
19:11798698:G:GT	donor_gain	0.9700
19:11798726:TGGT:T	donor_loss	0.9700
19:11798728:GTAA:G	donor_loss	0.9700
19:11798729:T:G	donor_loss	0.9700
19:11805941:TCACA:T	acceptor_loss	0.9700
19:11805942:CACAG:C	acceptor_loss	0.9700
19:11805943:ACAGA:A	acceptor_loss	0.9700
19:11805944:C:G	acceptor_gain	0.9700
19:11805944:CAG:C	acceptor_loss	0.9700
19:11805945:AGAAA:A	acceptor_loss	0.9700
19:11805946:G:GA	acceptor_loss	0.9700
19:11807818:T:A	acceptor_gain	0.9700
19:11804921:A:G	donor_gain	0.9600
19:11805946:GAAA:G	acceptor_gain	0.9600
19:11805006:A:AG	donor_gain	0.9500
19:11805946:GAAAT:G	acceptor_gain	0.9500
19:11798723:A:T	donor_gain	0.9400
19:11798766:GGGC:G	donor_gain	0.9400
19:11804526:ATGT:A	acceptor_gain	0.9400
19:11798721:G:GT	donor_gain	0.9300
19:11804525:C:G	acceptor_gain	0.9300

AlphaMissense

2926 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:11806623:T:C	F224L	0.963
19:11806625:C:A	F224L	0.963
19:11806625:C:G	F224L	0.963
19:11807127:T:C	F392L	0.963
19:11807129:C:A	F392L	0.963
19:11807129:C:G	F392L	0.963
19:11806539:T:C	F196L	0.961
19:11806541:C:A	F196L	0.961
19:11806541:C:G	F196L	0.961
19:11806455:T:C	F168L	0.959
19:11806457:C:A	F168L	0.959
19:11806457:C:G	F168L	0.959
19:11806875:T:C	F308L	0.958
19:11806877:C:A	F308L	0.958
19:11806877:C:G	F308L	0.958
19:11807211:T:C	F420L	0.958
19:11807213:C:A	F420L	0.958
19:11807213:C:G	F420L	0.958
19:11807043:T:C	F364L	0.949
19:11807045:T:A	F364L	0.949
19:11807045:T:G	F364L	0.949
19:11806791:T:C	F280L	0.947
19:11806793:T:A	F280L	0.947
19:11806793:T:G	F280L	0.947
19:11806959:T:C	F336L	0.935
19:11806961:C:A	F336L	0.935
19:11806961:C:G	F336L	0.935
19:11806580:C:A	H209Q	0.932
19:11806580:C:G	H209Q	0.932
19:11806832:C:A	H293Q	0.909

dbSNP variants (sampled 300 via entrez): RS1000256792 (19:11804489 C>T), RS1000390311 (19:11799272 A>C), RS1000416552 (19:11797973 T>A), RS1000442037 (19:11797687 C>T), RS1000574970 (19:11804436 A>G), RS1000620516 (19:11802943 T>G), RS1000639638 (19:11797502 T>C), RS1000701445 (19:11798994 C>T), RS1001107121 (19:11804164 C>T), RS1001151877 (19:11796543 G>A), RS1001236378 (19:11807199 T>A,C), RS1001800161 (19:11800863 A>C,G), RS1002077665 (19:11802294 A>G), RS1002775672 (19:11808398 G>A,C,T), RS1002860277 (19:11797381 C>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

2 associations (top):

Study	Trait	p-value
GCST004521_294	Autism spectrum disorder or schizophrenia	5.000000e-08
GCST009391_123	Metabolite levels	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010354	diacylglycerol 36:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
bisphenol A	increases expression	1
terbufos	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Fonofos	increases methylation	1
Lipopolysaccharides	decreases expression, decreases reaction	1
Parathion	increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Acrylamide	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_XW51	HEK293 eGFP-ZNF491	Transformed cell line	Female

Clinical trials (associated diseases)

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