ZNF436

Summary

ZNF436 (zinc finger protein 436, HGNC:20814) is a protein-coding gene on chromosome 1p36.12, encoding Zinc finger protein 436 (Q9C0F3). May be a transcriptional repressor.

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 and nucleoplasm.

Source: NCBI Gene 80818 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_001077195

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20814
Approved symbol	ZNF436
Name	zinc finger protein 436
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1710, Zfp46
Ensembl gene	ENSG00000125945
Ensembl biotype	protein_coding
OMIM	611703
Entrez	80818

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000314011, ENST00000374608, ENST00000711404

RefSeq mRNA: 3 — MANE Select: NM_001077195 NM_001077195, NM_001370652, NM_030634

CCDS: CCDS233

Canonical transcript exons

ENST00000314011 — 4 exons

Exon	Start	End
ENSE00000908701	23367042	23367168
ENSE00000955857	23369366	23369836
ENSE00000955858	23367973	23368065
ENSE00001271814	23359448	23363221

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 91.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.0311 / max 635.5076, expressed in 1744 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10963	3.0759	1409
10964	2.6464	837
10962	1.3586	920
10965	1.2088	325
10966	0.7821	340
10961	0.7642	416
10960	0.1950	93

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	91.02	gold quality
endometrium	UBERON:0001295	88.45	gold quality
adrenal tissue	UBERON:0018303	87.65	gold quality
calcaneal tendon	UBERON:0003701	85.82	gold quality
corpus callosum	UBERON:0002336	85.03	gold quality
embryo	UBERON:0000922	84.99	gold quality
ganglionic eminence	UBERON:0004023	84.99	gold quality
right adrenal gland	UBERON:0001233	84.34	gold quality
smooth muscle tissue	UBERON:0001135	83.83	gold quality
esophagus mucosa	UBERON:0002469	83.65	gold quality
left adrenal gland	UBERON:0001234	83.48	gold quality
adrenal gland	UBERON:0002369	83.41	gold quality
lower esophagus mucosa	UBERON:0035834	83.28	gold quality
gall bladder	UBERON:0002110	82.90	gold quality
ovary	UBERON:0000992	82.87	gold quality
left ovary	UBERON:0002119	82.87	gold quality
minor salivary gland	UBERON:0001830	82.42	gold quality
ventricular zone	UBERON:0003053	82.40	gold quality
saliva-secreting gland	UBERON:0001044	82.04	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.92	gold quality
right adrenal gland cortex	UBERON:0035827	81.74	gold quality
prefrontal cortex	UBERON:0000451	81.64	gold quality
left adrenal gland cortex	UBERON:0035825	81.56	gold quality
urinary bladder	UBERON:0001255	81.51	gold quality
uterus	UBERON:0000995	81.40	gold quality
skin of abdomen	UBERON:0001416	81.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.29	gold quality
zone of skin	UBERON:0000014	81.09	gold quality
esophagus	UBERON:0001043	81.08	gold quality
mammary gland	UBERON:0001911	80.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.83

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
CDH17
KRT27
ME3
PSEN1
RNF114
SMARCA4
SNCA
TNFRSF11A
TRIM28

JASPAR motifs

Motif	Name	Family
MA2494.1	ZNF436	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605368

miRNA regulators (miRDB)

114 targeting ZNF436, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4482-3P	99.98	72.50	3147
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-4666A-3P	99.96	71.71	3434
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3133	99.81	70.92	3506

Literature-anchored findings (GeneRIF, showing 4)

• ZNF436 is a member of the zinc finger transcription factor family and may act as a negative regulator in gene transcription mediated by the MAPK signaling pathways. (PMID:17089209)
• ZNF436 has a role in promoting tumor cell proliferation through transcriptional activation of BCL10 in glioma (PMID:31178130)
• MicroRNA-4317 suppresses the progression of hepatocellular carcinoma by targeting ZNF436-mediated PI3K/AKT signaling pathway. (PMID:34861581)
• Chromosome 1p36 candidate gene ZNF436 predicts the prognosis of neuroblastoma: a bioinformatic analysis. (PMID:37904225)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp46	ENSMUSG00000051351

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), 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), ZNF3 (ENSG00000166526)

Protein

Protein identifiers

Zinc finger protein 436 — Q9C0F3 (reviewed: Q9C0F3)

All UniProt accessions (2): Q9C0F3, A0AAA9YHR6

UniProt curated annotations — full annotation on UniProt →

Function. May be a transcriptional repressor.

Subcellular location. Nucleus.

Tissue specificity. Expressed in fetal brain, heart, liver, spleen, bladder, lung, skin, skeletal muscle, stomach and pancreas.

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

RefSeq proteins (3): NP_001070663, NP_001357581, NP_085137 (=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 (18 total): zinc finger region 12, chain 1, domain 1, region of interest 1, compositionally biased region 1, cross-link 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0F3-F1	77.81	0.56

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 (1): 66

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 168 (showing top): RRAGTTGT_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, HNF3ALPHA_Q6, PEREZ_TP63_TARGETS, SP3_Q3, GGGTGGRR_PAX4_03, COUP_01, NFKB_C, NKX62_Q2, AP1_Q4_01, NF1_Q6_01, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, HNF4_DR1_Q3, TGANTCA_AP1_C, AACTTT_UNKNOWN

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

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 (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), 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
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
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

1940 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF436	TRIM28	Q13263	981
ZNF436	ZUP1	Q96AP4	855
ZNF436	USP5	P45974	819
ZNF436	UBB	P02248	810
ZNF436	YOD1	Q5VVQ6	788
ZNF436	USP44	Q9H0E7	773
ZNF436	OTUD7A	Q8TE49	739
ZNF436	SETDB1	Q15047	673
ZNF436	ZPR1	O75312	670
ZNF436	CRBN	Q96SW2	660
ZNF436	HDAC6	Q9UBN7	653
ZNF436	UBA2	Q9UBT2	646
ZNF436	PHF20	Q9BVI0	638
ZNF436	NPLOC4	Q8TAT6	567
ZNF436	ZFAND5	O76080	554

IntAct

98 interactions, top by confidence:

A	B	Type	Score
PIBF1	ZNF436	psi-mi:“MI:0915”(physical association)	0.560
ENKD1	ZNF436	psi-mi:“MI:0915”(physical association)	0.560
BYSL	ZNF436	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	ZNF436	psi-mi:“MI:0915”(physical association)	0.560
CCDC125	ZNF436	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	ZNF580	psi-mi:“MI:0915”(physical association)	0.560
CLK2	ZNF436	psi-mi:“MI:0915”(physical association)	0.560
CCDC57	ZNF436	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	KIF9	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	DMWD	psi-mi:“MI:0915”(physical association)	0.560
ZNF436		psi-mi:“MI:0915”(physical association)	0.560
ZNF436	ELAVL4	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	GFAP	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	GSN	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	HRAS	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	LMNA	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	NEFL	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	NF2	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	WFS1	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	JPH3	psi-mi:“MI:0915”(physical association)	0.560
ZNF436	SPRED1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (21): ZNF436 (Affinity Capture-MS), ZNF436 (Affinity Capture-RNA), ZNF436 (Two-hybrid), WDYHV1 (Two-hybrid), CCDC57 (Two-hybrid), CLK2 (Two-hybrid), CCDC125 (Two-hybrid), ZNF580 (Two-hybrid), ZNF436 (Affinity Capture-MS), ZNF436 (Two-hybrid), ZNF436 (Two-hybrid), ZNF436 (Reconstituted Complex), ECT2L (Affinity Capture-MS), PNLIPRP2 (Affinity Capture-MS), ZNF436 (Affinity Capture-RNA)

ESM2 similar proteins: A6QLU5, O75820, P08043, P10076, P10755, P16374, P16415, P17014, P17021, P17027, P17039, P51786, Q08AN1, Q14588, Q3KP31, Q3ZCX4, Q52M93, Q5MCW4, Q5R5Q6, Q5R5S6, Q5R5Y7, Q5RB30, Q5REA0, Q5REI6, Q6P3V2, Q6P9Y7, Q6ZNA1, Q7TSH9, Q7TSI0, Q7Z3V5, Q80W31, Q86UE3, Q86YE8, Q8BPP0, Q8N141, Q8N4W9, Q8N9F8, Q8NDQ6, Q8TBZ5, Q96ND8

Diamond homologs: A0A1W2PQL4, A2RRD8, A2VDP4, A2VDQ7, A8MQ14, A8MTY0, A8MUV8, B4DX44, B4DXR9, C9JN71, E9PW05, O75290, O75346, O75820, P0CH99, P0CI00, P0CJ79, P0DKX0, P10755, P15622, P16373, P16374, P17030, P17035, P35789, P52738, Q147U1, Q32M78, Q3KNS6, Q3MIS6, Q494X3, Q4R6C2, Q4R6J4, Q5HY98, Q5HYK9, Q5JVG8, Q5R5Q6, Q5R5S6, Q5R5Y7, Q5REA0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

474 predictions. Top by Δscore:

Variant	Effect	Δscore
1:23367037:CTTA:C	donor_gain	1.0000
1:23367039:TA:T	donor_loss	1.0000
1:23367040:A:AC	donor_gain	1.0000
1:23367040:AC:A	donor_gain	1.0000
1:23367041:C:CA	donor_gain	1.0000
1:23367041:CC:C	donor_gain	1.0000
1:23367041:CCT:C	donor_gain	1.0000
1:23367041:CCTA:C	donor_gain	1.0000
1:23367041:CCTAG:C	donor_gain	1.0000
1:23369362:TTA:T	donor_loss	1.0000
1:23369363:TACCT:T	donor_loss	1.0000
1:23369364:A:AC	donor_gain	1.0000
1:23369364:ACC:A	donor_loss	1.0000
1:23369364:ACCT:A	donor_gain	1.0000
1:23369365:C:CC	donor_gain	1.0000
1:23369365:CCTC:C	donor_gain	1.0000
1:23363219:AATC:A	acceptor_loss	0.9900
1:23363220:ATCT:A	acceptor_loss	0.9900
1:23363221:TCT:T	acceptor_loss	0.9900
1:23363222:C:CC	acceptor_gain	0.9900
1:23367036:A:AC	donor_gain	0.9900
1:23367037:C:CC	donor_gain	0.9900
1:23367038:TTACC:T	donor_gain	0.9900
1:23367039:TACC:T	donor_gain	0.9900
1:23367040:ACCTA:A	donor_gain	0.9900
1:23367169:C:CC	acceptor_gain	0.9900
1:23367169:CTG:C	acceptor_loss	0.9900
1:23367170:T:A	acceptor_loss	0.9900
1:23368061:CAGCG:C	acceptor_gain	0.9900
1:23369365:CCT:C	donor_gain	0.9900

AlphaMissense

3160 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:23362605:G:C	F259L	0.999
1:23362605:G:T	F259L	0.999
1:23362607:A:G	F259L	0.999
1:23362672:A:G	L237P	0.999
1:23362689:G:C	F231L	0.999
1:23362689:G:T	F231L	0.999
1:23362691:A:G	F231L	0.999
1:23362773:A:C	F203L	0.999
1:23362773:A:T	F203L	0.999
1:23362775:A:G	F203L	0.999
1:23362857:G:C	F175L	0.999
1:23362857:G:T	F175L	0.999
1:23362859:A:G	F175L	0.999
1:23362101:G:C	F427L	0.998
1:23362101:G:T	F427L	0.998
1:23362103:A:G	F427L	0.998
1:23362269:G:C	F371L	0.998
1:23362269:G:T	F371L	0.998
1:23362271:A:G	F371L	0.998
1:23362521:G:C	F287L	0.998
1:23362521:G:T	F287L	0.998
1:23362523:A:G	F287L	0.998
1:23362588:A:G	L265P	0.998
1:23362662:G:C	H240Q	0.998
1:23362662:G:T	H240Q	0.998
1:23362185:A:C	F399L	0.997
1:23362185:A:T	F399L	0.997
1:23362187:A:G	F399L	0.997
1:23362504:A:G	L293P	0.997
1:23362576:T:G	Q269P	0.997

dbSNP variants (sampled 300 via entrez): RS1000373698 (1:23362143 T>C), RS1000489867 (1:23361763 A>G), RS1000557919 (1:23368497 C>G,T), RS1000669000 (1:23360327 T>A), RS1000702933 (1:23368136 T>C), RS1000724348 (1:23367878 T>A), RS1000844257 (1:23368750 A>G), RS1001158727 (1:23365606 C>T), RS1001675912 (1:23371658 C>T), RS1002047627 (1:23360630 T>C), RS1002115129 (1:23367712 T>C), RS1002142562 (1:23360359 T>C), RS1002658930 (1:23370402 C>T), RS1003254820 (1:23369183 G>C), RS1003337543 (1:23368294 G>A,C)

Disease associations

OMIM: gene MIM:611703 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005984_1	Glomerular filtration rate	5.000000e-12
GCST006979_866	Heel bone mineral density	1.000000e-11
GCST007344_85	Estimated glomerular filtration rate	5.000000e-13
GCST007876_64	Estimated glomerular filtration rate	8.000000e-15
GCST90020024_10	A body shape index	9.000000e-09
GCST90020027_1780	Waist-hip index	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
bisphenol A	affects cotreatment, increases methylation, increases expression	3
trichostatin A	affects cotreatment, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Formaldehyde	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
cupric oxide	increases expression	1
vanadyl sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	decreases methylation	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Arsenic	affects methylation	1
Carbamazepine	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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