ZNF416

Summary

ZNF416 (zinc finger protein 416, HGNC:20645) is a protein-coding gene on chromosome 19q13.43, encoding Zinc finger protein 416 (Q9BWM5). Acts as a mechanosensitive transcriptional activator in fibroblasts, regulating the expression of genes involved in proliferation, extracellular matrix synthesis, and contractility in response to increased matrix stiffness.

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 microautophagy; regulation of proteasomal ubiquitin-dependent protein catabolic process; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within cardiac muscle hypertrophy; negative regulation of cell growth involved in cardiac muscle cell development; and negative regulation of protein phosphorylation. Predicted to be active in nucleus.

Source: NCBI Gene 55659 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_017879

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20645
Approved symbol	ZNF416
Name	zinc finger protein 416
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20557
Ensembl gene	ENSG00000083817
Ensembl biotype	protein_coding
OMIM	621253
Entrez	55659

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000196489, ENST00000896581

RefSeq mRNA: 2 — MANE Select: NM_017879 NM_001353405, NM_017879

CCDS: CCDS12954

Canonical transcript exons

ENST00000196489 — 4 exons

Exon	Start	End
ENSE00000822470	57571566	57573701
ENSE00002486368	57578057	57578098
ENSE00002512850	57575804	57575930
ENSE00002704068	57578672	57578911

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 90.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.7018 / max 54.2742, expressed in 1631 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182910	4.7018	1631

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	90.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.57	gold quality
esophagus squamous epithelium	UBERON:0006920	77.66	gold quality
cardiac muscle of right atrium	UBERON:0003379	76.99	gold quality
left ventricle myocardium	UBERON:0006566	76.90	gold quality
ventricular zone	UBERON:0003053	75.78	gold quality
cortical plate	UBERON:0005343	75.20	gold quality
embryo	UBERON:0000922	74.18	gold quality
ganglionic eminence	UBERON:0004023	74.18	gold quality
islet of Langerhans	UBERON:0000006	74.13	gold quality
stromal cell of endometrium	CL:0002255	73.76	gold quality
upper arm skin	UBERON:0004263	73.17	gold quality
skin of leg	UBERON:0001511	72.92	gold quality
oocyte	CL:0000023	72.87	gold quality
nasal cavity epithelium	UBERON:0005384	72.60	gold quality
germinal epithelium of ovary	UBERON:0001304	72.38	silver quality
myocardium	UBERON:0002349	71.92	gold quality
granulocyte	CL:0000094	71.87	gold quality
skin of abdomen	UBERON:0001416	71.83	gold quality
smooth muscle tissue	UBERON:0001135	71.65	gold quality
zone of skin	UBERON:0000014	71.60	gold quality
palpebral conjunctiva	UBERON:0001812	70.82	gold quality
calcaneal tendon	UBERON:0003701	70.32	gold quality
esophagus mucosa	UBERON:0002469	70.14	gold quality
muscle of leg	UBERON:0001383	70.03	gold quality
amniotic fluid	UBERON:0000173	70.02	gold quality
gastrocnemius	UBERON:0001388	69.97	gold quality
gingival epithelium	UBERON:0001949	69.91	silver quality
heart right ventricle	UBERON:0002080	69.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting ZNF416, 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-570-3P	99.96	72.41	4910
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-147A	98.33	66.40	795
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-4750-3P	96.65	64.38	512
HSA-MIR-601	95.98	67.59	421
HSA-MIR-10401-3P	91.66	66.01	97

Cross-species orthologs

0 orthologs

Paralogs (51): WIZ (ENSG00000011451), MYNN (ENSG00000085274), PRDM4 (ENSG00000110851), PRDM2 (ENSG00000116731), ZBTB17 (ENSG00000116809), ZNF644 (ENSG00000122482), GZF1 (ENSG00000125812), ZNF426 (ENSG00000130818), ZNF287 (ENSG00000141040), ZNF697 (ENSG00000143067), ZNF687 (ENSG00000143373), ZNF214 (ENSG00000149050), ZNF547 (ENSG00000152433), ZNF776 (ENSG00000152443), ZNF230 (ENSG00000159882), ZNF222 (ENSG00000159885), ZNF233 (ENSG00000159915), ZNF333 (ENSG00000160961), ZNF319 (ENSG00000166188), ZNF592 (ENSG00000166716), ZNF646 (ENSG00000167395), ZNF507 (ENSG00000168813), ZNF768 (ENSG00000169957), ZNF417 (ENSG00000173480), ZNF408 (ENSG00000175213), ZBTB41 (ENSG00000177888), ZNF223 (ENSG00000178386), ZNF852 (ENSG00000178917), ZNF784 (ENSG00000179922), ZNF572 (ENSG00000180938), ZNF707 (ENSG00000181135), ZNF746 (ENSG00000181220), ZNF467 (ENSG00000181444), ZNF530 (ENSG00000183647), ZNF17 (ENSG00000186272), ZNF527 (ENSG00000189164), ZKSCAN7 (ENSG00000196345), ZNF34 (ENSG00000196378), ZNF774 (ENSG00000196391), ZNF777 (ENSG00000196453)

Protein

Protein identifiers

Zinc finger protein 416 — Q9BWM5 (reviewed: Q9BWM5)

All UniProt accessions (1): Q9BWM5

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a mechanosensitive transcriptional activator in fibroblasts, regulating the expression of genes involved in proliferation, extracellular matrix synthesis, and contractility in response to increased matrix stiffness.

Subcellular location. Nucleus.

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

RefSeq proteins (2): NP_001340334, NP_060349* (*=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

UniProt features (17 total): zinc finger region 12, chain 1, domain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWM5-F1	63.72	0.20

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 42 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_FIBROBLAST_PROLIFERATION, GOBP_FIBROBLAST_ACTIVATION, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, KUMAR_AUTOPHAGY_NETWORK, GOMF_DNA_BINDING_TRANSCRIPTION_ACTIVATOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ARID5B_TARGET_GENES, BANP_TARGET_GENES, CEBPZ_TARGET_GENES, HMG20B_TARGET_GENES, ZFP91_TARGET_GENES, ZNF350_TARGET_GENES, MIR141_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

424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF416	EP300	Q09472	431
ZNF416	MAGEE2	Q8TD90	366
ZNF416	PUS7L	Q9H0K6	348
ZNF416	NWD1	Q149M9	315
ZNF416	LY6G5C	Q5SRR4	301
ZNF416	KCNF1	Q9H3M0	299
ZNF416	GBX1	Q14549	270
ZNF416	DMRTA2	Q96SC8	268
ZNF416	TEAD2	Q15562	267
ZNF416	RNF39	Q9H2S5	257
ZNF416	TFAP4	Q01664	236
ZNF416	TRIM37	O94972	233
ZNF416	POU6F2	P78424	232
ZNF416	TEAD4	Q15561	222
ZNF416	MPZL2	O60487	220

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ZNF416	PGK2	psi-mi:“MI:0914”(association)	0.530
ZNF416		psi-mi:“MI:0914”(association)	0.350
ZNF416	TRIM24	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): PGK2 (Affinity Capture-MS), TRIM39 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), TRIM37 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), CENPB (Affinity Capture-MS), ZNF211 (Affinity Capture-MS), ZNF416 (Affinity Capture-RNA), TRIM39 (Affinity Capture-MS), PGK2 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), ZNF211 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS)

ESM2 similar proteins: A0JNB1, A1YF12, A1YG88, A2T759, A3KN32, B2RUI1, O43296, O75123, P10072, P17020, P17097, P51814, P52736, P52740, Q07230, Q08ER8, Q13398, Q14590, Q32KN0, Q3KQV3, Q3MIS6, Q4V8A8, Q5CZA5, Q5RBQ3, Q5RBX0, Q5RCD9, Q5RCX4, Q6GQR8, Q6NX45, Q6P9A3, Q6PK81, Q7TSH9, Q7TSI0, Q7Z7L9, Q86UD4, Q8BFS8, Q8BLB0, Q8IVP9, Q8IZ26, Q8N9F8

Diamond homologs: A2RRD8, A6NFI3, A6NM28, A8MUZ8, A8MWA4, B2RUI1, B4DU55, E9Q8G5, O43296, O43361, O75467, O75820, P0CH99, P0CI00, P10078, P16373, P16374, P17021, P17023, P17032, P17097, P17098, P21506, P51786, P52740, Q06732, Q08ER8, Q13106, Q13360, Q13398, Q14592, Q147U1, Q32M78, Q3KQV3, Q3MIS6, Q3SY52, Q571J5, Q5CZA5, Q5HY98, Q5R7I8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

635 predictions. Top by Δscore:

Variant	Effect	Δscore
19:57573698:CAAA:C	acceptor_gain	1.0000
19:57573702:C:CC	acceptor_gain	1.0000
19:57573697:ACAAA:A	acceptor_gain	0.9900
19:57573698:CAAAC:C	acceptor_gain	0.9900
19:57573699:AAA:A	acceptor_gain	0.9900
19:57573701:ACTG:A	acceptor_loss	0.9900
19:57573703:T:G	acceptor_loss	0.9900
19:57575797:GCCTT:G	donor_loss	0.9900
19:57575798:CCTT:C	donor_loss	0.9900
19:57575799:CTT:C	donor_loss	0.9900
19:57575800:TTACC:T	donor_loss	0.9900
19:57575801:TACCC:T	donor_loss	0.9900
19:57575802:A:AC	donor_gain	0.9900
19:57575802:A:C	donor_loss	0.9900
19:57575802:AC:A	donor_gain	0.9900
19:57575803:C:CC	donor_gain	0.9900
19:57575803:CC:C	donor_gain	0.9900
19:57575803:CCCAG:C	donor_gain	0.9900
19:57575926:CAGCC:C	acceptor_gain	0.9900
19:57575935:CATGA:C	acceptor_gain	0.9900
19:57578053:TCACC:T	donor_loss	0.9900
19:57578054:CA:C	donor_loss	0.9900
19:57578055:A:T	donor_loss	0.9900
19:57578056:C:CG	donor_loss	0.9900
19:57578562:AGT:A	donor_gain	0.9900
19:57575279:TGGG:T	donor_gain	0.9800
19:57575935:C:T	acceptor_gain	0.9800
19:57578095:GAACC:G	acceptor_loss	0.9800
19:57578096:AACCT:A	acceptor_loss	0.9800
19:57578097:ACC:A	acceptor_loss	0.9800

AlphaMissense

3972 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:57572227:A:C	F559L	0.998
19:57572227:A:T	F559L	0.998
19:57572229:A:G	F559L	0.998
19:57572479:A:C	F475L	0.998
19:57572479:A:T	F475L	0.998
19:57572481:A:G	F475L	0.998
19:57572563:A:C	F447L	0.998
19:57572563:A:T	F447L	0.998
19:57572565:A:G	F447L	0.998
19:57572311:A:C	F531L	0.997
19:57572311:A:T	F531L	0.997
19:57572313:A:G	F531L	0.997
19:57572899:A:C	F335L	0.997
19:57572899:A:T	F335L	0.997
19:57572901:A:G	F335L	0.997
19:57572983:A:C	F307L	0.997
19:57572983:A:T	F307L	0.997
19:57572985:A:G	F307L	0.997
19:57572452:G:C	H484Q	0.996
19:57572452:G:T	H484Q	0.996
19:57572647:A:C	F419L	0.996
19:57572647:A:T	F419L	0.996
19:57572649:A:G	F419L	0.996
19:57572368:G:C	H512Q	0.995
19:57572368:G:T	H512Q	0.995
19:57572450:T:G	Q485P	0.995
19:57572454:G:T	H484N	0.995
19:57572815:A:C	F363L	0.995
19:57572815:A:T	F363L	0.995
19:57572817:A:G	F363L	0.995

dbSNP variants (sampled 300 via entrez): RS1000669958 (19:57579024 G>A,C), RS1000993940 (19:57573504 C>T), RS1001201647 (19:57576982 T>G), RS1001881866 (19:57576648 A>G), RS1002164665 (19:57571245 A>T), RS1002213781 (19:57571669 G>A), RS1002481433 (19:57578160 C>G,T), RS1002610026 (19:57578414 A>G), RS1003101315 (19:57575454 A>C), RS1003342619 (19:57579328 T>C), RS1003724577 (19:57575019 G>A,T), RS1003988817 (19:57578527 C>T), RS1004540963 (19:57574213 C>G), RS1004932165 (19:57574632 TAAGA>T), RS1004997891 (19:57579615 C>T)

Disease associations

OMIM: gene MIM:621253 | 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

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
ferrous chloride	decreases expression	1
avobenzone	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
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Coal	decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Smoke	increases abundance, decreases expression	1
Tobacco Smoke Pollution	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_XW44	HEK293 eGFP-ZNF416	Transformed cell line	Female

Clinical trials (associated diseases)

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