ZNF556

Summary

ZNF556 (zinc finger protein 556, HGNC:25669) is a protein-coding gene on chromosome 19p13.3, encoding Zinc finger protein 556 (Q9HAH1). 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 80032 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 92 total
• MANE Select transcript: NM_024967

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25669
Approved symbol	ZNF556
Name	zinc finger protein 556
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11637
Ensembl gene	ENSG00000172000
Ensembl biotype	protein_coding
Entrez	80032

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000307635, ENST00000586426, ENST00000586470

RefSeq mRNA: 2 — MANE Select: NM_024967 NM_001300843, NM_024967

CCDS: CCDS12097, CCDS74254

Canonical transcript exons

ENST00000307635 — 4 exons

Exon	Start	End
ENSE00001149847	2867335	2867424
ENSE00001235103	2877273	2883445
ENSE00001594294	2873496	2873622
ENSE00003521803	2876093	2876276

Expression profiles

Bgee: expression breadth broad, 99 present calls, max score 86.92.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8101 / max 56.2048, expressed in 210 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173131	0.6517	178
173130	0.1585	77

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	86.92	gold quality
oocyte	CL:0000023	83.73	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	80.74	gold quality
biceps brachii	UBERON:0001507	80.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.86	silver quality
diaphragm	UBERON:0001103	73.75	gold quality
amniotic fluid	UBERON:0000173	73.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.92	gold quality
epithelium of esophagus	UBERON:0001976	69.68	silver quality
esophagus squamous epithelium	UBERON:0006920	69.44	silver quality
skeletal muscle tissue	UBERON:0001134	65.92	gold quality
triceps brachii	UBERON:0001509	65.82	gold quality
gluteal muscle	UBERON:0002000	65.71	gold quality
squamous epithelium	UBERON:0006914	65.51	silver quality
hindlimb stylopod muscle	UBERON:0004252	64.10	gold quality
cervix squamous epithelium	UBERON:0006922	64.07	gold quality
body of tongue	UBERON:0011876	63.27	silver quality
cerebellar vermis	UBERON:0004720	62.78	silver quality
endometrium	UBERON:0001295	62.68	gold quality
muscle tissue	UBERON:0002385	62.64	gold quality
cerebellum	UBERON:0002037	61.74	gold quality
stromal cell of endometrium	CL:0002255	61.69	gold quality
left ovary	UBERON:0002119	61.61	gold quality
sperm	CL:0000019	61.42	silver quality
muscle organ	UBERON:0001630	61.03	gold quality
cerebellar cortex	UBERON:0002129	61.03	gold quality
cerebellar hemisphere	UBERON:0002245	60.82	gold quality
male germ cell	CL:0000015	60.68	silver quality
parotid gland	UBERON:0001831	60.58	gold quality
ovary	UBERON:0000992	60.28	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	709.45
E-ANND-3	yes	5.81
E-GEOD-81608	no	33.23
E-GEOD-124858	no	7.21
E-MTAB-5061	no	1.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting ZNF556, 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-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-370-3P	97.09	64.92	1221

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), ZNF554 (ENSG00000172006), ZNF596 (ENSG00000172748), ZNF80 (ENSG00000174255), ZNF266 (ENSG00000174652), ZNF25 (ENSG00000175395), ZNF77 (ENSG00000175691), ZNF169 (ENSG00000175787), ZNF404 (ENSG00000176222), ZNF491 (ENSG00000177599), 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 556 — Q9HAH1 (reviewed: Q9HAH1)

All UniProt accessions (3): Q9HAH1, A0A0C4DGQ3, K7EKA5

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 (2): NP_001287772, NP_079243* (*=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
IPR050758	Znf_C2H2-type	Family

Pfam: PF00096, PF01352, PF13894

UniProt features (21 total): zinc finger region 9, sequence variant 4, region of interest 3, compositionally biased region 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAH1-F1	65.43	0.06

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 28 (showing top): HATADA_METHYLATED_IN_LUNG_CANCER_DN, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, chr19p13, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, PTEN_DN.V1_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ASH1L_TARGET_GENES, CEBPZ_TARGET_GENES, CIITA_TARGET_GENES, NFKBIA_TARGET_GENES, ZNF184_TARGET_GENES, HELLER_HDAC_TARGETS_UP, AIZARANI_LIVER_C30_HEPATOCYTES_4, DESCARTES_MAIN_FETAL_SKELETAL_MUSCLE_CELLS, GSE18791_UNSTIM_VS_NEWCATSLE_VIRUS_DC_2H_UP

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 (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
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

Protein interactions and networks

STRING

344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF556	ZNF474	Q6S9Z5	447
ZNF556	IZUMO2	Q6UXV1	446
ZNF556	REP15	Q6BDI9	431
ZNF556	SUSD5	O60279	370
ZNF556	KLHDC10	Q6PID8	368
ZNF556	ACP6	Q9NPH0	320
ZNF556	TSEN2	Q8NCE0	313
ZNF556	MIOX	Q9UGB7	303
ZNF556	RSPO4	Q2I0M5	282
ZNF556	CILP2	Q8IUL8	270
ZNF556	SLCO4C1	Q6ZQN7	269
ZNF556	TRIM28	Q13263	253
ZNF556	CYP4V2	Q6ZWL3	246
ZNF556	SETDB1	Q15047	240
ZNF556	GMNN	O75496	225

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ZNF556	LRP4	psi-mi:“MI:0914”(association)	0.530
ZBTB3	ZNF556	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (21): TRMT12 (Affinity Capture-MS), ANKS3 (Affinity Capture-MS), UBE2O (Affinity Capture-MS), TRIM39 (Affinity Capture-MS), LRP4 (Affinity Capture-MS), MRPS24 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), MTHFR (Affinity Capture-MS), NEK7 (Affinity Capture-MS), ZNF556 (Two-hybrid), MRPS24 (Affinity Capture-MS), MRPS5 (Affinity Capture-MS), LRP4 (Affinity Capture-MS), ANKS3 (Affinity Capture-MS), NEDD8-MDP1 (Affinity Capture-MS)

ESM2 similar proteins: A0JPL0, A2A761, A3KN36, A7MBI1, A8MT65, B2RXC5, G3X9G7, P08042, P17023, P18728, P52738, Q02525, Q0D2J5, Q0VCB0, Q12901, Q2M3W8, Q2M3X9, Q49AA0, Q4R6J4, Q4V8A8, Q5FWF6, Q5JNZ3, Q5R7I8, Q5RB33, Q5REF1, Q5T5D7, Q61967, Q62396, Q6ZN11, Q6ZNG0, Q86XU0, Q8BGV5, Q8IZ26, Q8N782, Q8N859, Q8N9Z0, Q8NE65, Q8R2V3, Q8TF39, Q96BR6

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

549 predictions. Top by Δscore:

Variant	Effect	Δscore
19:2867423:TGGTG:T	donor_loss	1.0000
19:2867424:GGT:G	donor_loss	1.0000
19:2867425:GT:G	donor_loss	1.0000
19:2867426:T:A	donor_loss	1.0000
19:2873488:T:TA	acceptor_gain	1.0000
19:2873494:A:AG	acceptor_gain	1.0000
19:2873494:AG:A	acceptor_gain	1.0000
19:2873495:G:GG	acceptor_gain	1.0000
19:2873495:GG:G	acceptor_gain	1.0000
19:2873495:GGA:G	acceptor_gain	1.0000
19:2873495:GGAC:G	acceptor_gain	1.0000
19:2873495:GGACA:G	acceptor_gain	1.0000
19:2873619:GTAG:G	donor_gain	1.0000
19:2873621:AGG:A	donor_loss	1.0000
19:2873623:G:GG	donor_gain	1.0000
19:2873624:T:G	donor_loss	1.0000
19:2867410:A:T	donor_gain	0.9900
19:2867421:CATG:C	donor_gain	0.9900
19:2867423:TG:T	donor_gain	0.9900
19:2867424:GG:G	donor_gain	0.9900
19:2867425:G:GG	donor_gain	0.9900
19:2873491:TTTAG:T	acceptor_gain	0.9900
19:2873492:TTA:T	acceptor_gain	0.9900
19:2873493:TA:T	acceptor_gain	0.9900
19:2873494:A:AC	acceptor_gain	0.9900
19:2873495:G:T	acceptor_gain	0.9900
19:2873620:TAG:T	donor_gain	0.9900
19:2875001:G:GT	donor_gain	0.9900
19:2867420:ACATG:A	donor_gain	0.9800
19:2867422:ATG:A	donor_gain	0.9800

AlphaMissense

3011 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:2877676:T:C	F240L	0.998
19:2877678:C:A	F240L	0.998
19:2877678:C:G	F240L	0.998
19:2877928:T:C	F324L	0.997
19:2877930:C:A	F324L	0.997
19:2877930:C:G	F324L	0.997
19:2877592:T:C	F212L	0.996
19:2877594:T:A	F212L	0.996
19:2877594:T:G	F212L	0.996
19:2877760:T:C	F268L	0.996
19:2877762:C:A	F268L	0.996
19:2877762:C:G	F268L	0.996
19:2877873:C:A	H305Q	0.993
19:2877873:C:G	H305Q	0.993
19:2877621:T:A	H221Q	0.992
19:2877621:T:G	H221Q	0.992
19:2877705:T:A	H249Q	0.992
19:2877705:T:G	H249Q	0.992
19:2877508:T:C	F184L	0.991
19:2877510:C:A	F184L	0.991
19:2877510:C:G	F184L	0.991
19:2877863:T:C	F302S	0.990
19:2877677:T:C	F240S	0.989
19:2877869:G:C	R304P	0.988
19:2877633:C:A	H225Q	0.987
19:2877633:C:G	H225Q	0.987
19:2873530:T:C	F13S	0.985
19:2877789:T:A	H277Q	0.985
19:2877789:T:G	H277Q	0.985
19:2877695:T:C	F246S	0.983

dbSNP variants (sampled 300 via entrez): RS1000000942 (19:2879028 A>G), RS1000295290 (19:2866388 G>A,C), RS1000433434 (19:2873749 T>C), RS1000786223 (19:2870375 C>A,G), RS1000925244 (19:2870186 C>T), RS1001007848 (19:2879857 C>T), RS1001147901 (19:2883441 A>G), RS1001236152 (19:2873845 T>C), RS1001253990 (19:2883001 C>A,T), RS1001286026 (19:2883119 C>T), RS1001321787 (19:2879001 A>C,T), RS1001349642 (19:2869235 C>T), RS1001412087 (19:2868944 C>G), RS1001605299 (19:2874013 T>C), RS1001927338 (19:2871267 G>A)

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

3 associations (top):

Study	Trait	p-value
GCST003070_4	Cerebrospinal T-tau levels	5.000000e-07
GCST003079_6	Cerebrospinal fluid t-tau:AB1-42 ratio	3.000000e-06
GCST003518_101	Daytime sleep phenotypes	8.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004760	t-tau measurement
EFO:0007708	t-tau:beta-amyloid 1-42 ratio measurement
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sotorasib	affects cotreatment, decreases expression	1
potassium chromate(VI)	increases expression	1
gallium arsenide	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
trametinib	decreases expression, affects cotreatment	1
NVP-BKM120	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Hydralazine	affects cotreatment, increases expression	1
Silicon Dioxide	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Vanadates	decreases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	increases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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