ZNF518A

Summary

ZNF518A (zinc finger protein 518A, HGNC:29009) is a protein-coding gene on chromosome 10q24.1, encoding Zinc finger protein 518A (Q6AHZ1). Through its association with the EHMT1-EHMT2/G9A and PRC2/EED-EZH2 histone methyltransferase complexes may function in gene silencing, regulating repressive post-translational methylation of histone tails at promoters of target genes.

The protein encoded by this gene is a member of the krueppel C2H2-type zinc finger protein family. The encoded protein contains five zinc fingers and is likely a nuclear transcriptional regulator. Numerous transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 9849 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 202 total
• MANE Select transcript: NM_001330736

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29009
Approved symbol	ZNF518A
Name	zinc finger protein 518A
Location	10q24.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0335
Ensembl gene	ENSG00000177853
Ensembl biotype	protein_coding
OMIM	617733
Entrez	9849

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 40 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000316045, ENST00000442635, ENST00000484770, ENST00000488700, ENST00000534948, ENST00000539666, ENST00000563195, ENST00000614149, ENST00000624776, ENST00000863556, ENST00000863558, ENST00000863559, ENST00000863560, ENST00000863561, ENST00000863562, ENST00000937970, ENST00000937971, ENST00000937972, ENST00000937973, ENST00000937974, ENST00000937975, ENST00000937976, ENST00000937977, ENST00000937978, ENST00000937979, ENST00000937980, ENST00000937981, ENST00000937982, ENST00000937983, ENST00000937984, ENST00000937985, ENST00000937986, ENST00000937987, ENST00000937988, ENST00000937989, ENST00000937990, ENST00000937991, ENST00000937992, ENST00000937993, ENST00000937994, ENST00000937995, ENST00000937996, ENST00000937997, ENST00000937998, ENST00000948079, ENST00000948080

RefSeq mRNA: 11 — MANE Select: NM_001330736 NM_001278524, NM_001278525, NM_001278526, NM_001330732, NM_001330733, NM_001330734, NM_001330735, NM_001330736, NM_001330737, NM_001330738, NM_014803

CCDS: CCDS73170

Canonical transcript exons

ENST00000316045 — 6 exons

Exon	Start	End
ENSE00001235653	96156197	96163759
ENSE00001532941	96155924	96156047
ENSE00001532944	96133583	96133648
ENSE00001532948	96132586	96132670
ENSE00003923375	96155326	96155376
ENSE00003926755	96130297	96130752

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 98.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5108 / max 253.7529, expressed in 1691 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106375	4.5194	1448
106376	2.3594	1080
106373	1.8124	784
106378	0.5302	267
106374	0.2894	119

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	98.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.45	gold quality
adrenal tissue	UBERON:0018303	94.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.13	gold quality
tendon of biceps brachii	UBERON:0008188	90.03	silver quality
calcaneal tendon	UBERON:0003701	90.01	gold quality
corpus epididymis	UBERON:0004359	89.44	gold quality
corpus callosum	UBERON:0002336	89.04	gold quality
tendon	UBERON:0000043	88.78	gold quality
caput epididymis	UBERON:0004358	88.18	gold quality
right uterine tube	UBERON:0001302	88.01	gold quality
trabecular bone tissue	UBERON:0002483	87.48	gold quality
jejunal mucosa	UBERON:0000399	86.90	gold quality
colonic epithelium	UBERON:0000397	86.49	gold quality
visceral pleura	UBERON:0002401	86.24	gold quality
rectum	UBERON:0001052	86.10	gold quality
cauda epididymis	UBERON:0004360	86.09	gold quality
endometrium	UBERON:0001295	86.08	gold quality
monocyte	CL:0000576	85.27	gold quality
testis	UBERON:0000473	85.24	gold quality
tibia	UBERON:0000979	85.07	gold quality
mononuclear cell	CL:0000842	84.94	gold quality
body of pancreas	UBERON:0001150	84.85	gold quality
germinal epithelium of ovary	UBERON:0001304	84.74	gold quality
right lobe of thyroid gland	UBERON:0001119	84.63	gold quality
leukocyte	CL:0000738	84.58	gold quality
thyroid gland	UBERON:0002046	84.58	gold quality
parietal pleura	UBERON:0002400	84.32	gold quality
pleura	UBERON:0000977	84.27	gold quality
right testis	UBERON:0004534	84.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

172 targeting ZNF518A, 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-3613-3P	100.00	76.36	7965
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
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-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-190A-3P	100.00	80.35	5520
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6778-3P	99.96	67.29	2693

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp518a	ENSMUSG00000049164
rattus_norvegicus	Zfp518a	ENSRNOG00000036592
drosophila_melanogaster	hb	FBGN0001180
drosophila_melanogaster	CG12391	FBGN0033581
caenorhabditis_elegans		WBGENE00001824
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), ZNF641 (ENSG00000167528), ZNF444 (ENSG00000167685), SCAND1 (ENSG00000171222), ZNF274 (ENSG00000171606), ZNF131 (ENSG00000172262), OVOL1 (ENSG00000172818), ZNF518B (ENSG00000178163), PLAG1 (ENSG00000181690), ZSCAN5B (ENSG00000197213), ZNF770 (ENSG00000198146), PEG3 (ENSG00000198300), ZSCAN5C (ENSG00000204532)

Protein

Protein identifiers

Zinc finger protein 518A — Q6AHZ1 (reviewed: Q6AHZ1)

All UniProt accessions (1): Q6AHZ1

UniProt curated annotations — full annotation on UniProt →

Function. Through its association with the EHMT1-EHMT2/G9A and PRC2/EED-EZH2 histone methyltransferase complexes may function in gene silencing, regulating repressive post-translational methylation of histone tails at promoters of target genes.

Subcellular location. Nucleus.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q6AHZ1-1	1	yes
Q6AHZ1-2	2

RefSeq proteins (11): NP_001265453, NP_001265454, NP_001265455, NP_001317661, NP_001317662, NP_001317663, NP_001317664, NP_001317665, NP_001317666, NP_001317667, NP_055618 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050888	ZnF_C2H2-type_TF	Family

UniProt features (36 total): cross-link 20, zinc finger region 5, sequence variant 2, sequence conflict 2, region of interest 2, compositionally biased region 2, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6AHZ1-F1	40.97	0.01

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 (21): 655, 24, 357, 392, 425, 433, 524, 596, 713, 798, 889, 902, 928, 994, 1015, 1048, 1060, 1083, 1121, 1185 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 128 (showing top): AAGCCAT_MIR135A_MIR135B, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, CACCAGC_MIR138, CTATGCA_MIR153, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, FISCHER_G2_M_CELL_CYCLE, KIM_GERMINAL_CENTER_T_HELPER_UP, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, FISCHER_DREAM_TARGETS, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, CUI_TCF21_TARGETS_2_DN, TTTGCAC_MIR19A_MIR19B, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, LAIHO_COLORECTAL_CANCER_SERRATED_DN

GO Biological Process (2): chromatin organization (GO:0006325), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (4): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), zinc ion binding (GO:0008270), 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
cellular component organization	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	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
nucleic acid binding	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

792 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF518A	ZCCHC2	Q9C0B9	559
ZNF518A	BCLAF3	A2AJT9	507
ZNF518A	TMEM150B	A6NC51	467
ZNF518A	U2SURP	O15042	464
ZNF518A	ZNF782	Q6ZMW2	448
ZNF518A	THOC1	Q96FV9	423
ZNF518A	EHMT2	Q96KQ7	407
ZNF518A	CDCP2	Q5VXM1	400
ZNF518A	MAGEB3	O15480	390
ZNF518A	H1-10	Q92522	384
ZNF518A	EPS8L1	Q8TE68	372
ZNF518A	ZNF20	P17024	371
ZNF518A	HMCES	Q96FZ2	359
ZNF518A	ZNF337	Q9Y3M9	348
ZNF518A	SREK1	Q8WXA9	343

IntAct

65 interactions, top by confidence:

A	B	Type	Score
XPA	ERCC1	psi-mi:“MI:0914”(association)	0.930
APBA2	HERC2	psi-mi:“MI:0914”(association)	0.530
EIPR1	LDHC	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
CBX1	ZNF292	psi-mi:“MI:0914”(association)	0.530
ZNF518A	USP11	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF518A	RRBP1	psi-mi:“MI:0915”(physical association)	0.400
ZNF518A	ATF7IP	psi-mi:“MI:0915”(physical association)	0.370
Rhoa	CLK2	psi-mi:“MI:0914”(association)	0.350
HDAC6	GLOD5	psi-mi:“MI:0914”(association)	0.350
HIF1A	PIAS1	psi-mi:“MI:0914”(association)	0.350
GSTP1	GABPB1	psi-mi:“MI:0914”(association)	0.350
CBR1	DENND3	psi-mi:“MI:0914”(association)	0.350
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.350
PCDHA12	KLRG2	psi-mi:“MI:0914”(association)	0.350
PCDHGB4	FAM171A2	psi-mi:“MI:0914”(association)	0.350
PCDH20		psi-mi:“MI:0914”(association)	0.350
PCDHGA5	MAP2K7	psi-mi:“MI:0914”(association)	0.350
BBS7	PER1	psi-mi:“MI:0914”(association)	0.350
CBX5	ZNF568	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
LURAP1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
FBLN5	ZNF320	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
BBS7	TARS3	psi-mi:“MI:0914”(association)	0.350
CDH23	GTPBP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (63): ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS), ZNF518A (Affinity Capture-MS)

ESM2 similar proteins: A0JNH1, A2RRX6, A6QNQ6, B2RRE4, B2RRF6, D3Z987, O75362, P56716, Q01954, Q0VBV7, Q28BT7, Q2M2Z5, Q32N19, Q3TNU4, Q3U0P1, Q3URK3, Q3UXL4, Q3V089, Q3V0A6, Q499M7, Q499R0, Q5DTT3, Q5HZI1, Q5R9I1, Q5RC05, Q5T3J3, Q5VWN6, Q6AHZ1, Q6NU19, Q6PG16, Q7TSH4, Q7Z4V0, Q86XD8, Q86YC2, Q8CDD9, Q8IXJ9, Q8MJ03, Q8MJ04, Q8MJ05, Q8NAP3

Diamond homologs: B2RRE4, B2RRF6, Q2I689, Q499R0, Q6AHZ1, Q9C0D4, Q9UM63, B0XS89, B1WBU4, J9VE33, P54785, P80944, Q0VCJ6, Q29419, Q58NQ5, Q5SVQ8, Q5U2T6, Q65XX7, Q6DJT9, Q6P882, Q811F1, Q96BR9, Q9CWH1, Q9QYE0, Q9UPG8, A1L2U9, B1WAZ8, Q0IH98, Q01611, Q95LI3, A0A1V6NWD3, O77459, P28166, P39956, P60319, Q02027, Q03833, Q10938, Q14119, Q292R5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	173
Likely benign	21
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2731 predictions. Top by Δscore:

Variant	Effect	Δscore
10:96200155:CTTC:C	acceptor_gain	1.0000
10:96200157:TCCTG:T	acceptor_loss	1.0000
10:96200159:C:CA	acceptor_loss	1.0000
10:96200159:C:CC	acceptor_gain	1.0000
10:96200160:T:A	acceptor_loss	1.0000
10:96204526:TCTTA:T	donor_loss	1.0000
10:96204527:CTTAC:C	donor_loss	1.0000
10:96204528:TTACT:T	donor_loss	1.0000
10:96204529:TA:T	donor_loss	1.0000
10:96204530:A:AC	donor_gain	1.0000
10:96204530:ACT:A	donor_loss	1.0000
10:96204531:C:CT	donor_gain	1.0000
10:96204531:CT:C	donor_gain	1.0000
10:96204531:CTT:C	donor_gain	1.0000
10:96204533:T:TA	donor_gain	1.0000
10:96204617:C:CC	acceptor_gain	1.0000
10:96204624:A:T	acceptor_gain	1.0000
10:96130100:GCAA:G	donor_gain	0.9900
10:96133646:GCA:G	donor_gain	0.9900
10:96133649:G:GG	donor_gain	0.9900
10:96156012:A:G	donor_gain	0.9900
10:96192090:GTA:G	acceptor_gain	0.9900
10:96192091:TA:T	acceptor_gain	0.9900
10:96192093:C:CC	acceptor_gain	0.9900
10:96196907:CCTCT:C	donor_gain	0.9900
10:96197078:T:TC	acceptor_gain	0.9900
10:96200156:TTC:T	acceptor_gain	0.9900
10:96200157:TC:T	acceptor_gain	0.9900
10:96200158:CC:C	acceptor_gain	0.9900
10:96204530:ACTT:A	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000027537 (10:96181569 G>A,C), RS1000131386 (10:96170718 A>G), RS1000186040 (10:96142644 T>C), RS1000226127 (10:96133408 A>G), RS1000255807 (10:96133116 T>C), RS1000257984 (10:96177100 A>T), RS1000312530 (10:96184796 T>C,G), RS1000348200 (10:96164079 A>G), RS1000365107 (10:96184380 C>G,T), RS1000538935 (10:96146185 T>C), RS1000653444 (10:96145766 C>A), RS1000690368 (10:96152549 A>G), RS1000702250 (10:96199908 C>T), RS1000852563 (10:96139778 A>G,T), RS1000955213 (10:96165669 C>T)

Disease associations

OMIM: gene MIM:617733 | disease phenotypes: MIM:613502

GenCC curated gene-disease

Mondo (1): agammaglobulinemia 4, autosomal recessive (MONDO:0013289)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008839_193	Height	9.000000e-11
GCST90000047_208	Age at first sexual intercourse	6.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	3
potassium chromate(VI)	decreases expression, affects cotreatment	2
Vorinostat	decreases expression	2
Endosulfan	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	increases methylation, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
geldanamycin	increases expression	1
bufotalin	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	decreases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
ochratoxin A	decreases acetylation, decreases expression	1
nickel sulfate	decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
chromium hexavalent ion	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
dorsomorphin	affects cotreatment, decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
licochalcone B	decreases expression	1
bisphenol S	increases methylation	1
jinfukang	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases 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_XW56	HEK293 eGFP-ZNF518A	Transformed cell line	Female

Clinical trials (associated diseases)

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