ZNF99

Summary

ZNF99 (zinc finger protein 99, HGNC:13175) is a protein-coding gene on chromosome 19p12, encoding Zinc finger protein 99 (A8MXY4). May be involved in transcriptional regulation.

Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 7652 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 179 total
• MANE Select transcript: NM_001080409

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13175
Approved symbol	ZNF99
Name	zinc finger protein 99
Location	19p12
Locus type	gene with protein product
Status	Approved
Aliases	MGC24986
Ensembl gene	ENSG00000213973
Ensembl biotype	protein_coding
OMIM	603981
Entrez	7652

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000596209

RefSeq mRNA: 1 — MANE Select: NM_001080409 NM_001080409

CCDS: CCDS59369

Canonical transcript exons

ENST00000596209 — 4 exons

Exon	Start	End
ENSE00002263497	22769198	22769324
ENSE00002281070	22768305	22768400
ENSE00002992853	22752183	22759682
ENSE00003212809	22784014	22784151

Expression profiles

Bgee: expression breadth broad, 20 present calls, max score 82.87.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2868 / max 51.4610, expressed in 93 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180258	0.1688	69
180257	0.1180	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.64	gold quality
ventricular zone	UBERON:0003053	59.39	gold quality
cortical plate	UBERON:0005343	58.39	silver quality
ganglionic eminence	UBERON:0004023	56.22	gold quality
lower lobe of lung	UBERON:0008949	51.37	silver quality
testis	UBERON:0000473	51.31	gold quality
buccal mucosa cell	CL:0002336	51.18	gold quality
right testis	UBERON:0004534	50.10	gold quality
left testis	UBERON:0004533	48.25	gold quality
bone marrow cell	CL:0002092	47.89	gold quality
smooth muscle tissue	UBERON:0001135	46.34	gold quality
sural nerve	UBERON:0015488	45.29	gold quality
endometrium	UBERON:0001295	44.35	silver quality
prefrontal cortex	UBERON:0000451	43.43	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
oviduct epithelium	UBERON:0004804	43.35	gold quality
bone marrow	UBERON:0002371	43.08	gold quality
kidney	UBERON:0002113	42.58	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
skin of hip	UBERON:0001554	42.54	silver quality
cortex of kidney	UBERON:0001225	42.39	gold quality
upper leg skin	UBERON:0004262	42.39	silver quality
muscle tissue	UBERON:0002385	42.27	gold quality
lymph node	UBERON:0000029	42.22	gold quality
duodenum	UBERON:0002114	42.16	gold quality
tonsil	UBERON:0002372	41.71	gold quality
adult mammalian kidney	UBERON:0000082	41.62	silver quality
skeletal muscle tissue	UBERON:0001134	41.54	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.72
E-MTAB-6142	no	25.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

217 targeting ZNF99, 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-3064-3P	100.00	70.09	1254
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AT-5P	99.96	70.83	2666
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

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf646	ENSDARG00000061424
danio_rerio	si:dkey-154p10.3	ENSDARG00000068366
danio_rerio	si:dkey-89b17.4	ENSDARG00000075545
danio_rerio	zgc:66472	ENSDARG00000075916
danio_rerio	si:ch211-148l7.4	ENSDARG00000094469
danio_rerio	znf576.1	ENSDARG00000097819
drosophila_melanogaster	Sry-delta	FBGN0003512
drosophila_melanogaster	az2	FBGN0025185
drosophila_melanogaster	hang	FBGN0026575
drosophila_melanogaster	CG3032	FBGN0029928
drosophila_melanogaster	CG2129	FBGN0030008
drosophila_melanogaster	CG11695	FBGN0030316
drosophila_melanogaster	CG8944	FBGN0030680
drosophila_melanogaster	CG7101	FBGN0030963
drosophila_melanogaster	CG1602	FBGN0033186
drosophila_melanogaster	CG18011	FBGN0033491
drosophila_melanogaster	CG12942	FBGN0033569
drosophila_melanogaster	CG8089	FBGN0033993
drosophila_melanogaster	indra	FBGN0035213
drosophila_melanogaster	CG10654	FBGN0036294
drosophila_melanogaster	CG6791	FBGN0037918
drosophila_melanogaster	CG17803	FBGN0038547
drosophila_melanogaster	CG12219	FBGN0043796
drosophila_melanogaster	CG30020	FBGN0050020
drosophila_melanogaster	pzg	FBGN0259785
drosophila_melanogaster	mld	FBGN0263490
drosophila_melanogaster	zf30C	FBGN0270924
caenorhabditis_elegans	ztf-15	WBGENE00011066
caenorhabditis_elegans		WBGENE00013734
caenorhabditis_elegans		WBGENE00015649

Paralogs (36): ZNF302 (ENSG00000089335), ZNF184 (ENSG00000096654), CTCF (ENSG00000102974), ZNF574 (ENSG00000105732), ZBTB24 (ENSG00000112365), ZNF142 (ENSG00000115568), CTCFL (ENSG00000124092), ZNF473 (ENSG00000142528), ZNF827 (ENSG00000151612), ZNF689 (ENSG00000156853), ZNF208 (ENSG00000160321), ZNF91 (ENSG00000167232), ZNF526 (ENSG00000167625), ZNF764 (ENSG00000169951), ZNF747 (ENSG00000169955), ZNF282 (ENSG00000170265), ZNF160 (ENSG00000170949), ZNF497 (ENSG00000174586), ZBTB34 (ENSG00000177125), ZNF771 (ENSG00000179965), ZNF48 (ENSG00000180035), ZNF594 (ENSG00000180626), ZBTB37 (ENSG00000185278), ZFP92 (ENSG00000189420), ZNF107 (ENSG00000196247), ZNF729 (ENSG00000196350), ZNF569 (ENSG00000196437), ZNF420 (ENSG00000197050), ZNF785 (ENSG00000197162), ZNF665 (ENSG00000197497), ZNF181 (ENSG00000197841), ZNF347 (ENSG00000197937), ZNF84 (ENSG00000198040), ZBTB48 (ENSG00000204859), ZNF845 (ENSG00000213799), ZNF688 (ENSG00000229809)

Protein

Protein identifiers

Zinc finger protein 99 — A8MXY4 (reviewed: A8MXY4)

All UniProt accessions (1): A8MXY4

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_001073878* (*=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 (28 total): zinc finger region 24, sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MXY4-F1	72.18	0.01

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 85 (showing top): chr19p12, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOMF_DNA_BINDING_TRANSCRIPTION_REPRESSOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, HMGA1_TARGET_GENES, MIR335_3P, MIR548E_5P, MIR548N, MIR23A_3P_MIR23B_3P, MIR23C, MIR6809_3P, MIR4753_3P, MIR561_3P

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (4): DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA binding (GO:0003677), zinc ion binding (GO:0008270), 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
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	1
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of transcription by RNA polymerase II	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
nucleic acid binding	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF99	OR4K15	Q8NH41	447
ZNF99	OR10S1	Q8NGN2	446
ZNF99	OR5W2	Q8NH69	430
ZNF99	OR5D13	Q8NGL4	417
ZNF99	OR5AR1	Q8NGP9	411
ZNF99	OR5D18	Q8NGL1	398
ZNF99	OR5P2	Q8WZ92	394
ZNF99	OR8K3	Q8NH51	380
ZNF99	DEFB115	Q30KQ5	371
ZNF99	ZNF280A	P59817	352
ZNF99	TMEM121	Q9BTD3	349
ZNF99	FAM133B	Q5BKY9	348
ZNF99	WDR44	Q5JSH3	332
ZNF99	TOGARAM2	Q6ZUX3	323
ZNF99	FSD1L	Q9BXM9	320

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ECE1	ZNF99	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (6): ZNF99 (Affinity Capture-MS), ZNF99 (PCA), ZNF99 (Negative Genetic), ZNF99 (Affinity Capture-MS), HSPA9 (Cross-Linking-MS (XL-MS)), ZNF99 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2VDQ7, A6NK75, A6NN14, A6NNF4, A8MQ14, A8MTY0, A8MXY4, B7Z6K7, E9QAG8, O43345, O75290, O75373, O75437, P0CJ79, P10751, P17017, P17019, P17035, P17038, P18749, P35789, P51522, Q03923, Q03938, Q05481, Q14585, Q3SYV7, Q4V348, Q5R5U3, Q5R8X1, Q5R9F0, Q5SXM1, Q6P5C7, Q6ZN08, Q6ZN57, Q6ZR52, Q86V71, Q86XN6, Q8IYB9, Q8N7Q3

Diamond homologs: A0A1W2PQL4, A6NK75, A6NN14, A6NNF4, A6NP11, A8MQ14, A8MTY0, A8MUV8, A8MXY4, B4DX44, B4DXR9, E9PYI1, O14628, O43345, O75290, O75346, O75373, O75437, O95780, P0CB33, P0DKX0, P0DPD5, P16373, P17019, P17038, P21506, P35789, P52736, P52738, P52744, Q03923, Q03924, Q03936, Q03938, Q05481, Q14586, Q14593, Q14929, Q15928, Q3KNS6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	152
Likely benign	20
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

327 predictions. Top by Δscore:

Variant	Effect	Δscore
19:22769237:T:A	donor_gain	1.0000
19:22769191:T:TA	donor_gain	0.9900
19:22769192:CCTCA:C	donor_loss	0.9900
19:22769193:CTCAC:C	donor_loss	0.9900
19:22769194:TCAC:T	donor_loss	0.9900
19:22769195:C:CC	donor_loss	0.9900
19:22769196:A:AC	donor_gain	0.9900
19:22769196:A:AG	donor_loss	0.9900
19:22769196:AC:A	donor_gain	0.9900
19:22769197:C:CC	donor_gain	0.9900
19:22769197:C:CT	donor_loss	0.9900
19:22769197:CC:C	donor_gain	0.9900
19:22759683:C:CC	acceptor_gain	0.9800
19:22759680:TAA:T	acceptor_gain	0.9700
19:22769180:A:AC	donor_gain	0.9700
19:22769322:TCC:T	acceptor_gain	0.9700
19:22769323:CCC:C	acceptor_gain	0.9700
19:22769181:A:C	donor_gain	0.9600
19:22769325:C:CC	acceptor_gain	0.9600
19:22768203:T:TA	donor_gain	0.9500
19:22769321:ATCCC:A	acceptor_loss	0.9500
19:22769322:TCCCT:T	acceptor_loss	0.9500
19:22769323:CC:C	acceptor_gain	0.9500
19:22769324:CC:C	acceptor_gain	0.9500
19:22769324:CCT:C	acceptor_loss	0.9500
19:22769325:CTGAA:C	acceptor_loss	0.9500
19:22769326:T:C	acceptor_loss	0.9500
19:22767927:A:C	acceptor_gain	0.9400
19:22769320:GATCC:G	acceptor_gain	0.9300
19:22768190:C:A	donor_gain	0.9200

AlphaMissense

5807 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:22757767:A:C	F714L	0.984
19:22757767:A:T	F714L	0.984
19:22757769:A:G	F714L	0.984
19:22757683:A:C	F742L	0.982
19:22757683:A:T	F742L	0.982
19:22757685:A:G	F742L	0.982
19:22758019:A:C	F630L	0.979
19:22758019:A:T	F630L	0.979
19:22758021:A:G	F630L	0.979
19:22758271:A:C	F546L	0.979
19:22758271:A:T	F546L	0.979
19:22758273:A:G	F546L	0.979
19:22758187:A:C	F574L	0.977
19:22758187:A:T	F574L	0.977
19:22758189:A:G	F574L	0.977
19:22757515:A:C	F798L	0.973
19:22757515:A:T	F798L	0.973
19:22757517:A:G	F798L	0.973
19:22758523:A:C	F462L	0.972
19:22758523:A:T	F462L	0.972
19:22758525:A:G	F462L	0.972
19:22758103:A:C	F602L	0.971
19:22758103:A:T	F602L	0.971
19:22758105:A:G	F602L	0.971
19:22758170:A:G	L580P	0.971
19:22757599:A:C	F770L	0.966
19:22757599:A:T	F770L	0.966
19:22757601:A:G	F770L	0.966
19:22757935:A:C	F658L	0.966
19:22757935:A:T	F658L	0.966

dbSNP variants (sampled 300 via entrez): RS1000179427 (19:22768967 T>C), RS1000201581 (19:22754905 A>G), RS1000286838 (19:22774888 A>C), RS1000537393 (19:22770644 C>G,T), RS1000630032 (19:22761694 C>T), RS1000706867 (19:22773776 A>G), RS1000728636 (19:22767278 C>A), RS1000811849 (19:22775212 G>C,T), RS1000844361 (19:22768674 A>G), RS1000903614 (19:22779600 A>C), RS1000986858 (19:22771067 T>A,C,G), RS1001032144 (19:22784602 AAAG>A), RS1001396628 (19:22783886 C>A,G,T), RS1001774312 (19:22755175 G>A,C), RS1001939772 (19:22755337 C>A,T)

Disease associations

OMIM: gene MIM:603981 | 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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Copper	affects cotreatment, decreases expression	1
Endosulfan	decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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