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GGNBP2

gene
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Also known as ZFP403LZK1FLJ22561FLJ21230DIF-3DIF3

Summary

GGNBP2 (gametogenetin binding protein 2, HGNC:19357) is a protein-coding gene on chromosome 17q12, encoding Gametogenetin-binding protein 2 (Q9H3C7). May be involved in spermatogenesis. It is a selective cancer dependency (DepMap: 18.5% of cell lines).

Predicted to be involved in spermatogenesis. Predicted to act upstream of or within several processes, including labyrinthine layer blood vessel development; negative regulation of cell population proliferation; and negative regulation of peptidyl-tyrosine phosphorylation. Predicted to be located in cytoplasmic vesicle. Predicted to be active in cytoplasm and nucleus.

Source: NCBI Gene 79893 — RefSeq curated summary.

At a glance

  • GWAS associations: 6
  • Clinical variants (ClinVar): 99 total — 2 pathogenic
  • Cancer dependency (DepMap): dependent in 18.5% of screened cell lines
  • MANE Select transcript: NM_024835

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:19357
Approved symbolGGNBP2
Namegametogenetin binding protein 2
Location17q12
Locus typegene with protein product
StatusApproved
AliasesZFP403, LZK1, FLJ22561, FLJ21230, DIF-3, DIF3
Ensembl geneENSG00000278311
Ensembl biotypeprotein_coding
OMIM612275
Entrez79893

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 5 retained_intron

ENST00000611219, ENST00000612563, ENST00000613102, ENST00000615952, ENST00000616019, ENST00000617860, ENST00000618837, ENST00000619573, ENST00000620927, ENST00000870040, ENST00000870041, ENST00000870042, ENST00000870043, ENST00000870044, ENST00000870045, ENST00000870046, ENST00000870047, ENST00000934643, ENST00000934644, ENST00000970049, ENST00000970050, ENST00000970051, ENST00000970052, ENST00000970053

RefSeq mRNA: 1 — MANE Select: NM_024835 NM_024835

CCDS: CCDS11314

Canonical transcript exons

ENST00000613102 — 14 exons

ExonStartEnd
ENSE000037125473657924536579419
ENSE000037160453656766336567776
ENSE000037168183658134436581538
ENSE000037176973658699736587245
ENSE000037248063654561936545817
ENSE000037267303654491936545097
ENSE000037281523656077336560871
ENSE000037353163657798336578186
ENSE000037430063658920836589848
ENSE000037432973658530036585450
ENSE000037435463658605036586198
ENSE000037436503655708336557336
ENSE000037511533655482036554900
ENSE000037517213658584036585965

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.7885 / max 743.7405, expressed in 1824 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter IDTPM avgSamples expressed
16042725.84781817
16043014.05251793
1604281.1738613
1604290.7524396
1604350.6018184
1604360.3601140

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
left testisUBERON:000453397.33gold quality
right testisUBERON:000453497.28gold quality
testisUBERON:000047396.85gold quality
mucosa of stomachUBERON:000119996.83gold quality
endometriumUBERON:000129596.82gold quality
small intestine Peyer’s patchUBERON:000345496.64gold quality
lymph nodeUBERON:000002996.31gold quality
calcaneal tendonUBERON:000370196.24gold quality
monocyteCL:000057696.22gold quality
spleenUBERON:000210696.18gold quality
bone marrowUBERON:000237196.16gold quality
skin of abdomenUBERON:000141696.13gold quality
small intestineUBERON:000210896.12gold quality
leukocyteCL:000073896.10gold quality
left ovaryUBERON:000211996.10gold quality
right ovaryUBERON:000211896.05gold quality
olfactory segment of nasal mucosaUBERON:000538696.04gold quality
subcutaneous adipose tissueUBERON:000219096.02gold quality
right lungUBERON:000216795.94gold quality
ovaryUBERON:000099295.93gold quality
transverse colonUBERON:000115795.87gold quality
zone of skinUBERON:000001495.83gold quality
tibial arteryUBERON:000761095.80gold quality
popliteal arteryUBERON:000225095.79gold quality
body of pancreasUBERON:000115095.77gold quality
intestineUBERON:000016095.74gold quality
adipose tissueUBERON:000101395.68gold quality
muscle layer of sigmoid colonUBERON:003580595.68gold quality
left uterine tubeUBERON:000130395.67gold quality
tibial nerveUBERON:000132395.66gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-GEOD-100618no730.69
E-MTAB-7052no229.28
E-ANND-3no0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting GGNBP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4776-3P100.0068.731340
HSA-MIR-513A-5P100.0069.772465
HSA-MIR-574-5P100.0066.01989
HSA-MIR-150-5P99.9966.691976
HSA-MIR-428299.9975.366408
HSA-MIR-607799.9968.042299
HSA-MIR-50799.9770.111915
HSA-MIR-302C-5P99.9772.563642
HSA-MIR-55799.9670.011640
HSA-MIR-365899.9673.874379
HSA-MIR-548AA99.9670.643753
HSA-MIR-548AP-3P99.9670.643753
HSA-MIR-548T-3P99.9670.643753
HSA-MIR-551B-5P99.9671.283493
HSA-MIR-23A-3P99.9574.243163
HSA-MIR-23B-3P99.9574.243163
HSA-MIR-23C99.9573.923192
HSA-MIR-314399.9371.963104
HSA-MIR-450B-5P99.9271.483175
HSA-MIR-368699.9070.532432
HSA-LET-7A-2-3P99.8770.531921
HSA-LET-7G-3P99.8570.431929
HSA-MIR-3681-5P99.8266.88387
HSA-MIR-313399.8170.923506
HSA-MIR-323A-3P99.7970.301739
HSA-MIR-4713-5P99.7867.801794
HSA-MIR-465899.7764.94514
HSA-MIR-6790-5P99.7765.24505
HSA-MIR-3680-3P99.7572.513095
HSA-MIR-199A-3P99.7570.48929

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

  • LCRG1 is a novel gene localized to the tumor suppressor locus D17S800-D17S930 involved in laryngeal carcinoma. (PMID:15145523)
  • There is an essential role for ZNF403 in cell proliferation and G2/M cell-cycle transition. (PMID:22350815)
  • Results show that downregulation of RNASET2 and GGNBP2 in drug-resistant ovarian cancer tissues/cells contributes to the regulation of drug resistance in ovarian cancer. (PMID:24842157)
  • Results identified GGNBP2 as a novel tumor suppressor which is downregulated in human breast tumors and cell lines and suggest that GGNBP2 may function as a corepressor to inhibit ERa’s transcriptional activity and consequently inhibit tumorigenic potential of breast cancer cells. (PMID:27357812)
  • The effects of ZFP403 on cell proliferation and metastasis suggest that it may serve as a tumor suppressor in ovarian cancer. (PMID:28864131)
  • Our data demonstrate that GGNBP2 suppresses cancer aggressiveness by inhibition of IL-6/STAT3 activation in triple-negative breast cancer (PMID:30450530)
  • Effects of gametogenetin-binding protein 2 on proliferation, invasion and migration of prostate cancer PC-3 cells. (PMID:31797427)
  • Effects of zinc finger protein 403 on the proliferation, migration and invasion abilities of prostate cancer cells. (PMID:33125130)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_rerioggnbp2ENSDARG00000055086
mus_musculusGgnbp2ENSMUSG00000020530
rattus_norvegicusGgnbp2ENSRNOG00000027860
drosophila_melanogasterCG2182FBGN0037360

Protein

Protein identifiers

Gametogenetin-binding protein 2 — Q9H3C7 (reviewed: Q9H3C7)

Alternative names: Laryngeal carcinoma-related protein 1, Protein ZNF403

All UniProt accessions (4): Q9H3C7, A0A087X0E5, A0A087X1D7, A0A087X1N0

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in spermatogenesis.

Subunit / interactions. Interacts with GGN.

Subcellular location. Cytoplasmic vesicle.

Tissue specificity. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Expressed more abundantly in heart, pancreas and skeletal muscle.

Miscellaneous. Strongly down-regulated in 40% of primary laryngeal carcinoma and in 6 of 10 various cancer cell lines.

Isoforms (3)

UniProt IDNamesCanonical?
Q9H3C7-11yes
Q9H3C7-22
Q9H3C7-33

RefSeq proteins (1): NP_079111* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR026073GGNBP2Family

UniProt features (9 total): splice variant 4, helix 2, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
8BFJX-RAY DIFFRACTION2.23

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9H3C7-F169.800.39

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): 360

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (7): spermatogenesis (GO:0007283), negative regulation of cell population proliferation (GO:0008285), negative regulation of gene expression (GO:0010629), cell differentiation (GO:0030154), labyrinthine layer blood vessel development (GO:0060716), negative regulation of receptor signaling pathway via STAT (GO:1904893), labyrinthine layer development (GO:0060711)

GO Molecular Function (0):

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
developmental process involved in reproduction1
male gamete generation1
cell population proliferation1
regulation of cell population proliferation1
negative regulation of cellular process1
gene expression1
regulation of gene expression1
negative regulation of macromolecule biosynthetic process1
cellular developmental process1
embryonic organ development1
placenta blood vessel development1
labyrinthine layer development1
negative regulation of signal transduction1
cell surface receptor signaling pathway via STAT1
regulation of receptor signaling pathway via STAT1
embryonic placenta development1
anatomical structure development1
intracellular membrane-bounded organelle1
intracellular anatomical structure1
cellular anatomical structure1
cytoplasm1
intracellular vesicle1

Protein interactions and networks

STRING

2204 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
GGNBP2OAZ3Q9UMX2779
GGNBP2ZNHIT3Q15649662
GGNBP2GGNQ86UU5646
GGNBP2PIGWQ7Z7B1645
GGNBP2MYO19Q96H55644
GGNBP2MRM1Q6IN84643
GGNBP2SYNRGQ9UMZ2627
GGNBP2C17orf78Q8N4C9604
GGNBP2CRISP2P16562579
GGNBP2TADA2AO75478571
GGNBP2DHRS11Q6UWP2569
GGNBP2DDX52Q9Y2R4548
GGNBP2AATFQ9NY61547
GGNBP2IER3P46695542
GGNBP2SPATA4Q8NEY3465

IntAct

9 interactions, top by confidence:

ABTypeScore
CNOT11CNOT1psi-mi:“MI:0914”(association)0.770
ZNF331USP9Ypsi-mi:“MI:0914”(association)0.530
ESR1ESYT2psi-mi:“MI:0914”(association)0.350
CNOT11CNOT1psi-mi:“MI:0914”(association)0.350
PAK4ARHGEF11psi-mi:“MI:0914”(association)0.350
DTX3RAD50psi-mi:“MI:0914”(association)0.350

BioGRID (22): GGNBP2 (Affinity Capture-MS), GGNBP2 (Affinity Capture-MS), GGNBP2 (Affinity Capture-MS), GGNBP2 (Affinity Capture-MS), GGNBP2 (Proximity Label-MS), GGNBP2 (Affinity Capture-MS), GGNBP2 (Affinity Capture-MS), GGNBP2 (Affinity Capture-MS), GGNBP2 (Affinity Capture-MS), GGNBP2 (Affinity Capture-MS), GGNBP2 (Negative Genetic), GGNBP2 (Proximity Label-MS), GGNBP2 (Affinity Capture-MS), GGNBP2 (Affinity Capture-MS), GGNBP2 (Affinity Capture-MS)

ESM2 similar proteins: A1L3F5, A5WW08, A9ZLX4, F1R7R1, O17482, O35589, O54828, O75916, O94988, P12757, P49140, P49805, Q02225, Q13506, Q28C33, Q3B7M3, Q3UD82, Q4QQM5, Q5DTY9, Q5FWP4, Q5HYC2, Q5R431, Q5SV77, Q5XJS0, Q60665, Q61122, Q62722, Q63ZG9, Q68DU8, Q68FD7, Q6DFP9, Q6DH86, Q6GVH4, Q6GVH5, Q6NRH3, Q6P256, Q76CY8, Q7TP65, Q86XL3, Q8AVJ1

Diamond homologs: Q5SV77, Q63ZG9, Q6DFP9, Q6GVH4, Q6GVH5, Q9H3C7, Q9VNG1

SIGNOR signaling

1 interactions.

AEffectBMechanism
GGNBP2“down-regulates activity”ESR1binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic2
Likely pathogenic0
Uncertain significance63
Likely benign7
Benign4

Top pathogenic / likely-pathogenic (2)

Variant IDHGVSClassification
625612GRCh37/hg19 17q12(chr17:34848678-36194230)Pathogenic
980158GRCh37/hg19 17q12(chr17:34822465-36410559)x3Pathogenic

SpliceAI

2321 predictions. Top by Δscore:

VariantEffectΔscore
17:36545093:GAAGG:Gdonor_gain1.0000
17:36545096:GG:Gdonor_gain1.0000
17:36545097:GG:Gdonor_gain1.0000
17:36545817:GGTGA:Gdonor_loss1.0000
17:36545818:GTGAG:Gdonor_loss1.0000
17:36545819:T:Gdonor_loss1.0000
17:36554812:A:AGacceptor_gain1.0000
17:36554813:T:Gacceptor_gain1.0000
17:36554814:TTTAA:Tacceptor_loss1.0000
17:36554815:TTAA:Tacceptor_loss1.0000
17:36554816:TAAGA:Tacceptor_loss1.0000
17:36554817:A:AGacceptor_gain1.0000
17:36554817:AAGA:Aacceptor_loss1.0000
17:36554817:AAGAT:Aacceptor_gain1.0000
17:36554818:A:AGacceptor_gain1.0000
17:36554818:AGAT:Aacceptor_gain1.0000
17:36554819:G:GGacceptor_gain1.0000
17:36554819:G:GTacceptor_loss1.0000
17:36554819:GAT:Gacceptor_gain1.0000
17:36554819:GATG:Gacceptor_gain1.0000
17:36554896:TTCAG:Tdonor_loss1.0000
17:36554897:TCAG:Tdonor_loss1.0000
17:36554898:CAG:Cdonor_loss1.0000
17:36554899:AG:Adonor_loss1.0000
17:36554900:GGTA:Gdonor_loss1.0000
17:36554901:GT:Gdonor_loss1.0000
17:36554902:T:Adonor_loss1.0000
17:36557082:GCGAC:Gacceptor_gain1.0000
17:36557335:GG:Gdonor_gain1.0000
17:36557336:GG:Gdonor_gain1.0000

AlphaMissense

4656 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
17:36557173:T:AC89S1.000
17:36557173:T:CC89R1.000
17:36557174:G:AC89Y1.000
17:36557174:G:CC89S1.000
17:36557174:G:TC89F1.000
17:36557175:T:GC89W1.000
17:36557177:T:AV90D1.000
17:36557179:G:CG91R1.000
17:36557179:G:TG91C1.000
17:36557180:G:AG91D1.000
17:36557182:T:CC92R1.000
17:36557183:G:AC92Y1.000
17:36557185:C:AR93S1.000
17:36557186:G:CR93P1.000
17:36560813:A:GK157E1.000
17:36560815:G:CK157N1.000
17:36560815:G:TK157N1.000
17:36560826:G:CR161T1.000
17:36560827:A:CR161S1.000
17:36560827:A:TR161S1.000
17:36560828:T:AC162S1.000
17:36560828:T:CC162R1.000
17:36560829:G:AC162Y1.000
17:36560829:G:CC162S1.000
17:36560830:T:GC162W1.000
17:36560837:C:GH165D1.000
17:36560839:C:AH165Q1.000
17:36560839:C:GH165Q1.000
17:36560840:T:CS166P1.000
17:36567670:T:AW179R1.000

dbSNP variants (sampled 300 via entrez): RS1000267841 (17:36546905 G>A,T), RS1000292268 (17:36582438 G>A), RS1000515130 (17:36558615 T>G), RS1000550715 (17:36563217 G>T), RS1000557863 (17:36569287 G>A,C), RS1000683365 (17:36559329 C>A), RS1000686977 (17:36567608 T>C), RS1000720231 (17:36562029 C>T), RS1000751365 (17:36546916 C>G), RS1000756719 (17:36563606 G>T), RS1000815646 (17:36583002 A>G), RS1000841470 (17:36551182 T>G), RS1000843643 (17:36557793 A>T), RS1000846898 (17:36582714 C>G,T), RS1000901602 (17:36556373 T>C)

Disease associations

OMIM: gene MIM:612275 | disease phenotypes: MIM:616025, MIM:614526

GenCC curated gene-disease

Mondo (2): hyperphosphatasia with intellectual disability syndrome 5 (MONDO:0014457), chromosome 17q12 duplication syndrome (MONDO:0013796)

Orphanet (2): Hyperphosphatasia-intellectual disability syndrome (Orphanet:247262), 17q12 microduplication syndrome (Orphanet:261272)

HPO phenotypes

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

GWAS associations

6 associations (top):

StudyTraitp-value
GCST002783_360Body mass index8.000000e-08
GCST002783_495Body mass index2.000000e-07
GCST004904_190Body mass index5.000000e-11
GCST005316_211Intelligence (MTAG)4.000000e-10
GCST010988_60Adult body size2.000000e-14
GCST010989_21Body size at age 104.000000e-08

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0004340body mass index
EFO:0004337intelligence
EFO:0009819comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects expression, decreases expression, decreases methylation3
cobaltous chlorideincreases expression2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamidedecreases expression1
FR900359increases phosphorylation1
TAK-243increases sumoylation1
dicrotophosdecreases expression1
triphenyl phosphateaffects expression1
sodium arseniteincreases expression1
aflatoxin B2decreases methylation1
coumarinincreases phosphorylation1
di-n-butylphosphoric acidaffects expression1
K 7174increases expression1
jinfukangaffects cotreatment, decreases expression1
Resveratrolaffects cotreatment, increases expression1
Atrazineincreases expression1
Caffeinedecreases phosphorylation1
Cisplatinaffects cotreatment, decreases expression1
Formaldehydedecreases expression1
Plant Extractsaffects cotreatment, increases expression1
Ribonucleotidesaffects binding1
Smokedecreases expression1
Thiramincreases expression1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxideincreases expression1
Aflatoxin B1decreases methylation1
Cadmium Chloridedecreases expression1
Lactic Acidincreases expression1

Clinical trials (associated diseases)

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

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot