GPN2

Summary

GPN2 (GPN-loop GTPase 2, HGNC:25513) is a protein-coding gene on chromosome 1p36.11, encoding GPN-loop GTPase 2 (Q9H9Y4). Small GTPase involved in the correct assembly of RNA polymerase RNA polymerase II and III (RNAPII and RNAPIII) complexes, ensuring their proper nuclear import. It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

Predicted to enable GTPase activity.

Source: NCBI Gene 54707 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 63 total — 1 likely-pathogenic
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_018066

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25513
Approved symbol	GPN2
Name	GPN-loop GTPase 2
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10349
Ensembl gene	ENSG00000142751
Ensembl biotype	protein_coding
Entrez	54707

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000374133, ENST00000374135, ENST00000431781, ENST00000461282, ENST00000477418, ENST00000932855

RefSeq mRNA: 1 — MANE Select: NM_018066 NM_018066

CCDS: CCDS289

Canonical transcript exons

ENST00000374135 — 5 exons

Exon	Start	End
ENSE00001462565	26889686	26890283
ENSE00001899852	26876132	26879749
ENSE00003481397	26888969	26889125
ENSE00003489087	26884160	26884290
ENSE00003679218	26885973	26886133

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 89.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.6364 / max 187.6371, expressed in 1817 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11197	29.7230	1817
11196	0.9134	410

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	89.65	gold quality
stromal cell of endometrium	CL:0002255	89.40	gold quality
left adrenal gland	UBERON:0001234	87.86	gold quality
apex of heart	UBERON:0002098	87.79	gold quality
right adrenal gland	UBERON:0001233	87.78	gold quality
lower esophagus mucosa	UBERON:0035834	87.77	gold quality
right adrenal gland cortex	UBERON:0035827	87.66	gold quality
left adrenal gland cortex	UBERON:0035825	87.31	gold quality
gastrocnemius	UBERON:0001388	87.13	gold quality
adrenal cortex	UBERON:0001235	86.94	gold quality
adrenal gland	UBERON:0002369	86.74	gold quality
rectum	UBERON:0001052	86.59	gold quality
esophagus mucosa	UBERON:0002469	86.59	gold quality
skin of leg	UBERON:0001511	86.51	gold quality
body of stomach	UBERON:0001161	86.35	gold quality
muscle of leg	UBERON:0001383	86.09	gold quality
transverse colon	UBERON:0001157	86.02	gold quality
islet of Langerhans	UBERON:0000006	85.93	gold quality
skin of abdomen	UBERON:0001416	85.78	gold quality
right lobe of thyroid gland	UBERON:0001119	85.71	gold quality
right atrium auricular region	UBERON:0006631	85.40	gold quality
popliteal artery	UBERON:0002250	85.39	gold quality
right lobe of liver	UBERON:0001114	85.37	gold quality
tibial artery	UBERON:0007610	85.37	gold quality
esophagus	UBERON:0001043	85.35	gold quality
left coronary artery	UBERON:0001626	85.22	gold quality
adrenal tissue	UBERON:0018303	85.14	gold quality
mucosa of stomach	UBERON:0001199	85.10	gold quality
minor salivary gland	UBERON:0001830	85.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting GPN2, 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-9851-3P	99.63	69.68	1110
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-3121-5P	97.30	66.62	1146
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-6839-5P	96.74	68.29	1088
HSA-MIR-378J	96.44	66.20	1020

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpn2	ENSDARG00000103127
mus_musculus	Gpn2	ENSMUSG00000028848
rattus_norvegicus	Gpn2	ENSRNOG00000007083
drosophila_melanogaster	CG10222	FBGN0036356
caenorhabditis_elegans	B0207.6	WBGENE00015029

Paralogs (2): GPN3 (ENSG00000111231), GPN1 (ENSG00000198522)

Protein

Protein identifiers

GPN-loop GTPase 2 — Q9H9Y4 (reviewed: Q9H9Y4)

Alternative names: ATP-binding domain 1 family member B

All UniProt accessions (3): Q9H9Y4, Q5JYG3, Q5JYG4

UniProt curated annotations — full annotation on UniProt →

Function. Small GTPase involved in the correct assembly of RNA polymerase RNA polymerase II and III (RNAPII and RNAPIII) complexes, ensuring their proper nuclear import.

Subunit / interactions. Heterodimers with GPN1 or GPN3. Binds to RNA polymerase II (RNAPII).

Subcellular location. Cytoplasm.

Similarity. Belongs to the GPN-loop GTPase family.

RefSeq proteins (1): NP_060536* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004130	Gpn	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030231	Gpn2	Family

Pfam: PF03029

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (27 total): binding site 13, short sequence motif 6, sequence variant 2, initiator methionine 1, chain 1, domain 1, site 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H9Y4-F1	84.60	0.55

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 78 (stabilizes the phosphate intermediate; shared with dimeric partner)

Ligand- & substrate-binding residues (13): 19; 21; 21; 22; 23; 23; 23; 24; 24; 46; 181; 181 …

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 101 (showing top): IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, BEIER_GLIOMA_STEM_CELL_DN, PU1_Q6, STONER_ESOPHAGEAL_CARCINOGENESIS_UP, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, BASAKI_YBX1_TARGETS_DN, RGAGGAARY_PU1_Q6, MODULE_95, CETS1P54_01, SCGGAAGY_ELK1_02, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, chr1p36, MODULE_49, KASLER_HDAC7_TARGETS_1_UP

GO Biological Process (0):

GO Molecular Function (5): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1

Protein interactions and networks

STRING

2129 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPN2	RPAP1	Q9BWH6	724
GPN2	SLC7A6OS	Q96CW6	667
GPN2	GPN3	Q9UHW5	652
GPN2	POLR2K	P53803	650
GPN2	POLR2B	P30876	646
GPN2	POLR2L	P52436	625
GPN2	RPAP2	Q8IXW5	625
GPN2	POLR2C	P19387	599
GPN2	TMEM35B	Q8NCS4	568
GPN2	POLR2J	P52435	567
GPN2	GPN1	Q9HCN4	531
GPN2	KY	Q8NBH2	523
GPN2	DDX42	Q86XP3	475
GPN2	POLR2E	P19388	461
GPN2	TANGO6	Q9C0B7	460
GPN2	UROS	P10746	460

IntAct

31 interactions, top by confidence:

A	B	Type	Score
POLR2J	POLR1C	psi-mi:“MI:0914”(association)	0.830
GPN2	GPN1	psi-mi:“MI:0915”(physical association)	0.800
POLR2C	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2J	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
GPN2	POLR2B	psi-mi:“MI:0914”(association)	0.640
POLR2L	POLR3A	psi-mi:“MI:0914”(association)	0.640
KLF11	GPN2	psi-mi:“MI:0915”(physical association)	0.560
POLR2J	SUPT5H	psi-mi:“MI:0914”(association)	0.530
POLR2M	BIN1	psi-mi:“MI:0914”(association)	0.530
GPN2	POLR2C	psi-mi:“MI:0914”(association)	0.530
GPN1	POLR3A	psi-mi:“MI:0914”(association)	0.530
POLR2J	MED14	psi-mi:“MI:0914”(association)	0.530
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
POLR2M	BIN1	psi-mi:“MI:0914”(association)	0.350
DOCK5	DPYSL4	psi-mi:“MI:0914”(association)	0.350
GPN2		psi-mi:“MI:0914”(association)	0.350
POLR2B	PALM3	psi-mi:“MI:0914”(association)	0.350
POLR2K	BDP1	psi-mi:“MI:0914”(association)	0.350
MYZAP	BIN1	psi-mi:“MI:0914”(association)	0.350
POLR2J2	POLR2D	psi-mi:“MI:0914”(association)	0.350
GPN1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): GPN2 (Affinity Capture-RNA), POLR2B (Affinity Capture-MS), GPN1 (Affinity Capture-MS), POLR2J (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), RPAP1 (Affinity Capture-MS), POLR2L (Affinity Capture-MS), GPN2 (Affinity Capture-MS), GPN2 (Affinity Capture-MS), GPN2 (Affinity Capture-MS), POLR2J (Affinity Capture-MS), RPAP1 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), GPN2 (Affinity Capture-MS), POLR2L (Affinity Capture-MS)

ESM2 similar proteins: A4FV58, A5GFZ6, A6H791, A6H7F2, D3ZAA9, D4A1R8, D4A7C0, E7F3I6, H1UBN0, O88618, P49004, Q02053, Q08DB4, Q4IQT8, Q4PF70, Q4QR99, Q4R4J2, Q4R579, Q4WT40, Q56XY2, Q58DD9, Q5BJ53, Q5E9M9, Q5R762, Q5RF36, Q5U300, Q5ZKI2, Q66JK4, Q66KF6, Q6NS21, Q6PUR6, Q7TMW6, Q7TSA0, Q7YRA3, Q86U10, Q8C166, Q8CHW4, Q8IXI1, Q8JZN7, Q8VEJ1

Diamond homologs: A6H7F2, D4A7C0, O14443, P0CN94, P0CN95, Q06543, Q08726, Q0P5E2, Q28I42, Q4IQT8, Q4PF70, Q4R579, Q4V7Z0, Q4WT40, Q54NK8, Q54TE7, Q56XY2, Q58DD9, Q5A0W6, Q5BJ53, Q66KF6, Q6BI59, Q6CBB5, Q6CQA6, Q6FSS0, Q6PUR6, Q6R518, Q6ZM63, Q750Q9, Q8VEJ1, Q9D3W4, Q9H9Y4, Q9UHW5, Q9UTL7, Q54C25, Q8W586, O42906, P47122, P46577, A4FUD1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
FGFR2 mutant receptor activation	6	285.5×	1e-13
Signaling by FGFR2 IIIa TM	6	225.4×	7e-13
Abortive elongation of HIV-1 transcript in the absence of Tat	7	217.2×	7e-14
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	7	178.4×	1e-13
RNA Pol II CTD phosphorylation and interaction with CE	7	178.4×	1e-13
MicroRNA (miRNA) biogenesis	6	171.3×	3e-12
mRNA Capping	7	166.5×	1e-13
Activation of HOX genes during differentiation	6	164.7×	4e-12

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase II	7	21.5×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	55
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3891299	NM_018066.4(GPN2):c.363C>A (p.His121Gln)	Likely pathogenic

SpliceAI

787 predictions. Top by Δscore:

Variant	Effect	Δscore
1:26884181:C:CA	donor_gain	1.0000
1:26884205:T:TA	donor_gain	1.0000
1:26884296:C:CT	acceptor_gain	1.0000
1:26885961:AGCC:A	donor_gain	1.0000
1:26885969:GTAC:G	donor_loss	1.0000
1:26885970:TA:T	donor_loss	1.0000
1:26885971:AC:A	donor_loss	1.0000
1:26886129:GAAGG:G	acceptor_gain	1.0000
1:26886131:AGG:A	acceptor_gain	1.0000
1:26886131:AGGC:A	acceptor_loss	1.0000
1:26886132:GG:G	acceptor_gain	1.0000
1:26886133:GC:G	acceptor_loss	1.0000
1:26886134:C:CC	acceptor_gain	1.0000
1:26886135:T:G	acceptor_loss	1.0000
1:26888968:CCCAG:C	donor_gain	1.0000
1:26888972:G:C	donor_gain	1.0000
1:26889684:AC:A	donor_gain	1.0000
1:26889685:CC:C	donor_gain	1.0000
1:26884093:T:TA	donor_gain	0.9900
1:26884288:GTC:G	acceptor_gain	0.9900
1:26884288:GTCC:G	acceptor_loss	0.9900
1:26884290:CCTG:C	acceptor_loss	0.9900
1:26884291:C:CA	acceptor_loss	0.9900
1:26884291:C:CC	acceptor_gain	0.9900
1:26884292:T:G	acceptor_loss	0.9900
1:26884297:A:T	acceptor_gain	0.9900
1:26886130:AAGG:A	acceptor_gain	0.9900
1:26888962:CTCTT:C	donor_loss	0.9900
1:26888963:TCTTA:T	donor_loss	0.9900
1:26888964:CTTAC:C	donor_loss	0.9900

AlphaMissense

2021 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:26889000:C:A	K179N	0.999
1:26889000:C:G	K179N	0.999
1:26889004:G:A	S178F	0.998
1:26889104:C:G	D145H	0.998
1:26889863:G:C	N78K	0.998
1:26889863:G:T	N78K	0.998
1:26890029:G:A	T23I	0.998
1:26889001:T:A	K179M	0.997
1:26889002:T:C	K179E	0.997
1:26889049:A:G	L163P	0.997
1:26889061:A:G	L159P	0.997
1:26889072:G:C	F155L	0.997
1:26889072:G:T	F155L	0.997
1:26889074:A:G	F155L	0.997
1:26889090:G:C	C149W	0.997
1:26889103:T:A	D145V	0.997
1:26889845:G:C	C84W	0.997
1:26890019:G:C	C26W	0.997
1:26890035:C:T	G21E	0.997
1:26890041:C:T	G19D	0.997
1:26889012:G:C	N175K	0.996
1:26889012:G:T	N175K	0.996
1:26889052:G:T	S162Y	0.996
1:26889053:A:G	S162P	0.996
1:26889059:A:G	C160R	0.996
1:26889073:A:G	F155S	0.996
1:26889092:A:G	C149R	0.996
1:26889751:C:T	E116K	0.996
1:26889755:C:A	Q114H	0.996
1:26889755:C:G	Q114H	0.996

dbSNP variants (sampled 300 via entrez): RS1000146387 (1:26879229 G>T), RS1000200887 (1:26880577 C>T), RS1000218857 (1:26881014 G>A,C,T), RS1000431171 (1:26891842 G>A), RS1000482618 (1:26879613 T>A,C), RS1000523785 (1:26890670 T>C), RS1000539022 (1:26884666 C>G), RS1000572318 (1:26891146 T>A,C), RS1000593739 (1:26892034 G>C), RS1000801237 (1:26878639 G>A), RS1001261864 (1:26883774 GA>G), RS1001490205 (1:26890244 G>A,C), RS1001524343 (1:26877449 T>G), RS1001678558 (1:26885002 A>C), RS1001789510 (1:26878010 C>T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:233400

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	Autosomal recessive

Mondo (2): Perrault syndrome 1 (MONDO:0009300), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (2): Perrault syndrome (Orphanet:2855), Perrault syndrome type 1 (Orphanet:642945)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007611_16	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	6.000000e-12

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	increases expression	2
aristolochic acid I	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Rotenone	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Aflatoxin B1	increases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder