NUGGC

Summary

NUGGC (nuclear GTPase, germinal center associated, HGNC:33550) is a protein-coding gene on chromosome 8p21.1, encoding Nuclear GTPase SLIP-GC (Q68CJ6). Nuclear GTPase found in germinal center B-cells, where it may inhibit function of the activation-induced cytidine deaminase AICDA.

Enables GTPase activity. Involved in cellular response to lipopolysaccharide; negative regulation of apoptotic process; and regulation of nuclear cell cycle DNA replication. Located in cytosol and nuclear speck.

Source: NCBI Gene 389643 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 150 total
• MANE Select transcript: NM_001010906

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33550
Approved symbol	NUGGC
Name	nuclear GTPase, germinal center associated
Location	8p21.1
Locus type	gene with protein product
Status	Approved
Aliases	HMFN0672, SLIP-GC
Ensembl gene	ENSG00000189233
Ensembl biotype	protein_coding
OMIM	619088
Entrez	389643

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000413272, ENST00000418860, ENST00000952401, ENST00000952402

RefSeq mRNA: 1 — MANE Select: NM_001010906 NM_001010906

CCDS: CCDS47833

Canonical transcript exons

ENST00000413272 — 19 exons

Exon	Start	End
ENSE00001366794	28026962	28027052
ENSE00001378623	28030310	28030418
ENSE00001382143	28031243	28031381
ENSE00001382566	28029266	28029402
ENSE00001484699	28033540	28033697
ENSE00001484701	28041051	28041215
ENSE00001484703	28045527	28045660
ENSE00001484704	28047507	28047612
ENSE00001484705	28055965	28056054
ENSE00001484707	28060426	28060601
ENSE00001484709	28064522	28064731
ENSE00001484710	28067514	28067744
ENSE00001484713	28068216	28068438
ENSE00001484716	28069544	28069652
ENSE00001484718	28070252	28070356
ENSE00001484722	28074368	28074456
ENSE00001484724	28083775	28083936
ENSE00001686259	28058258	28058276
ENSE00001755704	28021964	28023462

Expression profiles

Bgee: expression breadth broad, 96 present calls, max score 82.84.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5082 / max 108.0019, expressed in 97 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92523	0.2629	80
92522	0.2395	70
92521	0.0058	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
liver	UBERON:0002107	82.84	gold quality
right lobe of liver	UBERON:0001114	80.28	gold quality
lymph node	UBERON:0000029	79.71	gold quality
bone marrow cell	CL:0002092	79.24	gold quality
thymus	UBERON:0002370	77.40	silver quality
quadriceps femoris	UBERON:0001377	76.86	gold quality
vermiform appendix	UBERON:0001154	73.73	gold quality
tonsil	UBERON:0002372	72.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.76	gold quality
cerebellar vermis	UBERON:0004720	72.57	gold quality
duodenum	UBERON:0002114	66.23	gold quality
bone marrow	UBERON:0002371	66.07	gold quality
granulocyte	CL:0000094	65.27	gold quality
spleen	UBERON:0002106	64.70	gold quality
sural nerve	UBERON:0015488	64.39	gold quality
rectum	UBERON:0001052	63.72	gold quality
adult mammalian kidney	UBERON:0000082	62.71	gold quality
colonic epithelium	UBERON:0000397	62.67	silver quality
blood	UBERON:0000178	60.26	gold quality
kidney	UBERON:0002113	59.74	gold quality
right lobe of thyroid gland	UBERON:0001119	59.33	gold quality
thyroid gland	UBERON:0002046	58.47	gold quality
left lobe of thyroid gland	UBERON:0001120	58.31	gold quality
small intestine	UBERON:0002108	57.60	gold quality
urinary bladder	UBERON:0001255	57.44	gold quality
small intestine Peyer’s patch	UBERON:0003454	56.86	gold quality
saliva-secreting gland	UBERON:0001044	55.91	gold quality
minor salivary gland	UBERON:0001830	55.35	gold quality
transverse colon	UBERON:0001157	55.16	gold quality
mucosa of transverse colon	UBERON:0004991	54.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.13
E-MTAB-5061	no	2.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting NUGGC, 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-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428

Literature-anchored findings (GeneRIF, showing 1)

• SLIP-GC is a replication-related protein in germinal center B cells whose reduction is toxic to cells through an AICDA-dependent mechanism. (PMID:19734146)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nuggc.3	ENSDARG00000058672
danio_rerio	nuggc.1	ENSDARG00000071001
danio_rerio	nuggc.2	ENSDARG00000091951
danio_rerio	si:dkeyp-85e10.3	ENSDARG00000092878

Protein

Protein identifiers

Nuclear GTPase SLIP-GC — Q68CJ6 (reviewed: Q68CJ6)

Alternative names: Speckled-like pattern in the germinal center

All UniProt accessions (2): C9JSP2, Q68CJ6

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear GTPase found in germinal center B-cells, where it may inhibit function of the activation-induced cytidine deaminase AICDA. Reduces somatic hypermutation in B-cells which may enhance genome stability.

Subcellular location. Nucleus speckle.

Tissue specificity. Expressed in germinal center B-cell and in lymphomas derived from germinal center B-cell.

RefSeq proteins (1): NP_001010906* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR045063	Dynamin_N	Domain
IPR053082	Nuclear_GTPase_SLIP-GC	Family

Pfam: PF00350

UniProt features (11 total): sequence variant 5, coiled-coil region 2, chain 1, region of interest 1, compositionally biased region 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68CJ6-F1	78.46	0.26

Functional residue map

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

Ligand- & substrate-binding residues (1): 107–114

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 53 (showing top): GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELL_CYCLE_DNA_REPLICATION, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_NUCLEAR_CELL_CYCLE_DNA_REPLICATION, chr8p21, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_DNA_REPLICATION, GOBP_RESPONSE_TO_MOLECULE_OF_BACTERIAL_ORIGIN, GOCC_NUCLEAR_SPECK

GO Biological Process (3): regulation of nuclear cell cycle DNA replication (GO:0033262), negative regulation of apoptotic process (GO:0043066), cellular response to lipopolysaccharide (GO:0071222)

GO Molecular Function (4): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear speck (GO:0016607), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of cell cycle process	1
nuclear DNA replication	1
regulation of DNA-templated DNA replication	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
nuclear lumen	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

832 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUGGC	NUTM2G	Q5VZR2	625
NUGGC	RTL9	Q8NET4	541
NUGGC	RHEX	Q6ZWK4	459
NUGGC	MAP7D2	Q96T17	452
NUGGC	RALGPS1	Q5JS13	450
NUGGC	RFTN2	Q52LD8	450
NUGGC	EFR3B	Q9Y2G0	420
NUGGC	LAX1	Q8IWV1	416
NUGGC	C16orf54	Q6UWD8	414
NUGGC	AICDA	Q9GZX7	385
NUGGC	MANSC1	Q9H8J5	383
NUGGC	ZC3H7B	Q9UGR2	374
NUGGC	MS4A1	P08984	374
NUGGC	PDCL2	Q8N4E4	370
NUGGC	RGS13	O14921	366

IntAct

2 interactions, top by confidence:

A	B	Type	Score
NUGGC	POLD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): FEM1B (Affinity Capture-MS), POLD2 (Affinity Capture-MS), NUGGC (Affinity Capture-MS)

ESM2 similar proteins: A1E2I4, A2CI34, A7VK00, D3YWJ0, F1M649, O18412, O95140, P18588, P18589, P18590, P20591, P20592, P33237, Q1MT80, Q20CR4, Q23424, Q28379, Q3UP24, Q4ADG6, Q4ADG7, Q4ADG8, Q4TVR5, Q4VSN1, Q4VSN2, Q4VSN3, Q4VSN4, Q4VSN5, Q5R5G3, Q67E00, Q67E01, Q68CJ6, Q6NVF4, Q6P3V7, Q6Q899, Q6XUX0, Q6XUX1, Q6XUX2, Q6XUX3, Q6ZSC3, Q7YU24

Diamond homologs: D3YWJ0, Q68CJ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	114
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3424 predictions. Top by Δscore:

Variant	Effect	Δscore
8:28026957:TTTA:T	donor_loss	1.0000
8:28026958:TTACC:T	donor_loss	1.0000
8:28026959:TACCT:T	donor_loss	1.0000
8:28026960:ACC:A	donor_loss	1.0000
8:28026961:C:CA	donor_loss	1.0000
8:28027049:CAGT:C	acceptor_gain	1.0000
8:28027051:GT:G	acceptor_gain	1.0000
8:28027053:C:CC	acceptor_gain	1.0000
8:28027055:A:AC	acceptor_gain	1.0000
8:28027055:A:C	acceptor_gain	1.0000
8:28030414:CTTAT:C	acceptor_gain	1.0000
8:28031238:CGTA:C	donor_loss	1.0000
8:28031239:GTAC:G	donor_loss	1.0000
8:28031241:ACCT:A	donor_gain	1.0000
8:28031242:C:CG	donor_loss	1.0000
8:28031242:CCTC:C	donor_gain	1.0000
8:28031244:T:TA	donor_gain	1.0000
8:28041050:CCA:C	donor_gain	1.0000
8:28041216:C:CC	acceptor_gain	1.0000
8:28047505:AC:A	donor_gain	1.0000
8:28047506:CC:C	donor_gain	1.0000
8:28060420:CAATA:C	donor_loss	1.0000
8:28060422:ATACC:A	donor_loss	1.0000
8:28060423:TACC:T	donor_loss	1.0000
8:28060425:C:A	donor_loss	1.0000
8:28060598:TGGT:T	acceptor_gain	1.0000
8:28064517:GTCAC:G	donor_loss	1.0000
8:28064518:TCACC:T	donor_loss	1.0000
8:28064519:CACCT:C	donor_loss	1.0000
8:28064520:A:C	donor_loss	1.0000

AlphaMissense

5256 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:28030327:A:G	L667P	0.984
8:28068430:A:G	L89P	0.982
8:28068242:C:G	A152P	0.981
8:28033652:A:G	C553R	0.978
8:28067741:A:G	W162R	0.978
8:28067741:A:T	W162R	0.978
8:28045580:C:G	A465P	0.977
8:28033658:C:G	A551P	0.976
8:28069598:A:G	L68P	0.973
8:28033654:A:T	V552D	0.967
8:28033674:A:C	F545L	0.965
8:28033674:A:T	F545L	0.965
8:28033676:A:G	F545L	0.965
8:28067728:A:G	L166P	0.964
8:28068354:G:C	S114R	0.964
8:28068354:G:T	S114R	0.964
8:28068356:T:G	S114R	0.964
8:28064530:A:G	W305R	0.963
8:28064530:A:T	W305R	0.963
8:28029311:A:C	F703L	0.962
8:28029311:A:T	F703L	0.962
8:28029313:A:G	F703L	0.962
8:28033650:G:C	C553W	0.962
8:28069619:A:G	L61S	0.959
8:28069608:A:C	Y65D	0.958
8:28023429:A:G	L760P	0.956
8:28033639:C:A	G557V	0.954
8:28033659:T:A	K550N	0.954
8:28033659:T:G	K550N	0.954
8:28033663:A:G	L549P	0.953

dbSNP variants (sampled 300 via entrez): RS1000011658 (8:28066348 T>G), RS1000057778 (8:28056136 C>A), RS1000096130 (8:28058327 C>A,G), RS1000138002 (8:28028833 C>A), RS1000173434 (8:28067195 G>T), RS1000308304 (8:28034045 G>A), RS1000367926 (8:28023929 G>A), RS1000518585 (8:28039613 A>G), RS1000531390 (8:28066710 T>A), RS1000564652 (8:28084180 G>A,C,T), RS1000571876 (8:28033760 T>C), RS1000658 (8:28048082 T>C), RS1000692706 (8:28045203 C>T), RS1000698670 (8:28057166 A>T), RS1000743291 (8:28078597 C>A)

Disease associations

OMIM: gene MIM:619088 | 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
GCST001776_4	Cardiac Troponin-T levels	4.000000e-06
GCST009030_8	Venous thromboembolism	2.000000e-09
GCST010725_67	Malaria	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005043	cardiac troponin T measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases mutagenesis, affects methylation, decreases expression	4
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
benzo(e)pyrene	increases methylation	1
monomethylpropion	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
licochalcone B	increases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	decreases methylation	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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