GGN

Summary

GGN (gametogenetin, HGNC:18869) is a protein-coding gene on chromosome 19q13.2, encoding Gametogenetin (Q86UU5). May be involved in spermatogenesis.

This gene is a germ cell-specific gene that encodes proteins that interact with POG (proliferation of germ cells). Alternatively spliced transcript variants of a similar mouse gene encode at least three different proteins, namely gametogenetin protein 1a, gametogenetin protein 2, and gametogenetin protein 3, which show a perinuclear, cytoplasmic, and nucleolar localization, respectively. These proteins regulate the localization of POG and may play a role in spermatogenesis.

Source: NCBI Gene 199720 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 69 (Moderate, GenCC)
• Clinical variants (ClinVar): 134 total — 2 pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_152657

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18869
Approved symbol	GGN
Name	gametogenetin
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35713, MGC33369
Ensembl gene	ENSG00000179168
Ensembl biotype	protein_coding
OMIM	609966
Entrez	199720

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000334928, ENST00000585737, ENST00000586599, ENST00000587676, ENST00000591809, ENST00000904714, ENST00000932940, ENST00000955164

RefSeq mRNA: 1 — MANE Select: NM_152657 NM_152657

CCDS: CCDS12516

Canonical transcript exons

ENST00000334928 — 4 exons

Exon	Start	End
ENSE00001334358	38385421	38387280
ENSE00002780485	38387975	38388034
ENSE00002959254	38384267	38384529
ENSE00003199976	38387761	38387822

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 96.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5734 / max 262.5315, expressed in 115 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180769	0.3667	42
180771	0.1711	44
180770	0.0356	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.19	gold quality
right testis	UBERON:0004534	95.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.84	gold quality
testis	UBERON:0000473	92.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.16	gold quality
descending thoracic aorta	UBERON:0002345	73.45	gold quality
ascending aorta	UBERON:0001496	73.35	gold quality
thoracic aorta	UBERON:0001515	73.33	gold quality
aorta	UBERON:0000947	69.17	gold quality
adult organism	UBERON:0007023	67.80	gold quality
prefrontal cortex	UBERON:0000451	67.52	gold quality
left coronary artery	UBERON:0001626	67.23	gold quality
anterior cingulate cortex	UBERON:0009835	67.01	gold quality
right coronary artery	UBERON:0001625	66.96	gold quality
right frontal lobe	UBERON:0002810	66.91	gold quality
tibial artery	UBERON:0007610	66.37	gold quality
popliteal artery	UBERON:0002250	66.34	gold quality
coronary artery	UBERON:0001621	65.74	gold quality
granulocyte	CL:0000094	64.60	gold quality
stromal cell of endometrium	CL:0002255	64.55	gold quality
gastrocnemius	UBERON:0001388	64.28	gold quality
adenohypophysis	UBERON:0002196	63.52	gold quality
Brodmann (1909) area 9	UBERON:0013540	63.25	gold quality
pancreatic ductal cell	CL:0002079	63.20	silver quality
small intestine Peyer’s patch	UBERON:0003454	62.70	gold quality
amygdala	UBERON:0001876	62.55	gold quality
neocortex	UBERON:0001950	62.54	gold quality
frontal cortex	UBERON:0001870	62.45	gold quality
small intestine	UBERON:0002108	62.39	gold quality
putamen	UBERON:0001874	62.26	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.78

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• GGN1 and GGN3, interacted with POG, regulated the localization of POG, and played a role in spermatogenesis. (PMID:12574169)
• No significant associations with fertility status were observed, suggesting that variance in the GGN gene are not a common cause of oligospermic infertility in Australian men (PMID:21114676)
• GGN played a tumor-promoting role in bladder cancer through regulation of NFkappaB/caspase3-mediated apoptosis signaling. (PMID:29412153)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ggn	ENSMUSG00000031493
rattus_norvegicus	Ggn	ENSRNOG00000023931
drosophila_melanogaster	Vajk3	FBGN0028544
drosophila_melanogaster	Vajk2	FBGN0032538
drosophila_melanogaster	nahoda	FBGN0034797
drosophila_melanogaster	Vajk4	FBGN0050101
caenorhabditis_elegans		WBGENE00007479

Paralogs (2): ZNF512B (ENSG00000196700), ZNF512 (ENSG00000243943)

Protein

Protein identifiers

Gametogenetin — Q86UU5 (reviewed: Q86UU5)

All UniProt accessions (3): Q86UU5, K7EJI6, K7ENT5

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in spermatogenesis.

Subunit / interactions. Interacts with FANCL, GGNBP1 and ZNF403/GGNBP2.

Disease relevance. Spermatogenic failure 69 (SPGF69) [MIM:619826] An autosomal recessive male infertility disorder characterized by low sperm concentrations, globozoospermia, and absence of sperm acrosome. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86UU5-1	1	yes
Q86UU5-2	2
Q86UU5-3	3

RefSeq proteins (1): NP_689870* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031400	GGN	Family

Pfam: PF15685

UniProt features (35 total): compositionally biased region 13, sequence conflict 8, region of interest 7, splice variant 5, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86UU5-F1	44.60	0.00

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): 389

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (4): double-strand break repair (GO:0006302), gamete generation (GO:0007276), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (2): ubiquitin protein ligase binding (GO:0031625), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	1
sexual reproduction	1
multicellular organismal reproductive process	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
ubiquitin-like protein ligase binding	1
binding	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GGN	FANCL	Q9NW38	831
GGN	PDCD2L	Q9BRP1	666
GGN	GGNBP2	Q9H3C7	646
GGN	OAZ3	Q9UMX2	529
GGN	CNGA3	Q16281	457
GGN	SPATA16	Q9BXB7	441
GGN	MAX	P25912	430
GGN	RTCA	O00442	425
GGN	ACRV1	P26436	404
GGN	GALNT11	Q8NCW6	399
GGN	CRISP2	P16562	389
GGN	TBPL1	P62380	363
GGN	PRM3	Q9NNZ6	363
GGN	PRKG2	Q13237	349
GGN	SPACDR	Q8IZ16	333

IntAct

59 interactions, top by confidence:

A	B	Type	Score
KRT40	GGN	psi-mi:“MI:0915”(physical association)	0.560
GGN	KRT40	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	GGN	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	GGN	psi-mi:“MI:0915”(physical association)	0.560
GGN	ABI2	psi-mi:“MI:0915”(physical association)	0.560
WWP2	GGN	psi-mi:“MI:0915”(physical association)	0.560
	GGN	psi-mi:“MI:0915”(physical association)	0.560
GGN	HOMER3	psi-mi:“MI:0915”(physical association)	0.560
GGN	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	GGN	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	GGN	psi-mi:“MI:0915”(physical association)	0.560
GGN	ZMYND19	psi-mi:“MI:0915”(physical association)	0.560
RACK1	GGN	psi-mi:“MI:0915”(physical association)	0.560
NCK2	GGN	psi-mi:“MI:0915”(physical association)	0.560
GGN	SH3KBP1	psi-mi:“MI:0915”(physical association)	0.560
GRB2	GGN	psi-mi:“MI:0915”(physical association)	0.560
BAG3	GGN	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	GGN	psi-mi:“MI:0915”(physical association)	0.560
GGN	BCAS1	psi-mi:“MI:0914”(association)	0.350
GGN	MTUS2	psi-mi:“MI:0915”(physical association)	0.000
GGN	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
GGN	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.000
GGN	GOLGA2	psi-mi:“MI:0915”(physical association)	0.000
GGN	ABI2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): GGN (Two-hybrid), GGN (Two-hybrid), GGN (Two-hybrid), GGN (Two-hybrid), GGN (Two-hybrid), GGN (Two-hybrid), GGN (Two-hybrid), GGN (Two-hybrid), GGN (Two-hybrid), GGN (Two-hybrid), GGN (Two-hybrid), GGN (Two-hybrid), GGN (Two-hybrid), CYSRT1 (Two-hybrid), WWP2 (Two-hybrid)

ESM2 similar proteins: A0A0J9YXV3, A0A172M4N0, A2VE23, A5PL33, C7EMF5, E7EW31, F1NSM7, I3L273, O15027, O48582, O55189, O55196, O97939, P0C671, P0DV77, P14138, Q14D33, Q1XI13, Q28989, Q3B7M4, Q4R729, Q5R7U0, Q5SWP3, Q62840, Q63003, Q6E0U4, Q6H236, Q6NUN9, Q6UXA7, Q7Z2K8, Q86UU5, Q8BM15, Q8K4E0, Q8K4L6, Q8N1P7, Q8N3D4, Q96D09, Q96JG9, Q9BGL9, Q9D7G9

Diamond homologs: Q66HC8, Q80WJ1, Q86UU5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	107
Likely benign	10
Benign	9

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1676198	NM_152657.4(GGN):c.1271del (p.Gly424fs)	Pathogenic
1676199	NM_152657.4(GGN):c.416_437del (p.Leu139fs)	Pathogenic

SpliceAI

419 predictions. Top by Δscore:

Variant	Effect	Δscore
19:38385601:G:C	donor_gain	0.9900
19:38387281:C:CC	acceptor_gain	0.9800
19:38387984:C:A	donor_gain	0.9800
19:38387843:C:CT	acceptor_gain	0.9700
19:38385640:T:TA	donor_gain	0.9500
19:38387279:GA:G	acceptor_gain	0.9500
19:38387757:TCA:T	donor_loss	0.9500
19:38387758:CACCG:C	donor_loss	0.9500
19:38387759:A:AC	donor_gain	0.9300
19:38387760:C:CC	donor_gain	0.9300
19:38387833:A:T	acceptor_gain	0.9300
19:38387287:A:T	acceptor_gain	0.9200
19:38387844:G:T	acceptor_gain	0.9200
19:38387286:C:CT	acceptor_gain	0.9100
19:38387832:C:CT	acceptor_gain	0.9100
19:38385607:G:C	donor_gain	0.9000
19:38387276:GGAGA:G	acceptor_gain	0.9000
19:38387972:AACCT:A	donor_loss	0.9000
19:38387973:A:T	donor_loss	0.9000
19:38387974:C:A	donor_loss	0.9000
19:38385645:A:AC	donor_gain	0.8900
19:38385646:C:CC	donor_gain	0.8900
19:38387278:AGA:A	acceptor_gain	0.8900
19:38387967:TTAC:T	donor_loss	0.8900
19:38387968:TAC:T	donor_loss	0.8900
19:38387969:ACGA:A	donor_loss	0.8900
19:38385580:C:CT	donor_gain	0.8800
19:38387827:C:CT	acceptor_gain	0.8800
19:38387983:C:CA	donor_gain	0.8800
19:38387997:C:CA	donor_gain	0.8700

AlphaMissense

4057 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:38386209:G:C	F351L	0.977
19:38386209:G:T	F351L	0.977
19:38386211:A:G	F351L	0.977
19:38386014:G:C	F416L	0.975
19:38386014:G:T	F416L	0.975
19:38386016:A:G	F416L	0.975
19:38385504:G:C	F586L	0.972
19:38385504:G:T	F586L	0.972
19:38385506:A:G	F586L	0.972
19:38386164:G:C	F366L	0.960
19:38386164:G:T	F366L	0.960
19:38386166:A:G	F366L	0.960
19:38386170:G:C	F364L	0.960
19:38386170:G:T	F364L	0.960
19:38386172:A:G	F364L	0.960
19:38384490:C:A	W627C	0.957
19:38384490:C:G	W627C	0.957
19:38384492:A:G	W627R	0.952
19:38384492:A:T	W627R	0.952
19:38386203:C:A	W353C	0.949
19:38386203:C:G	W353C	0.949
19:38386171:A:G	F364S	0.948
19:38384529:C:A	W614C	0.947
19:38384529:C:G	W614C	0.947
19:38386210:A:G	F351S	0.944
19:38386008:G:C	F418L	0.943
19:38386008:G:T	F418L	0.943
19:38386010:A:G	F418L	0.943
19:38385422:A:G	W614R	0.935
19:38385422:A:T	W614R	0.935

dbSNP variants (sampled 300 via entrez): RS1000265697 (19:38387887 T>C,G), RS1000495198 (19:38388820 G>A,C,T), RS1000674996 (19:38388072 C>A), RS1001576983 (19:38390190 G>A,T), RS1001683632 (19:38384158 T>C), RS1002040680 (19:38383901 C>A), RS1002117862 (19:38387356 T>C,G), RS1002147536 (19:38387584 C>G), RS1004589594 (19:38388254 C>A,T), RS1005241620 (19:38387332 C>A,G,T), RS1005678092 (19:38386336 G>A), RS1006689129 (19:38387534 C>A), RS1006761366 (19:38387228 C>A,T), RS1006826647 (19:38387949 C>T), RS1007030081 (19:38386970 G>A,T)

Disease associations

OMIM: gene MIM:609966 | disease phenotypes: MIM:619826

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 69	Moderate	Autosomal recessive

Mondo (1): spermatogenic failure 69 (MONDO:0030732)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012205	Globozoospermia

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

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
titanium dioxide	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Okadaic Acid	increases expression	1
S-Nitrosoglutathione	increases 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_E1KC	HyCyte HEK293T KO-hGGN	Transformed cell line	Female

Clinical trials (associated diseases)

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