GGN

protein-coding

gametogenetin

Gene summary

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_152657.4

Inheritance

ClinVar variants

P:2U:108B:20

Top phenotype

Spermatogenic failure 69

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr19:38,384,267-38,388,082

External References & Databases

Ensembl (ENSG00000179168)

Transcript & Mutation Effects

hg38 • Region Span ~3.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 69MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030732

Submitter: PanelApp Australia

spermatogenic failure 69LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030732

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spermatogenic failure 69AR

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 31985809; 33108537

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GGN variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 112

not providedTotal: 20

GGN-related disorderTotal: 3

Spermatogenic failure 69Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152657.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar		5
missense			107 clinvar	7 clinvar	7 clinvar	121
nonsense					1 clinvar	1
start loss						0
frameshift	2 clinvar		1 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	2	0	108	12	8	130

Highest pathogenic variant AF is 0.000008089286

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152657.4	RefSeq	NP_689870.3	2	MANE Select
ENST00000334928.11	Ensembl	ENSP00000334940.5	2	MANE Select
ENST00000585737.1	Ensembl	ENSP00000467295.1	2	Standard
ENST00000586599.1	Ensembl	ENSP00000467084.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

double-strand break repair
gamete generation
spermatogenesis
embryo implantation
protein localization

Molecular Function

protein binding
ubiquitin protein ligase binding
protein dimerization activity

Cellular Component

nucleolus
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000334928
Coding exons: 2
Length: 3818
Individuals with no LoFs: 125686
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125726
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.395	399	422	0.946	0.0000305	3912
Missense (PolyPhen)		49	61.421	0.79777		523
Synonymous	2.79	159	210	0.755	0.0000167	1581
Loss of Function	2.03	7	15.7	0.447	9.17e-7	153

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000085	0.000062	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00017	0.00016	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00017	0.00015	rare
South Asian	0.00024	0.00023	rare
Other	0.00019	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in spermatogenesis. {ECO:0000250}.;

Recessive Scores

pRec: 0.114

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0208

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium