GNL3L

protein-coding

G protein nucleolar 3 like

Gene summary

The protein encoded by this gene appears to be a nucleolar GTPase that is essential for ribosomal pre-rRNA processing and cell proliferation. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

MANE transcript

NM_001184819.2

Inheritance

—

ClinVar variants

U:135B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chrX:54,530,183-54,621,521

External References & Databases

Ensembl (ENSG00000130119)

Transcript & Mutation Effects

hg38 • Region Span ~91.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GNL3L variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 74

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001184819.2. 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			7 clinvar	2 clinvar		9
missense			99 clinvar	8 clinvar		107
nonsense			8 clinvar			8
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			21 clinvar			21
Total	0	0	135	10	0	145

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001184819.2	RefSeq	NP_001171748.1	15	MANE Select
ENST00000360845.3	Ensembl	ENSP00000354091.2	15	MANE Select
NM_019067.6	RefSeq	NP_061940.1	15	Standard
ENST00000336470.8	Ensembl	ENSP00000338573.4	15	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
gnl3l	Danio rerio	Structure: posterior chamber swim bladder Quality: uninflated abnormal

Gene / Model

Organism

Observed Phenotype

gnl3l

Danio rerio

Structure: posterior chamber swim bladder

Quality: uninflated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ribosome biogenesis in eukaryotes - Homo sapiens (human)
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase

Biological Process

negative regulation of protein ubiquitination
regulation of protein stability
negative regulation of protein binding
negative regulation of telomere maintenance via telomerase
negative regulation of protein sumoylation

Molecular Function

RNA binding
protein binding
GTP binding

Cellular Component

nucleus
telomerase holoenzyme complex
nucleolus
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000336470
Coding exons: 15
Length: 30861
Individuals with no LoFs: 121086
Homozygous LoFs: 1
Heterozygous LoFs: 0
Defined: 121087
p: 0.00000413

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.36	188	248	0.757	0.0000209	3847
Missense (PolyPhen)		50	89.865	0.55639		1503
Synonymous	0.118	89	90.4	0.984	0.00000739	1093
Loss of Function	3.98	1	20.4	0.0489	0.00000142	380

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000056	0.000035	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Stabilizes TERF1 telomeric association by preventing TERF1 recruitment by PML. Stabilizes TERF1 protein by preventing its ubiquitination and hence proteasomal degradation. Does so by interfering with TERF1-binding to FBXO4 E3 ubiquitin-protein ligase. Required for cell proliferation. By stabilizing TRF1 protein during mitosis, promotes metaphase-to-anaphase transition. Stabilizes MDM2 protein by preventing its ubiquitination, and hence proteasomal degradation. By acting on MDM2, may affect TP53 activity. Required for normal processing of ribosomal pre-rRNA. Binds GTP. {ECO:0000269|PubMed:16251348, ECO:0000269|PubMed:17034816, ECO:0000269|PubMed:19487455, ECO:0000269|PubMed:21132010}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

RVIS EVS: -0.31
RVIS percentile EVS: 32.06

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.259

Gene Damage Prediction

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