GSPT2

protein-coding

G1 to S phase transition 2, the group of SURF complex

Gene summary

This gene encodes a GTPase that belongs to the GTP-binding elongation factor family. The encoded protein is a polypeptide release factor that complexes with eukaryotic peptide chain release factor 1 to mediate translation termination. This protein may also be involved in mRNA stability.[provided by RefSeq, Mar 2010]

MANE transcript

NM_018094.5

Inheritance

ClinVar variants

P:1U:39B:11

Top phenotype

Autism

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:51,743,442-51,746,232

External References & Databases

Ensembl (ENSG00000189369)

Transcript & Mutation Effects

hg38 • Region Span ~2.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disabilityLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0001071

Submitter: G2P

intellectual disabilityLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0001071

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GSPT2 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 41

not providedTotal: 9

AutismTotal: 1

SeizureTotal: 1

GSPT2-related disorderTotal: 1

Delayed speech and language developmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018094.5. 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			1 clinvar	9 clinvar	1 clinvar	11
missense	1 clinvar		37 clinvar		1 clinvar	39
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	1	0	39	9	2	51

Highest pathogenic variant AF is 0.0000018228533

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018094.5	RefSeq	NP_060564.2	1	MANE Select
ENST00000340438.6	Ensembl	ENSP00000341247.4	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mRNA surveillance pathway - Homo sapiens (human)
Translation Factors
Eukaryotic Translation Termination
Translation
Metabolism of proteins

Biological Process

nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
cytoplasmic translational termination
translation
cell cycle

Molecular Function

RNA binding
translation release factor activity
GTPase activity
protein binding
GTP binding

Cellular Component

cytosol
translation release factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000340438
Coding exons: 1
Length: 2844
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.49	133	242	0.550	0.0000174	4121
Missense (PolyPhen)		16	79.538	0.20116		1382
Synonymous	0.637	86	93.9	0.916	0.00000709	1247
Loss of Function	3.27	0	12.4	0.00	9.30e-7	248

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	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in translation termination in response to the termination codons UAA, UAG and UGA. May play a role as a potent stimulator of the release factor activity of ETF1. Exhibits GTPase activity, which is ribosome- and ETF1-dependent. May play a role in cell cycle progression. Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. {ECO:0000269|PubMed:11524954, ECO:0000269|PubMed:15987998, ECO:0000269|PubMed:17562865}.;

Recessive Scores

pRec: 0.116

Intolerance Scores

RVIS EVS: -0.07
RVIS percentile EVS: 48.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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