GeneBe

GIGYF2

protein-coding

GRB10 interacting GYF protein 2

Gene summary

This gene contains CAG trinucleotide repeats and encodes a protein containing several stretches of polyglutamine residues. The encoded protein may be involved in the regulation of tyrosine kinase receptor signaling. This gene is located in a chromosomal region that was genetically linked to Parkinson disease type 11, and mutations in this gene were thought to be causative for this disease. However, more recent studies in different populations have been unable to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

Previous symbols:
  • PERQ2
  • PERQ3
  • TNRC15
  • PARK11

MANE transcript

NM_001103146.3

Inheritance

AD

ClinVar variants

P:2U:189B:41

Top phenotype

Parkinson disease, autosomal dominant, 11

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr2:232,697,299-232,860,605

External References & Databases

Ensembl (ENSG00000204120)NCBI Gene (26058)OMIM (612003)HGNC:11960GenCCUniProt (Q6Y7W6)AlphaFoldClinVar (GIGYF2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~163.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Parkinson disease 11, autosomal dominant, susceptibility toLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0011896

Submitter: Ambry Genetics

Parkinson disease 11, autosomal dominant, susceptibility toLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0011896

Submitter: Labcorp Genetics (formerly Invitae)

Parkinson disease 11, autosomal dominant, susceptibility toLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0011896

Submitter: PanelApp Australia

Parkinson disease 11, autosomal dominant, susceptibility toMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0011896

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Parkinson disease, autosomal dominant, 11AD

Manifestation: Neurologic

Intervention: Neurologic

Rationale: Response to levodopa has been documented

Comments: The association with disease is controversial

Refs: 18358451; 18923002; 19250854; 19279319; 19449032; 19482505; 19845746; 19906271; 20004041; 20044296; 20060621; 20178831; 20641165; 20816920; 22115759Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GIGYF2 variants in ClinVar

13 Conditions Cataloged
not providedTotal: 278
not specifiedTotal: 196
Leber congenital amaurosis 16Total: 56
GIGYF2-related disorderTotal: 39
Parkinson disease 11, autosomal dominant, susceptibility toTotal: 14
Snowflake vitreoretinal degenerationTotal: 7
KCNJ13-related disordersTotal: 5
KCNJ13-related conditionTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001103146.3. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
26
clinvar
4
clinvar
 33
missense
1
clinvar
164
clinvar
10
clinvar
1
clinvar
 176
nonsense
1
clinvar
6
clinvar
 7
start loss
0
frameshift
3
clinvar
 3
splice donor/acceptor (+/-2bp)
13
clinvar
 13
Total11189365232

Highest pathogenic variant AF is 0.000059382986

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 133 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001103146.3RefSeqNP_001096616.127MANE Select
ENST00000373563.9EnsemblENSP00000362664.527MANE Select
NM_001103147.2RefSeqNP_001096617.128Standard
NM_001103148.2RefSeqNP_001096618.127Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
gigyf2Danio rerio

Structure: head

Quality: edematous

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • feeding behavior
  • adult locomotory behavior
  • post-embryonic development
  • posttranscriptional gene silencing
  • negative regulation of translation

Molecular Function

  • RNA binding
  • protein binding
  • cadherin binding
  • proline-rich region binding

Cellular Component

  • endosome
  • endoplasmic reticulum
  • Golgi apparatus
  • cytosol
  • cytoplasmic stress granule

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000409451
Coding exons
28
Length
163277
Individuals with no LoFs
118243
Homozygous LoFs
334
Heterozygous LoFs
7171
Defined
125748
p
0.0303
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.245427100.7630.00004108613
Missense (PolyPhen)141230.130.61272796
Synonymous1.142252480.9080.00001322421
Loss of Function8.9931000.03000.00000638968

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00390.0033notable
Latino/Admixed American0.0490.046notable
Ashkenazi Jewish0.0140.013notable
East Asian0.130.099notable
Finnish0.0450.042notable
European (Non-Finnish)0.0140.013notable
South Asian0.0580.053notable
Other0.0250.022notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Key component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation (PubMed:22751931). In 4EHP-GYF2 the complex, acts as a factor that bridges EIF4E2 to ZFP36/TTP, linking translation repression with mRNA decay (By similarity). May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling, including IGF1 and insulin receptors (PubMed:12771153). {ECO:0000250|UniProtKB:Q6Y7W8, ECO:0000269|PubMed:12771153, ECO:0000269|PubMed:22751931}.;
Disease
DISEASE: Parkinson disease 11 (PARK11) [MIM:607688]: A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. {ECO:0000269|PubMed:18358451, ECO:0000269|PubMed:20060621, ECO:0000269|PubMed:20178831, ECO:0000269|PubMed:26134514}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry. Its association with Parkinson disease is however unclear. According to a number of studies, variations affecting this gene are not a frequent cause of Parkinson disease, suggesting that GIGYF2 does not play a major role in Parkinson disease etiology (PubMed:19279319, PubMed:19429085, PubMed:19638301, PubMed:19482505, PubMed:20004041, PubMed:19321232, PubMed:20060621). {ECO:0000269|PubMed:19279319, ECO:0000269|PubMed:19321232, ECO:0000269|PubMed:19429085, ECO:0000269|PubMed:19482505, ECO:0000269|PubMed:19638301, ECO:0000269|PubMed:20004041, ECO:0000269|PubMed:20060621}.;

Recessive Scores

pRec
0.110

Intolerance Scores

LoFtool
0.446
RVIS EVS
-1.15
RVIS percentile EVS
6.33

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
N
Essential (gene trap)
K
Indispensability pred.
E
Indispensability score
0.775

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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