GIGYF2

GRB10 interacting GYF protein 2

Basic information

Region (hg38): 2:232697298-232860605

Previous symbols: [ "PERQ2", "PERQ3", "TNRC15", "PARK11" ]

Links

ENSG00000204120 ∙ NCBI:26058 ∙ OMIM:612003 ∙ HGNC:11960 ∙ Uniprot:Q6Y7W6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Parkinson disease 11, autosomal dominant, susceptibility to (Moderate), mode of inheritance: AD
• Parkinson disease 11, autosomal dominant, susceptibility to (Limited), mode of inheritance: AD
• Parkinson disease 11, autosomal dominant, susceptibility to (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinson disease, autosomal dominant, 11	AD	Neurologic	Response to levodopa has been documented	Neurologic	18358451; 18923002; 19250854; 19279319; 19449032; 19482505; 19845746; 19906271; 20004041; 20044296; 20060621; 20178831; 20641165; 20816920; 22115759
The association with disease is controversial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GIGYF2 gene.

• not provided (212 variants)
• Leber congenital amaurosis 16 (52 variants)
• Inborn genetic diseases (45 variants)
• Parkinson disease 11, autosomal dominant, susceptibility to (11 variants)
• Leber congenital amaurosis (5 variants)
• not specified (3 variants)
• Snowflake vitreoretinal degeneration (2 variants)
• GIGYF2-related condition (2 variants)
• Retinal dystrophy (2 variants)
• See cases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GIGYF2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	3	8
missense			48	1	1	50
nonsense						0
start loss						0
frameshift				2		2
inframe indel				1	3	4
splice donor/acceptor (+/-2bp)			1			1
splice region			2			2
non coding		4	140	44	38	226
Total	0	4	189	53	45

Highest pathogenic variant AF is 0.00000657

Variants in GIGYF2

This is a list of pathogenic ClinVar variants found in the GIGYF2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-232734934-C-T			Benign (Jun 21, 2021)
2-232735194-A-C			Benign (Feb 22, 2020)
2-232747282-A-G			Benign (Jun 19, 2021)
2-232747331-G-T			Benign (Jun 19, 2021)
2-232747643-A-G		not specified	Uncertain significance (May 27, 2022)
2-232747646-A-G		GIGYF2-related disorder	Likely benign (Jul 10, 2019)
2-232747702-C-T		GIGYF2-related disorder	Likely benign (Jun 24, 2019)
2-232747735-A-G		GIGYF2-related disorder	Likely benign (Mar 01, 2024)
2-232747740-A-G		Parkinson disease 11, autosomal dominant, susceptibility to • not specified	Uncertain significance (Oct 17, 2023)
2-232747748-A-G		GIGYF2-related disorder	Uncertain significance (Apr 14, 2023)
2-232747847-C-T			Benign (Jun 19, 2021)
2-232747873-C-A			Benign (Jun 20, 2021)
2-232747946-C-T			Benign (Jun 19, 2021)
2-232748996-G-T		not specified	Uncertain significance (May 26, 2023)
2-232749006-A-G			Uncertain significance (Jan 20, 2022)
2-232749056-C-T		GIGYF2-related disorder	Likely benign (Mar 08, 2019)
2-232749065-T-C		not specified	Uncertain significance (Dec 19, 2023)
2-232756197-CTTTTTT-C		GIGYF2-related disorder	Likely benign (Mar 21, 2019)
2-232756304-C-T		not specified	Uncertain significance (Dec 14, 2023)
2-232756581-A-G			Benign (Jun 20, 2021)
2-232765867-G-A		Leber congenital amaurosis 16	Uncertain significance (Jan 13, 2018)
2-232765966-C-T		Leber congenital amaurosis 16	Likely benign (Jan 13, 2018)
2-232766038-C-T		Leber congenital amaurosis 16	Uncertain significance (Jan 13, 2018)
2-232766184-A-C		Leber congenital amaurosis 16	Uncertain significance (Jan 13, 2018)
2-232766310-A-T		Leber congenital amaurosis 16	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GIGYF2	protein_coding	protein_coding	ENST00000409451	28	163277

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.38e-14	118243	334	7171	125748	0.0303

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.24	542	710	0.763	0.0000410	8613
Missense in Polyphen		141	230.13	0.6127		2796
Synonymous	1.14	225	248	0.908	0.0000132	2421
Loss of Function	8.99	3	100	0.0300	0.00000638	968

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0527	0.0521
Ashkenazi Jewish	0.0136	0.0131
East Asian	0.129	0.0992
Finnish	0.0452	0.0419
European (Non-Finnish)	0.0138	0.0127
Middle Eastern	0.129	0.0992
South Asian	0.0579	0.0532
Other	0.0252	0.0224

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.698
• hipred: Y
• hipred_score: 0.809
• ghis: 0.627

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.775

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gigyf2
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: gigyf2
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: edematous

Gene ontology

• Biological process: feeding behavior;adult locomotory behavior;post-embryonic development;posttranscriptional gene silencing;negative regulation of translation;spinal cord motor neuron differentiation;mitotic G1 DNA damage checkpoint;multicellular organism growth;cellular protein metabolic process;insulin-like growth factor receptor signaling pathway;homeostasis of number of cells within a tissue;musculoskeletal movement;neuromuscular process controlling balance;mRNA destabilization
• Cellular component: endosome;endoplasmic reticulum;Golgi apparatus;cytosol;cytoplasmic stress granule;membrane;integral component of membrane;protein-containing complex;perikaryon;proximal dendrite
• Molecular function: RNA binding;protein binding;cadherin binding;proline-rich region binding