GIGYF2

Chr 2

GRB10 interacting GYF protein 2

Also known as: GYF2, PARK11, PERQ2, PERQ3, TNRC15

NCBI Gene: 26058ENSG00000204120UniProt: Q6Y7W6

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]

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Primary Disease Associations & Inheritance

{Parkinson disease 11}MIM #607688
0
Active trials
8
Pubs (1 yr)
52
P/LP submissions
17%
P/LP missense
0.08
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— GIGYF2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
42 unique Pathogenic / Likely Pathogenic· 238 VUS of 471 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — GIGYF2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 8.99
OE 0.03 (0.01–0.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.24Z-score
OE missense 0.76 (0.71–0.82)
542 obs / 710.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.03 (0.01–0.08)
0≤0.351.4
Missense OE0.76 (0.71–0.82)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 3 / 100.1Missense obs/exp: 542 / 710.3Syn Z: 1.14
DN
0.2499th %ile
GOF
0.3292th %ile
LOF
0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.08

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

471 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic6
VUS238
Likely Benign76
Benign48
Conflicting12
36
Pathogenic
6
Likely Pathogenic
238
VUS
76
Likely Benign
48
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
3
32
0
36
Likely Pathogenic
1
4
1
0
6
VUS
7
179
51
1
238
Likely Benign
2
8
9
57
76
Benign
0
3
38
7
48
Conflicting
—12
Total1119713165416

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GIGYF2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients