SYNRG

Chr 17

synergin gamma

Also known as: AP1GBP1, SYNG

NCBI Gene: 11276ENSG00000275066UniProt: Q9UMZ2

This gene encodes a protein that interacts with the gamma subunit of AP1 clathrin-adaptor complex. The AP1 complex is located at the trans-Golgi network and associates specific proteins with clathrin-coated vesicles. This encoded protein may act to connect the AP1 complex to other proteins. Alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

329
ClinVar variants
133
Pathogenic / LP
0.93
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SYNRG
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
133 Pathogenic / Likely Pathogenic· 170 VUS of 329 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.32LOEUF
pLI 0.931
Z-score 5.65
OE 0.19 (0.12–0.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.44Z-score
OE missense 0.85 (0.79–0.91)
583 obs / 689.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.12–0.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.79–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 11 / 57.0Missense obs/exp: 583 / 689.2Syn Z: 0.30

ClinVar Variant Classifications

329 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic119
Likely Pathogenic14
VUS170
Likely Benign24
Benign2
119
Pathogenic
14
Likely Pathogenic
170
VUS
24
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
119
0
119
Likely Pathogenic
0
0
14
0
14
VUS
1
157
12
0
170
Likely Benign
0
16
2
6
24
Benign
0
1
0
1
2
Total11741477329

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

View in ClinVar →

Protein Context — Lollipop Plot

SYNRG · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SYNERGIN, GAMMA; SYNRG
MIM #607291 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Variation in the management of isolated craniosynostosis: a survey of the Synostosis Research Group.
Kestle JRW et al.·J Neurosurg Pediatr
2018
ZNF384-Related Fusion Genes in Acute Lymphoblastic Leukemia.
Zhu L et al.·Cancer Control
2023Review
Evaluation of 3,606 renal cell tumors for TFE3 rearrangements and TFEB alterations via fluorescence in situ hybridization, next generation sequencing, and GPNMB immunohistochemistry.
Whaley RD et al.·Hum Pathol
2025
Interacting with AP1 complex mutated synergin gamma (SYNRG) reveals a novel coatopathy in the form of complicated hereditary spastic paraplegia.
Ayaz A et al.·Brain Dev
2022
Management of sagittal synostosis in the Synostosis Research Group: baseline data and early outcomes.
Baker CM et al.·Neurosurg Focus
2021
Identification of a Risk Allele at SLC41A3 and a Protective Allele HLA-DPB1*02:01 Associated with Sarcopenia in Japanese.
Furutani M et al.·Gerontology
2025
Prenatal diagnosis and perinatal findings of 17q12 microdeletion encompassing HNF1B in a fetus with bilateral hyperechogenic kidneys on fetal ultrasound and mild renal abnormality after birth, and a review of the literature of prenatal diagnosis of 17q12 microdeletion.
Chen CP et al.·Taiwan J Obstet Gynecol
2024Review
FISH combined with RT-PCR facilitates classification of Chinese adult patients with B-other ALL through improved identification of ZNF384 rearrangement.
Li Q et al.·Leuk Lymphoma
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools