SYNJ2

Chr 6

synaptojanin 2

Also known as: INPP5H

NCBI Gene: 8871ENSG00000078269UniProt: O15056

The gene is a member of the inositol-polyphosphate 5-phosphatase family. The encoded protein interacts with the ras-related C3 botulinum toxin substrate 1, which causes translocation of the encoded protein to the plasma membrane where it inhibits clathrin-mediated endocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

0
Active trials
26
Pathogenic / LP
282
ClinVar variants
2
Pubs (1 yr)
0.7
Missense Z
0.69
LOEUF
Clinical Summary— SYNJ2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 236 VUS of 282 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.000
Z-score 3.55
OE 0.51 (0.39–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.72Z-score
OE missense 0.93 (0.88–0.99)
824 obs / 883.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.51 (0.39–0.69)
0≤0.351.4
Missense OE0.93 (0.88–0.99)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 32 / 62.2Missense obs/exp: 824 / 883.8Syn Z: -0.11
DN
DN
0.6843th %ile
GOF
0.6248th %ile
LOF
0.3164th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

282 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic2
VUS236
Likely Benign18
Benign2
24
Pathogenic
2
Likely Pathogenic
236
VUS
18
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
2
0
2
VUS
0
233
3
0
236
Likely Benign
0
11
1
6
18
Benign
0
1
1
0
2
Total0245316282

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

View in ClinVar →

SYNJ2 · 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
Landmark / reviewRecent case evidence
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