SYNJ2

Chr 6

synaptojanin 2

NCBI Gene: 8871 ENSG00000078269 OMIM: 609410

The protein is an inositol 5-phosphatase that inhibits clathrin-mediated endocytosis at the plasma membrane and participates in membrane trafficking pathways. Mutations cause autosomal recessive early-onset parkinsonism with additional neurological features including dystonia and cognitive impairment. This gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.69

Clinical Summary— SYNJ2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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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 OE?0.51 (0.39–0.69)

0≤0.351.4

Missense OE?0.93 (0.88–0.99)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 32 / 62.2Missense obs/exp: 824 / 883.8Syn Z: -0.11

This gene — mechanism propensity

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.