SENP2

Chr 3

SUMO specific peptidase 2

Also known as: AXAM2, SMT3IP2

NCBI Gene: 59343 ENSG00000163904 UniProt: Q9HC62

SUMO1 (UBL1; MIM 601912) is a small ubiquitin-like protein that can be covalently conjugated to other proteins. SENP2 is one of a group of enzymes that process newly synthesized SUMO1 into the conjugatable form and catalyze the deconjugation of SUMO1-containing species.[supplied by OMIM, Apr 2004]

Research

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.30

Clinical Summary— SENP2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

68 VUS of 91 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.983

Z-score 4.88

OE 0.15 (0.08–0.30)

Highly constrained

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

Missense Constraint?

1.87Z-score

OE missense 0.70 (0.63–0.79)

221 obs / 314.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.08–0.30)

0≤0.351.4

Missense OE?0.70 (0.63–0.79)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 6 / 38.8Missense obs/exp: 221 / 314.2Syn Z: 0.56

This gene — mechanism propensity

0.4289th %ile

GOF

0.3491th %ile

LOF

0.68top 10%

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

LOFprediction above median · LOEUF 0.30

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

91 submitted variants in ClinVar

ClinVar

Classification Summary

VUS68

Likely Benign3

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	68	0	0	68
Likely Benign	1	1	1	3
Benign	2	0	0	2
Total	71	1	1	73

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

View in ClinVar →

44 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap SENP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →