UFSP2

Chr 4ADAR

UFM1 specific peptidase 2

Also known as: BHD, C4orf20, DEE106, SEMDDR

The protein is a thiol-dependent isopeptidase that cleaves UFM1 (ubiquitin-fold modifier 1) from conjugated target proteins and processes UFM1 precursors, playing a critical role in cellular protein modification and ribosome recycling. Mutations cause developmental and epileptic encephalopathy, spondyloepimetaphyseal dysplasia, and Beukes hip dysplasia, affecting both neurological development and skeletal systems. The gene shows extreme intolerance to loss-of-function variants (pLI near 1.0) and follows both autosomal dominant and autosomal recessive inheritance patterns.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
AD/ARLOEUF 0.833 OMIM phenotypes
Clinical SummaryUFSP2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
122 unique Pathogenic / Likely Pathogenic· 103 VUS of 271 total submissions
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GeneReview available — UFSP2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.000
Z-score 2.22
OE 0.52 (0.340.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.48Z-score
OE missense 0.92 (0.821.02)
235 obs / 256.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.52 (0.340.83)
00.351.4
Missense OE0.92 (0.821.02)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 13 / 25.0Missense obs/exp: 235 / 256.5Syn Z: -0.12

ClinVar Variant Classifications

271 submitted variants in ClinVar

Classification Summary

Pathogenic107
Likely Pathogenic15
VUS103
Likely Benign18
Benign6
Conflicting1
107
Pathogenic
15
Likely Pathogenic
103
VUS
18
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
3
103
0
107
Likely Pathogenic
1
4
10
0
15
VUS
2
79
22
0
103
Likely Benign
0
7
4
7
18
Benign
0
0
2
4
6
Conflicting
1
Total49314111250

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

View in ClinVar →

Protein Context — Lollipop Plot

UFSP2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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