UFSP2

Chr 4ADAR

UFM1 specific peptidase 2

Also known as: BHD, C4orf20, DEE106, SEMDDR

NCBI Gene: 55325ENSG00000109775UniProt: Q9NUQ7

This gene encodes a highly conserved cysteine protease. The protein cleaves two C-terminal residues from ubiquitin-fold modifier 1, a ubiquitin-like post-translational modifier protein. Activation of ubiquitin-fold modifier 1 by the encoded protein exposes a C-terminal glycine residue that allows interaction with other proteins and transfer to its target protein. An allelic variant of this gene has been associated with Beukes hip dysplasia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

Primary Disease Associations & Inheritance

?Hip dysplasia, Beukes typeMIM #142669
AD
Developmental and epileptic encephalopathy 106MIM #620028
AR
Spondyloepimetaphyseal dysplasia, Di Rocco typeMIM #617974
AD
UniProtBeukes hip dysplasia
270
ClinVar variants
122
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— UFSP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
122 Pathogenic / Likely Pathogenic· 103 VUS of 270 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.83LOEUF
pLI 0.000
Z-score 2.22
OE 0.52 (0.34–0.83)
Tolerant

Typical tolerance to LoF variation

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.
0.48Z-score
OE missense 0.92 (0.82–1.02)
235 obs / 256.5 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.0.52 (0.34–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.82–1.02)
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.1.02
0≤1.21.6
LoF obs/exp: 13 / 25.0Missense obs/exp: 235 / 256.5Syn Z: -0.12

ClinVar Variant Classifications

270 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic107
Likely Pathogenic15
VUS103
Likely Benign16
Benign7
Conflicting1
107
Pathogenic
15
Likely Pathogenic
103
VUS
16
Likely Benign
7
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
6
4
6
16
Benign
0
1
2
4
7
Conflicting
—1
Total49314110249

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.

Gene2Phenotype Curations

UFSP2-related developmental delay and epilepsy

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Hip dysplasia, Beukes type

MIM #142669

Molecular basis of disorder known

Autosomal dominant

Developmental and epileptic encephalopathy 106

MIM #620028

Molecular basis of disorder known

Autosomal recessive

Spondyloepimetaphyseal dysplasia, Di Rocco type

MIM #617974

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
VCP/p97 UFMylation stabilizes BECN1 and facilitates the initiation of autophagy.
Wang Z et al.·Autophagy
2024
Dysregulation of PD-L1 by UFMylation imparts tumor immune evasion and identified as a potential therapeutic target.
Zhou J et al.·Proc Natl Acad Sci U S A
2023
A pathogenic UFSP2 variant in an autosomal recessive form of pediatric neurodevelopmental anomalies and epilepsy.
Ni M et al.·Genet Med
2021
UFSP2-related spondyloepimetaphyseal dysplasia: A confirmatory report.
Zhang G et al.·Eur J Med Genet
2020Case report
Novel genetic causes for cerebral visual impairment.
Bosch DG et al.·Eur J Hum Genet
2016
Novel spondyloepimetaphyseal dysplasia due to UFSP2 gene mutation.
Di Rocco M et al.·Clin Genet
2018Case report
Genetic heterogeneity in epilepsy and comorbidities: insights from Pakistani families.
Yasin M et al.·BMC Neurol
2024
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