DESI2

Chr 1

desumoylating isopeptidase 2

Also known as: C1orf121, CGI-146, DeSI-2, FAM152A, PNAS-4, PPPDE1

NCBI Gene: 51029 ENSG00000121644 UniProt: Q9BSY9 OMIM: 614638

The protein functions as a deubiquitinase that removes ubiquitin chains from target proteins and exhibits palmitoyl protein thioesterase activity that removes palmitoyl groups from proteins. Mutations cause autosomal recessive neurodegeneration with brain iron accumulation, typically presenting in childhood with progressive movement disorders and cognitive decline. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Enables deubiquitinase activity and long-chain fatty acyl-CoA hydrolase activity. Predicted to be involved in macromolecule depalmitoylation and proteolysis. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.45

Clinical Summary— DESI2

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.

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ClinVar Variants

14 VUS of 21 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.848

Z-score 2.73

OE 0.09 (0.03–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.91Z-score

OE missense 0.48 (0.39–0.61)

52 obs / 107.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.45)

0≤0.351.4

Missense OE?0.48 (0.39–0.61)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 1 / 10.6Missense obs/exp: 52 / 107.9Syn Z: 0.31

ClinVar Variant Classifications

21 submitted variants in ClinVar

ClinVar

Classification Summary

VUS14

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	14	14
Likely Benign	0	0
Benign	0	0
Total	14	14

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

View in ClinVar →

95 pathogenic / likely-pathogenic (of 107) ClinVar copy-number / structural variants overlap DESI2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →