DIS3L2

Chr 2AR

DIS3 like 3'-5' exoribonuclease 2

Also known as: FAM6A, PRLMNS, hDIS3L2

NCBI Gene: 129563ENSG00000144535UniProt: Q8IYB7

The protein encoded by this gene is similar in sequence to 3'/5' exonucleolytic subunits of the RNA exosome. The exosome is a large multimeric ribonucleotide complex responsible for degrading various RNA substrates. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Mar 2012]

Primary Disease Associations & Inheritance

Perlman syndromeMIM #267000
AR
0
Active trials
28
Pathogenic / LP
389
ClinVar variants
15
Pubs (1 yr)
0.9
Missense Z
0.33
LOEUF· LoF intolerant
Clinical Summary— DIS3L2
🧬
Gene-Disease Validity (ClinGen)
Perlman syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 284 VUS of 389 total submissions
📖
GeneReview available — DIS3L2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.944
Z-score 5.06
OE 0.18 (0.10–0.33)
Highly constrained

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

Missense Constraint
0.94Z-score
OE missense 0.89 (0.82–0.95)
477 obs / 538.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.10–0.33)
0≤0.351.4
Missense OE0.89 (0.82–0.95)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 8 / 44.4Missense obs/exp: 477 / 538.7Syn Z: -0.17

ClinVar Variant Classifications

389 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic11
VUS284
Likely Benign71
Benign2
Conflicting4
17
Pathogenic
11
Likely Pathogenic
284
VUS
71
Likely Benign
2
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
8
0
17
Likely Pathogenic
4
0
7
0
11
VUS
5
240
36
3
284
Likely Benign
0
1
33
37
71
Benign
0
0
2
0
2
Conflicting
—4
Total182418640389

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

View in ClinVar →

DIS3L2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DIS3L2-related Perlman syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients