DIS3L2

Chr 2AR

DIS3 like 3'-5' exoribonuclease 2

Also known as: FAM6A, PRLMNS, hDIS3L2

NCBI Gene: 129563ENSG00000144535UniProt: Q8IYB7OMIM: 614184

DIS3L2 encodes a 3'-5'-exoribonuclease that degrades polyuridylated RNAs, including mRNAs and miRNAs, and is essential for proper mitosis and cell proliferation regulation. Biallelic mutations cause Perlman syndrome, an autosomal recessive overgrowth disorder with neonatal onset. This gene is highly constrained against loss-of-function variants in the population.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.331 OMIM phenotype
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
32 unique Pathogenic / Likely Pathogenic· 266 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →
📖
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

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic14
VUS266
Likely Benign187
Benign4
18
Pathogenic
14
Likely Pathogenic
266
VUS
187
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
0
5
0
18
Likely Pathogenic
9
0
5
0
14
VUS
6
230
23
7
266
Likely Benign
0
2
94
91
187
Benign
0
0
4
0
4
Total2823213198489

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

View in ClinVar →

Protein Context — Lollipop Plot

DIS3L2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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