DIS3L2

DIS3 like 3'-5' exoribonuclease 2, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 2:231961244-232344350

Previous symbols: [ "FAM6A" ]

Links

ENSG00000144535 ∙ NCBI:129563 ∙ OMIM:614184 ∙ HGNC:28648 ∙ Uniprot:Q8IYB7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Perlman syndrome (Definitive), mode of inheritance: AR
• Perlman syndrome (Supportive), mode of inheritance: AR
• Perlman syndrome (Strong), mode of inheritance: AR
• Perlman syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Perlman syndrome	AR	Oncologic	Individuals have a high risk of Wilms tumor, and surveillance may allow early detection and treatment, which may be beneficial	Craniofacial; Musculoskeletal; Neurologic; Oncologic; Renal	4315293; 163679; 6093533; 3024486; 10508986; 22306653; 22705997; 23486540; 23613427

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DIS3L2 gene.

• Perlman syndrome (1941 variants)
• not provided (111 variants)
• Inborn genetic diseases (48 variants)
• not specified (16 variants)
• DIS3L2-related condition (11 variants)
• Neurodevelopmental disorder (1 variants)
• Hepatoblastoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DIS3L2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			12	397	7	416
missense	1	1	979	7	7	995
nonsense	14	8	3			25
start loss			2			2
frameshift	27	10	12			49
inframe indel			23			23
splice donor/acceptor (+/-2bp)	2	17				19
splice region		1	44	81		126
non coding			34	234	28	296
Total	44	36	1065	638	42

Highest pathogenic variant AF is 0.00000660

Variants in DIS3L2

This is a list of pathogenic ClinVar variants found in the DIS3L2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-231961609-C-G		Perlman syndrome	Uncertain significance (Jan 13, 2018)
2-231961630-C-T		Perlman syndrome	Uncertain significance (Jan 13, 2018)
2-231961716-C-G		Perlman syndrome	Uncertain significance (Jan 12, 2018)
2-231961717-T-A		Perlman syndrome	Uncertain significance (Jan 12, 2018)
2-231961757-G-A		Perlman syndrome	Uncertain significance (Jan 13, 2018)
2-231961764-C-T		Perlman syndrome	Uncertain significance (Jan 12, 2018)
2-232014850-C-T		Perlman syndrome	Likely benign (Jan 13, 2018)
2-232014861-G-A		Perlman syndrome	Uncertain significance (Jan 12, 2018)
2-232014867-TCTGAG-T		Perlman syndrome	Uncertain significance (Jun 14, 2016)
2-232014876-A-G		Perlman syndrome	Uncertain significance (Aug 07, 2021)
2-232014928-A-G		Perlman syndrome	Uncertain significance (Nov 05, 2023)
2-232014928-A-T		Perlman syndrome • DIS3L2-related disorder	Uncertain significance (Jul 21, 2023)
2-232014936-T-C		Perlman syndrome	Likely benign (Sep 17, 2022)
2-232014937-C-A		Perlman syndrome	Uncertain significance (May 14, 2022)
2-232014938-C-G		Perlman syndrome	Uncertain significance (May 05, 2022)
2-232014938-C-T		Perlman syndrome	Uncertain significance (Dec 17, 2020)
2-232014941-A-G		Perlman syndrome	Uncertain significance (Mar 26, 2023)
2-232014944-A-G		Perlman syndrome	Uncertain significance (May 04, 2023)
2-232014946-A-G		Perlman syndrome	Uncertain significance (Nov 15, 2021)
2-232014947-G-C		Perlman syndrome	Uncertain significance (Aug 31, 2022)
2-232014950-T-G		Perlman syndrome	Uncertain significance (Oct 27, 2022)
2-232014954-C-T		Perlman syndrome	Likely benign (Dec 22, 2020)
2-232014955-C-T		Perlman syndrome	Uncertain significance (Oct 03, 2023)
2-232014957-C-T		Perlman syndrome	Likely benign (Nov 25, 2023)
2-232014958-C-A		Perlman syndrome	Likely benign (Oct 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DIS3L2	protein_coding	protein_coding	ENST00000325385	20	383106

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.944	0.0560	124784	0	18	124802	0.0000721

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.944	477	539	0.886	0.0000329	5782
Missense in Polyphen		126	189.62	0.66448		1938
Synonymous	-0.174	222	219	1.01	0.0000145	1729
Loss of Function	5.06	8	44.4	0.180	0.00000238	513

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000651	0.0000645
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.000338	0.000334
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.0000710	0.0000706
Middle Eastern	0.000338	0.000334
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 3'-5'-exoribonuclease that specifically recognizes RNAs polyuridylated at their 3' end and mediates their degradation. Component of an exosome-independent RNA degradation pathway that mediates degradation of both mRNAs and miRNAs that have been polyuridylated by a terminal uridylyltransferase, such as ZCCHC11/TUT4. Mediates degradation of cytoplasmic mRNAs that have been deadenylated and subsequently uridylated at their 3'. Mediates degradation of uridylated pre-let-7 miRNAs, contributing to the maintenance of embryonic stem (ES) cells. Essential for correct mitosis, and negatively regulates cell proliferation. {ECO:0000255|HAMAP-Rule:MF_03045, ECO:0000269|PubMed:23756462, ECO:0000269|PubMed:24141620}.
• Disease: DISEASE: Perlman syndrome (PRLMNS) [MIM:267000]: An autosomal recessive congenital overgrowth syndrome. Affected children are large at birth, are hypotonic, and show organomegaly, characteristic facial dysmorphisms (inverted V-shaped upper lip, prominent forehead, deep-set eyes, broad and flat nasal bridge, and low-set ears), renal anomalies (nephromegaly and hydronephrosis), frequent neurodevelopmental delay, and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumor. Histologic examination of the kidneys in affected children shows frequent nephroblastomatosis, which is a precursor lesion for Wilms tumor. {ECO:0000269|PubMed:22306653, ECO:0000269|PubMed:23486540, ECO:0000269|PubMed:23613427, ECO:0000269|PubMed:28328139}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0906

Intolerance Scores

• loftool: 0.559
• rvis_EVS: -0.28
• rvis_percentile_EVS: 33.53

Haploinsufficiency Scores

• pHI: 0.0694
• hipred: N
• hipred_score: 0.414
• ghis: 0.432

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.873

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dis3l2

Zebrafish Information Network

• Gene name: dis3l2
• Affected structure: pronephric duct opening
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: mitotic cell cycle;nuclear-transcribed mRNA catabolic process, exonucleolytic;rRNA processing;RNA catabolic process;negative regulation of cell population proliferation;miRNA catabolic process;stem cell population maintenance;nuclear-transcribed mRNA catabolic process, exonucleolytic, 3'-5';cell division;mitotic sister chromatid separation;RNA phosphodiester bond hydrolysis, exonucleolytic;polyuridylation-dependent mRNA catabolic process
• Cellular component: exosome (RNase complex);P-body;cytoplasm;polysome
• Molecular function: 3'-5'-exoribonuclease activity;magnesium ion binding;ribonuclease activity;protein binding;poly(U) RNA binding