PAN2

poly(A) specific ribonuclease subunit PAN2, the group of Exonucleases|Ubiquitin specific peptidases|WD repeat domain containing

Basic information

Region (hg38): 12:56316223-56334053

Previous symbols: [ "USP52" ]

Links

ENSG00000135473 ∙ NCBI:9924 ∙ OMIM:617447 ∙ HGNC:20074 ∙ Uniprot:Q504Q3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple congenital anomalies/dysmorphic syndrome-intellectual disability (Definitive), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAN2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAN2 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					1	1
missense			60	1	1	62
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	62	1	2

Variants in PAN2

This is a list of pathogenic ClinVar variants found in the PAN2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-56317640-G-A		not specified	Uncertain significance (Sep 01, 2021)
12-56318257-T-C		not specified	Uncertain significance (Nov 22, 2023)
12-56318321-G-A		not specified	Uncertain significance (Oct 29, 2021)
12-56318389-C-T		not specified	Uncertain significance (Jun 16, 2022)
12-56318390-G-A		not specified	Uncertain significance (Aug 08, 2022)
12-56318399-C-CA		PAN2-related multiple congenital anomalies syndrome	Likely pathogenic (Feb 16, 2022)
12-56318416-T-C			Uncertain significance (Feb 28, 2023)
12-56318417-C-T		not specified	Uncertain significance (Nov 22, 2023)
12-56319373-T-C		not specified	Uncertain significance (Feb 05, 2024)
12-56319408-G-C		not specified	Uncertain significance (Nov 15, 2024)
12-56319667-T-C		not specified	Uncertain significance (Feb 06, 2024)
12-56319708-C-A		not specified	Uncertain significance (Jan 23, 2023)
12-56319748-C-T		not specified	Uncertain significance (Feb 12, 2024)
12-56319749-G-A		not specified	Uncertain significance (Oct 13, 2023)
12-56319865-T-C			Uncertain significance (Apr 29, 2024)
12-56319895-C-A		See cases	Uncertain significance (Mar 02, 2023)
12-56319909-A-C		not specified	Uncertain significance (Mar 23, 2022)
12-56319917-G-A		not specified	Uncertain significance (Aug 08, 2022)
12-56319970-C-T		not specified	Uncertain significance (Oct 25, 2023)
12-56320013-G-A		not specified	Uncertain significance (Jun 10, 2024)
12-56322435-T-A		not specified	Uncertain significance (Dec 26, 2023)
12-56322479-C-T		not specified	Uncertain significance (Oct 20, 2021)
12-56322622-C-T		not specified	Uncertain significance (Jan 26, 2022)
12-56322670-CCT-C		PAN2-related disorder	Uncertain significance (Nov 30, 2023)
12-56322683-C-A		not specified	Uncertain significance (Aug 21, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAN2	protein_coding	protein_coding	ENST00000425394	25	17831

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.936	0.0640	125721	0	27	125748	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.18	448	681	0.658	0.0000383	7912
Missense in Polyphen		126	254.05	0.49596		2760
Synonymous	1.36	224	251	0.891	0.0000134	2369
Loss of Function	5.86	12	61.6	0.195	0.00000341	681

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000242	0.000242
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.00	0.00
South Asian	0.000200	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in general and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A) tails of RNA and the activity is stimulated by poly(A)-binding protein (PABP). PAN deadenylation is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA decaping and subsequent 5'-3' exonucleolytic degradation by XRN1. Also acts as an important regulator of the HIF1A-mediated hypoxic response. Required for HIF1A mRNA stability independent of poly(A) tail length regulation. {ECO:0000255|HAMAP-Rule:MF_03182, ECO:0000269|PubMed:14583602, ECO:0000269|PubMed:16284618, ECO:0000269|PubMed:23398456}.
• Pathway: RNA degradation - Homo sapiens (human);Ectoderm Differentiation;Metabolism of RNA;Deadenylation of mRNA;Deadenylation-dependent mRNA decay (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.616
• rvis_EVS: -0.62
• rvis_percentile_EVS: 17.45

Haploinsufficiency Scores

• pHI: 0.738
• hipred: Y
• hipred_score: 0.515
• ghis: 0.575

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.732

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pan2
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: nuclear-transcribed mRNA poly(A) tail shortening;mRNA processing;positive regulation of cytoplasmic mRNA processing body assembly;RNA phosphodiester bond hydrolysis, exonucleolytic
• Cellular component: P-body;nucleus;cytosol;PAN complex
• Molecular function: 3'-5'-exoribonuclease activity;nucleic acid binding;poly(A)-specific ribonuclease activity;protein binding;metal ion binding