PARN

poly(A)-specific ribonuclease, the group of PARN exonuclease family|Ribosomal biogenesis factors

Basic information

Region (hg38): 16:14435700-14632728

Links

ENSG00000140694 ∙ NCBI:5073 ∙ OMIM:604212 ∙ HGNC:8609 ∙ Uniprot:O95453 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dyskeratosis congenita, autosomal recessive 6 (Definitive), mode of inheritance: AR
• dyskeratosis congenita, autosomal recessive 6 (Moderate), mode of inheritance: AR
• pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (Moderate), mode of inheritance: AD
• dyskeratosis congenita (Supportive), mode of inheritance: AD
• Hoyeraal-Hreidarsson syndrome (Supportive), mode of inheritance: AD
• dyskeratosis congenita, autosomal recessive 6 (Strong), mode of inheritance: AR
• pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pulmonary fibrosis and/or bone marrow failure, telomere-related 4; Dyskeratosis congenita, autosomal recessive 6	AD/AR	Hematologic; Oncologic; Pulmonary	In dyskeratosis congenita, the presentation many not always be classic, and individuals are at high risk for hematologic anomalies (including bone marrow failure) and malignancy, and surveillance and prompt diagnosis and treatment may be beneficial; In Aplastic anemia, surveillance and prompt treatment of aplastic anemia and bone marrow failure may reduce morbidity; For treatment related to pulmonary fibrosis, immunotherapy may be beneficial, though lung transplantation may be indicated in individuals with severe/refractory disease	Dermatologic; Hematologic; Neurologic; Oncologic; Pulmonary	25848748; 25893599; 26342108

ClinVar

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

• Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (15 variants)
• not provided (6 variants)
• Pulmonary fibrosis (5 variants)
• Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (4 variants)
• Dyskeratosis congenita, autosomal recessive 6 (4 variants)
• Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4;Dyskeratosis congenita, autosomal recessive 6 (2 variants)
• Pulmonary fibrosis;Familial Interstitial Pneumonia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PARN 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			4	116		120
missense		1	286	2	2	291
nonsense	15		1			16
start loss						0
frameshift	11	2				13
inframe indel			6			6
splice donor/acceptor (+/-2bp)	2	17	3			22
splice region		1	30	45	6	82
non coding			6	141	23	170
Total	28	20	306	259	25

Highest pathogenic variant AF is 0.0000132

Variants in PARN

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

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

Position	Type	Phenotype	Significance	ClinVar
16-14436721-C-T		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Uncertain significance (Jan 27, 2022)
16-14436722-A-G		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Uncertain significance (May 23, 2023)
16-14436723-T-C		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Likely benign (Jul 03, 2020)
16-14436726-G-T		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Uncertain significance (Apr 18, 2023)
16-14436737-C-T		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Uncertain significance (Sep 26, 2023)
16-14436742-A-C		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Uncertain significance (Sep 04, 2023)
16-14436745-G-C		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Uncertain significance (Jun 20, 2022)
16-14436746-T-C		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Uncertain significance (Jul 25, 2023)
16-14436746-T-G		Inborn genetic diseases	Uncertain significance (Dec 03, 2024)
16-14436750-A-G		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Likely benign (Jan 28, 2020)
16-14436756-G-C		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Uncertain significance (Mar 12, 2022)
16-14436756-G-T		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Uncertain significance (Apr 04, 2022)
16-14436762-C-G		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Likely benign (Sep 27, 2022)
16-14436762-C-T		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 • PARN-related disorder	Likely benign (Apr 21, 2023)
16-14436763-G-A		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 • not specified • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 30, 2023)
16-14436767-T-C		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Uncertain significance (Dec 26, 2023)
16-14436772-C-T		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Uncertain significance (Aug 10, 2023)
16-14436778-G-C		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Likely benign (Jul 17, 2023)
16-14436780-GA-G		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Likely benign (May 07, 2022)
16-14436781-A-G		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Likely benign (Oct 30, 2023)
16-14436788-A-G		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Likely benign (Nov 04, 2021)
16-14436869-G-A		not specified	Benign (Jan 24, 2024)
16-14446868-C-G		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Likely benign (Jul 13, 2023)
16-14446868-C-T		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Likely benign (Aug 29, 2022)
16-14446869-G-A		Dyskeratosis congenita, autosomal recessive 6;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Likely benign (Sep 16, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PARN	protein_coding	protein_coding	ENST00000437198	24	197028

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000373	1.00	124614	0	22	124636	0.0000883

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.794	285	325	0.876	0.0000166	4218
Missense in Polyphen		62	91.965	0.67417		1206
Synonymous	0.573	108	116	0.932	0.00000645	1066
Loss of Function	4.02	14	42.2	0.332	0.00000193	569

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000141	0.000129
Ashkenazi Jewish	0.0000998	0.0000994
East Asian	0.000168	0.000167
Finnish	0.0000465	0.0000464
European (Non-Finnish)	0.0000910	0.0000885
Middle Eastern	0.000168	0.000167
South Asian	0.000171	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 3'-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs and is also used to silence certain maternal mRNAs translationally during oocyte maturation and early embryonic development. Interacts with both the 3'-end poly(A) tail and the 5'-end cap structure during degradation, the interaction with the cap structure being required for an efficient degradation of poly(A) tails. Involved in nonsense-mediated mRNA decay, a critical process of selective degradation of mRNAs that contain premature stop codons. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly via its interaction with KHSRP. Probably mediates the removal of poly(A) tails of AREs mRNAs, which constitutes the first step of destabilization (PubMed:10882133, PubMed:11359775, PubMed:12748283, PubMed:15175153, PubMed:9736620). Also able to recognize and trim poly(A) tails of microRNAs such as MIR21 and H/ACA box snoRNAs (small nucleolar RNAs) leading to microRNAs degradation or snoRNA increased stability (PubMed:25049417, PubMed:22442037). {ECO:0000269|PubMed:10882133, ECO:0000269|PubMed:11359775, ECO:0000269|PubMed:12748283, ECO:0000269|PubMed:15175153, ECO:0000269|PubMed:22442037, ECO:0000269|PubMed:25049417, ECO:0000269|PubMed:9736620}.
• Disease: DISEASE: Dyskeratosis congenita, autosomal recessive, 6 (DKCB6) [MIM:616353]: A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. {ECO:0000269|PubMed:25893599}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pulmonary fibrosis, and/or bone marrow failure, telomere- related, 4 (PFBMFT4) [MIM:616371]: A disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length. {ECO:0000269|PubMed:25848748}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: RNA degradation - Homo sapiens (human);Lung fibrosis;KSRP (KHSRP) binds and destabilizes mRNA;Metabolism of RNA;Regulation of mRNA stability by proteins that bind AU-rich elements;Deadenylation of mRNA;Deadenylation-dependent mRNA decay (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.73

Haploinsufficiency Scores

• pHI: 0.158
• hipred: Y
• hipred_score: 0.653
• ghis: 0.586

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.966

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Parn

Zebrafish Information Network

• Gene name: parn
• Affected structure: myeloid cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;nuclear-transcribed mRNA poly(A) tail shortening;box H/ACA snoRNA 3'-end processing;female gamete generation;RNA modification;miRNA catabolic process;positive regulation of telomere maintenance via telomerase;regulation of mRNA stability;positive regulation of telomerase activity;polyadenylation-dependent snoRNA 3'-end processing;RNA phosphodiester bond hydrolysis, exonucleolytic;telomerase RNA stabilization;ncRNA deadenylation;regulation of telomerase RNA localization to Cajal body
• Cellular component: nucleus;nucleolus;cytoplasm;cytosol
• Molecular function: 3'-5'-exoribonuclease activity;RNA binding;mRNA 3'-UTR binding;nuclease activity;poly(A)-specific ribonuclease activity;protein binding;protein kinase binding;cation binding;metal ion binding;telomerase RNA binding