Alt. symbols: DAN

Approved name: poly(A)-specific ribonuclease
Alt. names: poly(A)-specific ribonuclease (deadenylation nuclease) | deadenylation nuclease

Location: 16p13.12: 14435700 - 14632728 (-)
Gene type: protein_coding, 39 transcripts.

Scores: LoFtool: | pLI: 0.38718362 | LOEUF: 0.519

HGNC: 8609

NCBI: 5073, RefSeq: NG_042871.1

Ensembl: ENSG00000140694.18

LRG_1286 | Status: public

OMIM: 604212

Expression | ProteinAtlas

to be updated

Bi-allelic mutations in the gene were first associated with dyskeratosis congenita type 6 [MIM:616353]. At least 9 patients from 7 families have been reported carrying bi-allelic mutations (PMID:25893599,26482878,26810774). The reported phenotypes include one patient -who carried a 4-exon deletion (chr16:14658272–14679880) and a missense (R349W) mutation- with severe global developmental delay, mental retardation, delayed speech, hyperreflexia, hypomyelination, bone marrow failure, microcephaly, mid-facial hypoplasia, low-set ears, scoliosis, short stature, thin hair and constipation (PMID:26342108). One patient -who carried a nonsense (R237X) and a 5'UTR (c.-63C>T) variant- with Hoyeraal-Hreidarsson syndrome who initially presented with intrauterine growth retardation, microcephaly, and central nervous system calcifications, but later showed severe developmental delay, cerebellar hypoplasia, esophageal and urethral stenosis, hip avascular necrosis, immunodeficiency, bone marrow failure, progressive skin pigmentation changes, oral leukoplakia, and nail dysplasia leading to anonychia (PMID:26342108). And seven individuals from 5 families diagnosed with dyskeratosis congenita. Mutations in these subjects included a whole gene deletion, missense mutations (N7H, S87L, A383V), splice-altering mutations (c.981+1G>T, c.659+4_659+7delAGTA) and a frameshift (N288KfsX23). However, as with other telomere-related genes, mono-allelic mutations have also been linked to pulmonary fibrosis with or without bone marrow failure [MIM:616371] (PMID:25848748). Stuart et al. (2015) published six families with autosomal dominant pulmonary fibrosis or lung disease -with incomplete penetrance-. Reported mutations included: two splice-site (IVS4-2A>G, IVS16+1G>A), one nonsense (p.Q177X), two frameshift (p.I188fsX7, p.R251EfsX14), and one missense (p.K421R) mutations. identified large monoallelic deletions in PARN in four patients with developmental delay or mental illness. Furthermore, mono-allelic multi-exon deletions in the gene were reported by Dhanraj S. et al (2015) in 3 patients with developmental delay, mental illness and additional phenotypes (PMID:26342108). According to ClinVar, more than 100 mutations have been reported, although just a third are classified as Pathogenic or Likely Pathogenic, whereas over 80 mutations are classified as Variants of Uncertain Significance (VUS). [Load More]