PNLDC1

PARN like ribonuclease domain containing exonuclease 1, the group of PARN exonuclease family

Basic information

Region (hg38): 6:159800249-159820704

Links

ENSG00000146453 ∙ NCBI:154197 ∙ OMIM:619529 ∙ HGNC:21185 ∙ Uniprot:Q8NA58 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 57 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 57	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Endocrine; Genitourinary	34347949

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PNLDC1 gene.

• Spermatogenic failure 57 (3 variants)
• Male infertility with azoospermia or oligozoospermia due to single gene mutation (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PNLDC1 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	1	2	26	4		33
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region				1		1
non coding						0
Total	3	3	26	5	0

Highest pathogenic variant AF is 0.0000197

Variants in PNLDC1

This is a list of pathogenic ClinVar variants found in the PNLDC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-159800321-C-G			Uncertain significance (Apr 01, 2024)
6-159800739-C-G			Likely benign (Dec 01, 2022)
6-159800816-C-T		not specified	Uncertain significance (Aug 15, 2023)
6-159801113-T-TC		Spermatogenic failure 57	Pathogenic (May 12, 2022)
6-159801150-C-G		Spermatogenic failure 57	Pathogenic (May 12, 2022)
6-159803292-T-C		not specified	Uncertain significance (Mar 17, 2023)
6-159803971-A-G		not specified	Uncertain significance (Mar 07, 2024)
6-159803999-C-T		Male infertility with azoospermia or oligozoospermia due to single gene mutation • Spermatogenic failure 57	Pathogenic (Jul 22, 2021)
6-159804006-C-T		not specified	Uncertain significance (Aug 14, 2023)
6-159804561-G-A		not specified	Uncertain significance (Oct 07, 2024)
6-159804577-A-G		not specified	Uncertain significance (Feb 15, 2023)
6-159804578-T-G		not specified	Uncertain significance (Aug 08, 2023)
6-159804605-C-G		not specified	Uncertain significance (Oct 14, 2023)
6-159804628-G-T		not specified	Uncertain significance (Dec 30, 2024)
6-159805983-C-T		not specified	Likely benign (Jan 19, 2024)
6-159805988-C-T		not specified	Likely benign (Jan 16, 2025)
6-159806020-G-A		not specified	Likely benign (Feb 05, 2024)
6-159806038-G-C		not specified	Uncertain significance (May 04, 2023)
6-159806044-G-A		not specified	Uncertain significance (Jun 05, 2023)
6-159809013-A-T		Male infertility with azoospermia or oligozoospermia due to single gene mutation • Spermatogenic failure 57	Pathogenic (Jul 22, 2021)
6-159809015-G-C		not specified	Uncertain significance (Jul 15, 2021)
6-159809076-G-A		not specified	Uncertain significance (Feb 28, 2023)
6-159809118-G-A		Non-obstructive azoospermia • Oligospermia	Likely pathogenic (Jan 01, 2022)
6-159809150-G-A		not specified	Uncertain significance (Jan 16, 2024)
6-159810032-G-T		Male infertility	Uncertain significance (Feb 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PNLDC1	protein_coding	protein_coding	ENST00000610273	18	20439

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.12e-14	0.588	125647	0	101	125748	0.000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.797	261	300	0.870	0.0000171	3446
Missense in Polyphen		69	99.001	0.69696		1215
Synonymous	-1.15	138	122	1.13	0.00000807	955
Loss of Function	1.63	27	37.8	0.713	0.00000214	388

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000853	0.000853
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.000416	0.000416
European (Non-Finnish)	0.000431	0.000396
Middle Eastern	0.000381	0.000381
South Asian	0.000425	0.000425
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 3'-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails (PubMed:27515512). 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 (PubMed:27515512). May act as a regulator of multipotency in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:B2RXZ1, ECO:0000269|PubMed:27515512}.
• Pathway: RNA degradation - Homo sapiens (human) (Consensus)

Intolerance Scores

• loftool: 0.328
• rvis_EVS: -1
• rvis_percentile_EVS: 8.47

Haploinsufficiency Scores

• pHI: 0.107
• hipred: N
• hipred_score: 0.354
• ghis: 0.461

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0903

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pnldc1
• Phenotype: reproductive system phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;nuclear-transcribed mRNA poly(A) tail shortening;blastocyst formation;RNA phosphodiester bond hydrolysis, exonucleolytic
• Cellular component: cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane
• Molecular function: 3'-5'-exoribonuclease activity;RNA binding;poly(A)-specific ribonuclease activity;metal ion binding