PNLDC1

protein-coding

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

Gene summary

Enables poly(A)-specific ribonuclease activity. Involved in nuclear-transcribed mRNA poly(A) tail shortening; piRNA processing; and spermatogenesis. Located in endoplasmic reticulum. Implicated in spermatogenic failure 57. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001271862.2

Inheritance

ClinVar variants

P:11U:57B:9

Top phenotype

Spermatogenic failure 57

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr6:159,800,249-159,820,704

External References & Databases

Ensembl (ENSG00000146453)

Transcript & Mutation Effects

hg38 • Region Span ~20.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 57LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030439

Submitter: Labcorp Genetics (formerly Invitae)

spermatogenic failure 57STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030439

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spermatogenic failure 57AR

Manifestation: Endocrine; Genitourinary

Intervention: General

Rationale: 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

Refs: 34347949

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PNLDC1 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 59

Spermatogenic failure 57Total: 10

not providedTotal: 4

Male infertility with azoospermia or oligozoospermia due to single gene mutationTotal: 3

Non-obstructive azoospermiaTotal: 3

Male infertilityTotal: 2

PNLDC1-related conditionTotal: 1

OligospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001271862.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	3 clinvar		4
missense	2 clinvar	2 clinvar	55 clinvar	6 clinvar		65
nonsense	1 clinvar					1
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)	2 clinvar	3 clinvar				5
Total	6	5	57	9	0	77

Highest pathogenic variant AF is 0.000028500795

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001271862.2	RefSeq	NP_001258791.1	19	MANE Select
ENST00000392167.4	Ensembl	ENSP00000376007.3	19	MANE Select
NM_173516.3	RefSeq	NP_775787.1	18	Standard
ENST00000275275.9	Ensembl	ENSP00000275275.6	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA degradation - Homo sapiens (human)

Biological Process

nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
nuclear-transcribed mRNA poly(A) tail shortening
blastocyst formation
RNA phosphodiester bond hydrolysis, exonucleolytic

Molecular Function

3'-5'-exoribonuclease activity
RNA binding
poly(A)-specific ribonuclease activity
metal ion binding

Cellular Component

cytoplasm
endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000610273
Coding exons: 18
Length: 20439
Individuals with no LoFs: 125647
Homozygous LoFs: 0
Heterozygous LoFs: 101
Defined: 125748
p: 0.000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.797	261	300	0.870	0.0000171	3446
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00061	0.00061	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.00042	0.00042	rare
European (Non-Finnish)	0.00043	0.00040	rare
South Asian	0.00042	0.00042	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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}.;

Intolerance Scores

LoFtool: 0.328
RVIS EVS: -1
RVIS percentile EVS: 8.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0903

Gene Damage Prediction

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