PDZRN3

protein-coding

PDZ domain containing ring finger 3, the group of Zinc fingers TRAF-type|PDZ domain containing|Ring finger proteins

Gene summary

This gene encodes a member of the LNX (Ligand of Numb Protein-X) family of RING-type ubiquitin E3 ligases. This protein may function in vascular morphogenesis and the differentiation of adipocytes, osteoblasts and myoblasts. This protein may be targeted for degradation by the human papilloma virus E6 protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

MANE transcript

NM_015009.3

Inheritance

—

ClinVar variants

P:2U:197B:10

Top phenotype

Short stature

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr3:73,382,431-73,624,941

External References & Databases

Ensembl (ENSG00000121440)

Transcript & Mutation Effects

hg38 • Region Span ~242.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PDZRN3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 193

not providedTotal: 9

Short statureTotal: 2

Childhood-onset schizophreniaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015009.3. 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	2 clinvar	6
missense		2 clinvar	193 clinvar	3 clinvar	1 clinvar	199
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar		1 clinvar	2
Total	0	2	197	6	4	209

Highest pathogenic variant AF is 0.000018091927

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015009.3	RefSeq	NP_055824.1	10	MANE Select
ENST00000263666.9	Ensembl	ENSP00000263666.4	10	MANE Select
NM_001303139.2	RefSeq	NP_001290068.1	8	Standard
NM_001303140.2	RefSeq	NP_001290069.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

neuromuscular junction development
protein ubiquitination

Molecular Function

ubiquitin-protein transferase activity
zinc ion binding
ubiquitin protein ligase activity

Cellular Component

nucleus
nucleoplasm
cytosol
cell junction
neuromuscular junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263666
Coding exons: 10
Length: 242508
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.00506	623	623	1.00	0.0000410	6941
Missense (PolyPhen)		188	219.42	0.85679		2365
Synonymous	-2.02	322	279	1.15	0.0000219	2050
Loss of Function	4.68	5	34.7	0.144	0.00000157	443

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase. Plays an important role in regulating the surface level of MUSK on myotubes. Mediates the ubiquitination of MUSK, promoting its endocytosis and lysosomal degradation. Might contribute to terminal myogenic differentiation. {ECO:0000250|UniProtKB:Q69ZS0}.;

Recessive Scores

pRec: 0.133

Intolerance Scores

LoFtool: 0.280
RVIS EVS: -0.99
RVIS percentile EVS: 8.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.741

Gene Damage Prediction

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