PJA1

protein-coding

praja ring finger ubiquitin ligase 1, the group of Ring finger proteins

Gene summary

This gene encodes an enzyme that has E2-dependent E3 ubiquitin-protein ligase activity. This enzyme belongs to a class of ubiquitin ligases that include a RING finger motif, and it can interact with the E2 ubiquitin-conjugating enzyme UbcH5B. This gene is located in an area of chromosome X where several X-linked cognitive disability disorders have been associated, and it has also been found as part of a contiguous gene deletion associated with craniofrontonasal syndrome, though a direct link to any disorder has yet to be demonstrated. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

MANE transcript

NM_001032396.4

Inheritance

ClinVar variants

U:75B:15

Top phenotype

PJA1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chrX:69,160,851-69,165,521

External References & Databases

Ensembl (ENSG00000181191)

Transcript & Mutation Effects

hg38 • Region Span ~4.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

X-linked complex neurodevelopmental disorderMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0100148

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PJA1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 63

not providedTotal: 8

PJA1-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001032396.4. 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			4 clinvar	4 clinvar		8
missense			66 clinvar	9 clinvar	2 clinvar	77
nonsense			4 clinvar			4
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	75	13	2	90

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001032396.4	RefSeq	NP_001027568.1	1	MANE Select
ENST00000374571.5	Ensembl	ENSP00000363699.3	1	MANE Select
NM_001382775.1	RefSeq	NP_001369704.1	1	Standard
NM_001382776.1	RefSeq	NP_001369705.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TGF-beta Signaling Pathway
Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation
Class I MHC mediated antigen processing & presentation

Biological Process

protein ubiquitination
protein catabolic process

Molecular Function

protein binding
metal ion binding
ubiquitin protein ligase activity

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361478
Coding exons: 1
Length: 4943
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125746
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.02	226	273	0.827	0.0000223	4256
Missense (PolyPhen)		29	66.949	0.43316		1193
Synonymous	2.02	85	112	0.758	0.00000988	1265
Loss of Function	3.39	2	17.2	0.116	0.00000166	229

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000076	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000024	0.000018	rare
South Asian	0.00011	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has E2-dependent E3 ubiquitin-protein ligase activity. Ubiquitinates MAGED1 antigen leading to its subsequent degradation by proteasome (By similarity). May be involved in protein sorting. {ECO:0000250, ECO:0000269|PubMed:12036302}.;

Recessive Scores

pRec: 0.131

Intolerance Scores

LoFtool: 0.396
RVIS EVS: 0.44
RVIS percentile EVS: 77.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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