SH3RF2

protein-coding

SH3 domain containing ring finger 2, the group of Protein phosphatase 1 regulatory subunits|Ring finger proteins

Gene summary

Enables protein phosphatase 1 binding activity and ubiquitin protein ligase activity. Involved in several processes, including positive regulation of JNK cascade; protein autoubiquitination; and regulation of protein metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

PPP1R39

MANE transcript

NM_152550.4

Inheritance

—

ClinVar variants

U:139B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr5:145,936,578-146,081,791

External References & Databases

Ensembl (ENSG00000156463)

Transcript & Mutation Effects

hg38 • Region Span ~145.2 kb

Loading mutation effect viewer...

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 SH3RF2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 136

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152550.4. 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			2 clinvar			2
missense			130 clinvar	6 clinvar		136
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	139	6	0	145

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152550.4	RefSeq	NP_689763.4	9	MANE Select
ENST00000359120.9	Ensembl	ENSP00000352028.4	9	MANE Select
ENST00000511217.1	Ensembl	ENSP00000424497.1	9	Standard
ENST00000511217.2	Ensembl	ENSP00000424497.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of phosphatase activity
positive regulation of cell migration
negative regulation of protein ubiquitination
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
negative regulation of phosphoprotein phosphatase activity

Molecular Function

protein phosphatase inhibitor activity
protein binding
protein phosphatase 1 binding
phosphatase binding
metal ion binding

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000511217
Coding exons: 9
Length: 145213
Individuals with no LoFs: 125614
Homozygous LoFs: 0
Heterozygous LoFs: 134
Defined: 125748
p: 0.000533

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.124	448	441	1.02	0.0000268	4704
Missense (PolyPhen)		145	135.89	1.067		1494
Synonymous	-0.997	209	191	1.09	0.0000124	1577
Loss of Function	0.941	23	28.4	0.810	0.00000163	311

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00062	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.00065	0.00065	rare
South Asian	0.00072	0.00072	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has E3 ubiquitin-protein ligase activity (PubMed:24130170). Acts as an anti-apoptotic regulator of the JNK pathway by ubiquitinating and promoting the degradation of SH3RF1, a scaffold protein that is required for pro-apoptotic JNK activation (PubMed:22128169). Facilitates TNF-alpha-mediated recruitment of adapter proteins TRADD and RIPK1 to TNFRSF1A and regulates PAK4 protein stability via inhibition of its ubiquitin- mediated proteasomal degradation (PubMed:24130170). Inhibits PPP1CA phosphatase activity (PubMed:19945436, PubMed:19389623). {ECO:0000269|PubMed:19389623, ECO:0000269|PubMed:19945436, ECO:0000269|PubMed:22128169, ECO:0000269|PubMed:24130170}.;

Recessive Scores

pRec: 0.0978

Intolerance Scores

LoFtool: 0.554
RVIS EVS: -0.15
RVIS percentile EVS: 42.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.513

Gene Damage Prediction

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