SH3RF3

protein-coding

SH3 domain containing ring finger 3, the group of Ring finger proteins

Gene summary

Enables ubiquitin protein ligase activity. Involved in positive regulation of JNK cascade and protein autoubiquitination. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

SH3MD4

MANE transcript

NM_001099289.3

Inheritance

—

ClinVar variants

U:141B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr2:109,129,205-109,504,634

External References & Databases

Ensembl (ENSG00000172985)

Transcript & Mutation Effects

hg38 • Region Span ~375.4 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 SH3RF3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 143

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001099289.3. 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			5 clinvar	2 clinvar		7
missense			133 clinvar	10 clinvar		143
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	141	12	0	153

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001099289.3	RefSeq	NP_001092759.1	10	MANE Select
ENST00000309415.8	Ensembl	ENSP00000309186.6	10	MANE Select
ENST00001111616.1	Ensembl	ENSP00000781421.1	8	Standard
ENST00001144963.1	Ensembl	ENSP00000806039.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of JNK cascade
protein autoubiquitination

Molecular Function

protein binding
metal ion binding
ubiquitin protein ligase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000309415
Coding exons: 10
Length: 516404
Individuals with no LoFs: 125066
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125084
p: 0.0000720

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.53	394	489	0.805	0.0000307	5539
Missense (PolyPhen)		102	173.61	0.58752		1923
Synonymous	-1.21	247	224	1.10	0.0000156	1939
Loss of Function	3.43	8	27.4	0.292	0.00000126	338

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000063	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.00014	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has E3 ubiquitin-protein ligase activity. {ECO:0000269|PubMed:20696164}.;

Essentials

Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0461

Gene Damage Prediction

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