SH3RF1

SH3 domain containing ring finger 1, the group of Ring finger proteins

Basic information

Region (hg38): 4:169094258-169270956

Previous symbols: [ "SH3MD2" ]

Links

ENSG00000154447 ∙ NCBI:57630 ∙ OMIM:618642 ∙ HGNC:17650 ∙ Uniprot:Q7Z6J0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SH3RF1 gene.

• Inborn genetic diseases (30 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SH3RF1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			29	1	1	31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	0	0	30	1	2

Variants in SH3RF1

This is a list of pathogenic ClinVar variants found in the SH3RF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-169106848-T-C		not specified	Uncertain significance (Feb 27, 2023)
4-169106850-T-C		not specified	Uncertain significance (May 09, 2023)
4-169106857-C-T		not specified	Uncertain significance (Dec 17, 2023)
4-169106894-G-A			Benign (Aug 15, 2018)
4-169106898-C-G		not specified	Uncertain significance (Dec 06, 2022)
4-169106919-G-C		not specified	Uncertain significance (Oct 26, 2022)
4-169107000-G-A		not specified	Uncertain significance (Aug 02, 2023)
4-169107103-T-A		not specified	Uncertain significance (Aug 16, 2021)
4-169107139-G-C		not specified	Uncertain significance (Jul 26, 2022)
4-169116306-C-T		not specified	Uncertain significance (Jan 23, 2024)
4-169116391-A-G		not specified	Uncertain significance (Feb 06, 2023)
4-169116445-G-A		not specified	Uncertain significance (Aug 30, 2022)
4-169116507-G-A			Benign (Apr 04, 2018)
4-169116534-T-C		not specified	Uncertain significance (Feb 10, 2023)
4-169116562-G-A		not specified	Uncertain significance (Jun 06, 2023)
4-169116565-C-T		not specified	Uncertain significance (Mar 23, 2022)
4-169117540-C-T		not specified	Uncertain significance (Nov 15, 2021)
4-169117541-G-A		not specified	Uncertain significance (Jan 03, 2024)
4-169117567-G-A		not specified	Uncertain significance (Dec 08, 2021)
4-169117723-C-T		not specified	Uncertain significance (Jun 26, 2023)
4-169117736-C-T		not specified	Uncertain significance (Oct 20, 2021)
4-169120912-A-G		not specified	Uncertain significance (May 31, 2023)
4-169122155-T-C		not specified	Uncertain significance (Sep 25, 2023)
4-169122161-T-A		not specified	Uncertain significance (Jun 03, 2022)
4-169122188-C-T		not specified	Uncertain significance (Feb 12, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SH3RF1	protein_coding	protein_coding	ENST00000284637	11	176850

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0108	0.989	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.51	417	513	0.812	0.0000284	5700
Missense in Polyphen		140	217.15	0.64471		2478
Synonymous	1.30	183	207	0.885	0.0000124	1930
Loss of Function	3.77	10	33.6	0.298	0.00000189	381

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000620	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.0000716	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination (PubMed:15659549, PubMed:20696164). Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-independent endocytosis (PubMed:19710010). Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4(+) and CD8(+) T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4(+) T-cells and the activation of MAPK8/JNK1 in CD8(+) T-cells. Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (By similarity). {ECO:0000250|UniProtKB:Q69ZI1, ECO:0000269|PubMed:15659549, ECO:0000269|PubMed:19710010, ECO:0000269|PubMed:20696164}.
• Pathway: EGF-Ncore;G13 Signaling Pathway;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.138

Intolerance Scores

• loftool: 0.303
• rvis_EVS: -0.57
• rvis_percentile_EVS: 18.96

Haploinsufficiency Scores

• pHI: 0.666
• hipred: Y
• hipred_score: 0.670
• ghis: 0.538

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.896

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sh3rf1

Gene ontology

• Biological process: neuron migration;apoptotic process;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;regulation of CD4-positive, alpha-beta T cell differentiation;positive regulation of JNK cascade;protein autoubiquitination;regulation of CD8-positive, alpha-beta T cell proliferation;negative regulation of extrinsic apoptotic signaling pathway
• Cellular component: Golgi apparatus;cytosol;lamellipodium;perinuclear region of cytoplasm
• Molecular function: MAP-kinase scaffold activity;protein binding;metal ion binding;ubiquitin protein ligase activity