SH3GL2

SH3 domain containing GRB2 like 2, endophilin A1, the group of N-BAR domain containing

Basic information

Region (hg38): 9:17579066-17797124

Links

ENSG00000107295 ∙ NCBI:6456 ∙ OMIM:604465 ∙ HGNC:10831 ∙ Uniprot:Q99962 ∙ 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 SH3GL2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SH3GL2 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			19			19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	19	0	1

Variants in SH3GL2

This is a list of pathogenic ClinVar variants found in the SH3GL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-17761447-T-C		not specified	Uncertain significance (Mar 17, 2023)
9-17761452-A-G		not specified	Uncertain significance (May 10, 2024)
9-17761500-C-G		not specified	Uncertain significance (Jan 04, 2022)
9-17786430-C-T			Benign (Aug 05, 2018)
9-17787382-C-T		not specified	Uncertain significance (Jun 14, 2022)
9-17787412-C-T		not specified	Uncertain significance (May 27, 2022)
9-17787427-G-C		not specified	Uncertain significance (Dec 20, 2023)
9-17787457-C-G		not specified	Uncertain significance (Apr 16, 2024)
9-17787464-T-G		not specified	Uncertain significance (Dec 17, 2023)
9-17789477-G-A		not specified	Uncertain significance (Feb 17, 2022)
9-17789490-G-C		not specified	Uncertain significance (Apr 05, 2023)
9-17789536-C-T		not specified	Uncertain significance (Jan 08, 2024)
9-17789545-A-G		not specified	Uncertain significance (Mar 04, 2024)
9-17791303-C-A		not specified	Uncertain significance (May 21, 2024)
9-17791316-C-T		not specified	Uncertain significance (Oct 04, 2022)
9-17793428-G-C		not specified	Uncertain significance (Jul 19, 2022)
9-17793468-T-C		not specified	Uncertain significance (Jul 30, 2023)
9-17793471-C-A		not specified	Uncertain significance (May 31, 2023)
9-17793471-C-T		not specified	Uncertain significance (Sep 01, 2021)
9-17793474-A-T		not specified	Uncertain significance (Dec 27, 2023)
9-17793489-A-G		not specified	Uncertain significance (Jan 11, 2023)
9-17795643-C-G		not specified	Uncertain significance (Aug 15, 2023)
9-17795675-A-G		not specified	Uncertain significance (Oct 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SH3GL2	protein_coding	protein_coding	ENST00000380607	9	218048

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000119	0.991	125706	0	12	125718	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.963	153	190	0.804	0.00000961	2323
Missense in Polyphen		46	74.133	0.62051		925
Synonymous	-2.04	89	67.6	1.32	0.00000353	642
Loss of Function	2.30	10	21.5	0.465	0.00000126	235

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000874	0.0000874
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000795	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Implicated in synaptic vesicle endocytosis. May recruit other proteins to membranes with high curvature. Required for BDNF-dependent dendrite outgrowth. Cooperates with SH3GL2 to mediate BDNF-NTRK2 early endocytic trafficking and signaling from early endosomes. {ECO:0000250|UniProtKB:Q62420}.
• Pathway: Endocytosis - Homo sapiens (human);EGF-EGFR Signaling Pathway;Developmental Biology;Golgi Associated Vesicle Biogenesis;Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;Disease;trans-Golgi Network Vesicle Budding;Signal Transduction;Recycling pathway of L1;Vesicle-mediated transport;Membrane Trafficking;MHC class II antigen presentation;Infectious disease;Immune System;Adaptive Immune System;Retrograde neurotrophin signalling;EGFR downregulation;Signaling by EGFR;Clathrin-mediated endocytosis;Signaling by NTRK1 (TRKA);Signaling by NTRKs;EGFR1;Cargo recognition for clathrin-mediated endocytosis;L1CAM interactions;Axon guidance;Negative regulation of MET activity;Signaling by MET;Signaling by Receptor Tyrosine Kinases;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Internalization of ErbB1;RhoA signaling pathway;InlB-mediated entry of Listeria monocytogenes into host cell;Listeria monocytogenes entry into host cells (Consensus)

Recessive Scores

• pRec: 0.208

Intolerance Scores

• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.36

Haploinsufficiency Scores

• pHI: 0.315
• hipred: Y
• hipred_score: 0.819
• ghis: 0.624

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sh3gl2
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: regulation of receptor internalization;signal transduction;central nervous system development;synaptic vesicle uncoating;antigen processing and presentation of exogenous peptide antigen via MHC class II;neuron projection development;negative regulation of epidermal growth factor receptor signaling pathway;lipid tube assembly;membrane organization;dendrite extension;membrane tubulation;membrane bending;vesicle scission;positive regulation of membrane tubulation;cellular response to brain-derived neurotrophic factor stimulus;regulation of clathrin-dependent endocytosis
• Cellular component: Golgi membrane;early endosome;cytosol;plasma membrane;clathrin-coated endocytic vesicle membrane;synaptic vesicle membrane;neuronal cell body;perinuclear region of cytoplasm;basal dendrite;photoreceptor ribbon synapse;Schaffer collateral - CA1 synapse;hippocampal mossy fiber to CA3 synapse;glutamatergic synapse;presynaptic cytosol
• Molecular function: protein binding;protein C-terminus binding;lipid binding;protein kinase binding;identical protein binding;protein homodimerization activity