SH3KBP1

SH3 domain containing kinase binding protein 1

Basic information

Region (hg38): X:19533976-19887600

Links

ENSG00000147010 ∙ NCBI:30011 ∙ OMIM:300374 ∙ HGNC:13867 ∙ Uniprot:Q96B97 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 61 (Limited), mode of inheritance: Unknown
• immunodeficiency 61 (Limited), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 61	XL	Allergy/Immunology/Infectious	The condition has been described as including early-onset, severe infections, and awareness may allow preventative measures and early and aggressive treatment of infections	Allergy/Immunology/Infectious; Neurologic	29636373

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SH3KBP1 gene.

• not provided (194 variants)
• Inborn genetic diseases (13 variants)
• Immunodeficiency 61 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SH3KBP1 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				70	12	82
missense			71	4	3	78
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	7	1	11
non coding				19	5	24
Total	0	0	72	93	20

Variants in SH3KBP1

This is a list of pathogenic ClinVar variants found in the SH3KBP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-19536420-T-C			Likely benign (Mar 12, 2022)
X-19536443-T-G			Uncertain significance (May 05, 2023)
X-19536446-C-T		not specified	Uncertain significance (Apr 26, 2023)
X-19536447-G-A			Likely benign (Nov 28, 2023)
X-19536458-T-C			Uncertain significance (Dec 18, 2023)
X-19536474-T-C			Likely benign (Jul 10, 2023)
X-19537707-A-G			Likely benign (Sep 20, 2023)
X-19537708-G-C			Likely benign (Oct 03, 2023)
X-19537712-C-T			Uncertain significance (Jun 27, 2023)
X-19537724-C-T			Benign (Jan 29, 2024)
X-19537725-G-A			Uncertain significance (Sep 30, 2023)
X-19537728-G-A		not specified	Uncertain significance (Jan 02, 2024)
X-19537729-C-G			Likely benign (Apr 15, 2023)
X-19537729-C-T			Likely benign (Apr 14, 2023)
X-19537744-T-G			Uncertain significance (Feb 09, 2023)
X-19537746-C-T			Uncertain significance (Sep 08, 2022)
X-19537753-C-T			Likely benign (Oct 13, 2023)
X-19537761-A-G			Likely benign (Aug 19, 2022)
X-19537778-C-T			Uncertain significance (May 22, 2023)
X-19541910-T-A			Likely benign (Aug 04, 2023)
X-19541911-C-T			Benign (Jan 29, 2024)
X-19541912-C-T			Likely benign (Dec 16, 2023)
X-19541935-C-T			Uncertain significance (Nov 25, 2023)
X-19541936-C-T			Likely benign (Dec 11, 2023)
X-19541941-T-A		not specified	Uncertain significance (Dec 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SH3KBP1	protein_coding	protein_coding	ENST00000397821	18	353627

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00101	125323	0	1	125324	0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.05	178	273	0.651	0.0000225	4329
Missense in Polyphen		19	47.477	0.40019		759
Synonymous	-1.25	138	121	1.14	0.0000114	1305
Loss of Function	4.39	1	24.4	0.0410	0.00000178	454

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000365	0.0000365
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. {ECO:0000250, ECO:0000269|PubMed:11894095, ECO:0000269|PubMed:11894096, ECO:0000269|PubMed:12177062, ECO:0000269|PubMed:12734385, ECO:0000269|PubMed:12771190, ECO:0000269|PubMed:15090612, ECO:0000269|PubMed:15707590, ECO:0000269|PubMed:16177060, ECO:0000269|PubMed:16256071, ECO:0000269|PubMed:21834987}.
• Pathway: Endocytosis - Homo sapiens (human);EGF-EGFR Signaling Pathway;Developmental Biology;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Disease;Signal Transduction;Vesicle-mediated transport;sprouty regulation of tyrosine kinase signals;cbl mediated ligand-induced downregulation of egf receptors pathway;Membrane Trafficking;Signaling by the B Cell Receptor (BCR);Infectious disease;Immune System;Adaptive Immune System;KitReceptor;EGFR downregulation;Signaling by EGFR;Clathrin-mediated endocytosis;EGFR1;Cargo recognition for clathrin-mediated endocytosis;Axon guidance;Reelin signalling pathway;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;InlB-mediated entry of Listeria monocytogenes into host cell;Listeria monocytogenes entry into host cells (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.309
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.64

Haploinsufficiency Scores

• pHI: 0.829
• hipred: Y
• hipred_score: 0.752
• ghis: 0.555

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.704

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sh3kbp1
• Phenotype: homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; hematopoietic system 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); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: sh3kbp1
• Affected structure: blood cell
• Phenotype tag: abnormal
• Phenotype quality: accumulation

Gene ontology

• Biological process: endocytosis;apoptotic process;cytoskeleton organization;cell-cell signaling;axon guidance;regulation of cell shape;cell migration;negative regulation of epidermal growth factor receptor signaling pathway;membrane organization
• Cellular component: cytoplasm;cytosol;cytoskeleton;plasma membrane;cell-cell junction;focal adhesion;endocytic vesicle;cytoplasmic vesicle membrane;neuron projection;synapse
• Molecular function: protein binding;SH3 domain binding