CD2AP

CD2 associated protein

Basic information

Region (hg38): 6:47477789-47627263

Links

ENSG00000198087 ∙ NCBI:23607 ∙ OMIM:604241 ∙ HGNC:14258 ∙ Uniprot:Q9Y5K6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• focal segmental glomerulosclerosis 3, susceptibility to (Limited), mode of inheritance: AR
• familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
• focal segmental glomerulosclerosis 3, susceptibility to (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Focal segmental glomerulosclerosis 3	AR	Renal	The condition can involve renal failure, and early diagnosis may enable management considerations; Renal transplant has been described	Renal	17713465

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD2AP gene.

• Focal segmental glomerulosclerosis 3, susceptibility to (3 variants)
• Focal segmental glomerulosclerosis 3 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD2AP 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			3	31	1	35
missense			100	12		112
nonsense	1	1	1			3
start loss						0
frameshift	2	2	2			6
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)	1	1				2
splice region			5	13		18
non coding			66	44	57	167
Total	4	4	174	88	58

Highest pathogenic variant AF is 0.0000264

Variants in CD2AP

This is a list of pathogenic ClinVar variants found in the CD2AP region.

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

Position	Type	Phenotype	Significance	ClinVar
6-47477804-C-A		Focal segmental glomerulosclerosis 3, susceptibility to	Benign/Likely benign (Jan 16, 2020)
6-47477804-C-G		Focal segmental glomerulosclerosis 3, susceptibility to	Benign (Nov 11, 2018)
6-47477807-C-T		Focal segmental glomerulosclerosis 3, susceptibility to	Uncertain significance (Jan 12, 2018)
6-47477916-C-T		Focal segmental glomerulosclerosis 3, susceptibility to	Uncertain significance (Jan 12, 2018)
6-47477921-G-C		Focal segmental glomerulosclerosis 3, susceptibility to	Uncertain significance (Jan 13, 2018)
6-47477948-G-C		Focal segmental glomerulosclerosis 3, susceptibility to	Benign (Jan 13, 2018)
6-47477978-G-A		Focal segmental glomerulosclerosis 3, susceptibility to	Benign (Jan 13, 2018)
6-47478048-C-T		Focal segmental glomerulosclerosis 3, susceptibility to	Uncertain significance (Jan 13, 2018)
6-47478053-A-C		Focal segmental glomerulosclerosis 3, susceptibility to	Benign (Nov 10, 2018)
6-47478054-G-A		Focal segmental glomerulosclerosis 3, susceptibility to	Uncertain significance (Jan 13, 2018)
6-47478075-TAGG-T		Focal segmental glomerulosclerosis	Likely benign (Jun 14, 2016)
6-47478079-A-G		Focal segmental glomerulosclerosis 3, susceptibility to	Uncertain significance (Apr 27, 2017)
6-47478115-C-G		Focal segmental glomerulosclerosis 3, susceptibility to	Uncertain significance (Jan 13, 2018)
6-47478176-C-A		Focal segmental glomerulosclerosis 3, susceptibility to	Uncertain significance (Jan 13, 2018)
6-47478191-T-A		Focal segmental glomerulosclerosis 3, susceptibility to • not specified	Benign (Jul 15, 2024)
6-47478190-C-CAGG		Focal segmental glomerulosclerosis	Likely benign (Jun 14, 2016)
6-47478236-G-GC		Focal segmental glomerulosclerosis	Uncertain significance (Jun 14, 2016)
6-47478251-AAG-A			Likely benign (Aug 09, 2022)
6-47478257-C-G			Likely benign (Nov 27, 2020)
6-47478264-G-A		not specified	Benign/Likely benign (Jan 02, 2024)
6-47478510-T-G			Benign (Nov 10, 2018)
6-47503260-G-A		Focal segmental glomerulosclerosis 3, susceptibility to	Likely benign (Jun 27, 2023)
6-47503280-T-G			Uncertain significance (May 06, 2023)
6-47503284-C-G		CD2AP-related disorder	Uncertain significance (Oct 11, 2023)
6-47503298-A-G		Inborn genetic diseases	Uncertain significance (Oct 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD2AP	protein_coding	protein_coding	ENST00000359314	18	149475

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.230	0.770	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00215	323	323	1.00	0.0000155	4158
Missense in Polyphen		63	82.35	0.76502		1105
Synonymous	-0.607	122	114	1.07	0.00000551	1212
Loss of Function	4.36	9	38.0	0.237	0.00000202	483

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000446	0.000445
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000167	0.000167
Middle Eastern	0.000109	0.000109
South Asian	0.000196	0.000196
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton (PubMed:10339567). In collaboration with CBLC, modulates the rate of RET turnover and may act as regulatory checkpoint that limits the potency of GDNF on neuronal survival. Controls CBLC function, converting it from an inhibitor to a promoter of RET degradation (By similarity). May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell (By similarity). May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis (PubMed:15800069). Plays a role in epithelial cell junctions formation (PubMed:22891260). {ECO:0000250|UniProtKB:F1LRS8, ECO:0000250|UniProtKB:Q9JLQ0, ECO:0000269|PubMed:10339567, ECO:0000269|PubMed:15800069, ECO:0000269|PubMed:22891260}.
• Disease: DISEASE: Focal segmental glomerulosclerosis 3 (FSGS3) [MIM:607832]: A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. {ECO:0000269|PubMed:12764198}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Bacterial invasion of epithelial cells - Homo sapiens (human);Primary Focal Segmental Glomerulosclerosis FSGS;TCR;Nephrin family interactions;Cell-Cell communication;Nephrin/Neph1 signaling in the kidney podocyte;VEGFR1 specific signals (Consensus)

Recessive Scores

• pRec: 0.379

Intolerance Scores

• loftool: 0.696
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.43

Haploinsufficiency Scores

• pHI: 0.695
• hipred: Y
• hipred_score: 0.708
• ghis: 0.656

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.894

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cd2ap
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; immune system phenotype; renal/urinary system 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: cd2ap
• Affected structure: podocyte
• Phenotype tag: abnormal
• Phenotype quality: structure

Gene ontology

• Biological process: substrate-dependent cell migration, cell extension;actin filament organization;cell cycle;signal transduction;vesicle organization;negative regulation of transforming growth factor beta1 production;proteasome-mediated ubiquitin-dependent protein catabolic process;regulation of receptor-mediated endocytosis;negative regulation of small GTPase mediated signal transduction;cell division;protein-containing complex assembly;cell-cell adhesion;positive regulation of protein localization to nucleus;regulation of actin cytoskeleton reorganization
• Cellular component: ruffle;cytoplasm;plasma membrane;cell-cell junction;actin cytoskeleton;endocytic vesicle;filamentous actin;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: vascular endothelial growth factor receptor binding;structural constituent of cytoskeleton;protein binding;beta-catenin binding;protein C-terminus binding;SH3 domain binding;protein-containing complex binding;cadherin binding