EFS

protein-coding

embryonal Fyn-associated substrate, the group of Cas scaffold proteins

Gene summary

The protein encoded by this gene is a member of the CAS (CRK-associated substrate) family of adaptor proteins which typically serve as scaffolds for the assembly of larger signaling complexes. These complexes form at the cell surface where integrin binding leads to the subsequent phosphorylation of a CAS protein. Additional binding of SRC family kinases leads to CAS hyperphosphorylation and the creation of binding sites for CRK and other proteins that cause actin cytoskeleton reorganization. This gene plays a role in integrin-mediated cell attachment, spreading, and migration and also plays a role in both normal and malignant cellular transformation. This broadly expressed gene has been shown to play a role in neurite outgrowth and its expression in the thymus and lymphocytes is important for T cell maturation and the development of immunological self-tolerance. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2020]

MANE transcript

NM_005864.4

Inheritance

—

ClinVar variants

U:97B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr14:23,356,403-23,365,752

External References & Databases

Ensembl (ENSG00000100842)

Transcript & Mutation Effects

hg38 • Region Span ~9.3 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 EFS variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 91

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005864.4. 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			2 clinvar		1 clinvar	3
missense			93 clinvar	3 clinvar		96
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	97	3	1	101

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005864.4	RefSeq	NP_005855.1	6	MANE Select
ENST00000216733.8	Ensembl	ENSP00000216733.3	6	MANE Select
NM_001277174.2	RefSeq	NP_001264103.1	6	Standard
NM_001385607.1	RefSeq	NP_001372536.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell adhesion
cell migration
intracellular signal transduction
actin filament reorganization

Molecular Function

protein binding
SH3 domain binding
protein domain specific binding

Cellular Component

cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216733
Coding exons: 6
Length: 9351
Individuals with no LoFs: 125695
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125745
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.385	297	316	0.939	0.0000179	3470
Missense (PolyPhen)		114	120.14	0.94891		1312
Synonymous	1.03	129	145	0.891	0.00000873	1315
Loss of Function	0.863	14	17.9	0.780	9.36e-7	211

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00022	0.00020	rare
East Asian	0.00044	0.00044	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0	0.0	absent
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Docking protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion. May serve as an activator of SRC and a downstream effector. Interacts with the SH3 domain of FYN and with CRK, SRC, and YES (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.147

Intolerance Scores

LoFtool: 0.888
RVIS EVS: 1.73
RVIS percentile EVS: 96.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.647

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High