CASS4

protein-coding

Cas scaffold protein family member 4, the group of Cas scaffold proteins

Gene summary

Enables protein tyrosine kinase binding activity. Involved in several processes, including positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; positive regulation of protein tyrosine kinase activity; and positive regulation of substrate adhesion-dependent cell spreading. Located in cytoplasm and focal adhesion. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C20orf32

MANE transcript

NM_020356.4

Inheritance

—

ClinVar variants

U:94B:20

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr20:56,412,112-56,460,387

External References & Databases

Ensembl (ENSG00000087589)

Transcript & Mutation Effects

hg38 • Region Span ~48.3 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 CASS4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 104

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020356.4. 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			1 clinvar	2 clinvar	1 clinvar	4
missense			91 clinvar	15 clinvar	2 clinvar	108
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	94	17	3	114

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020356.4	RefSeq	NP_065089.2	6	MANE Select
ENST00000679887.1	Ensembl	ENSP00000506506.1	6	MANE Select
NM_001164114.2	RefSeq	NP_001157586.1	6	Standard
NM_001164115.2	RefSeq	NP_001157587.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell adhesion
cell migration
positive regulation of cell migration
positive regulation of protein tyrosine kinase activity
actin filament reorganization

Molecular Function

protein tyrosine kinase binding

Cellular Component

cytoplasm
cytoskeleton
plasma membrane
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371336
Coding exons: 6
Length: 47229
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125748
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.12	392	459	0.853	0.0000264	5120
Missense (PolyPhen)		73	107.29	0.68038		1295
Synonymous	-0.143	193	190	1.01	0.0000120	1604
Loss of Function	3.70	6	26.5	0.226	0.00000138	317

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.00030	0.00029	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Docking protein that plays a role in tyrosine kinase- based signaling related to cell adhesion and cell spreading. Regulates PTK2/FAK1 activity, focal adhesion integrity, and cell spreading. {ECO:0000269|PubMed:18256281}.;

Recessive Scores

pRec: 0.0839

Intolerance Scores

LoFtool: 0.515
RVIS EVS: -0.1
RVIS percentile EVS: 45.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.314

Gene Damage Prediction

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