UBASH3B

protein-coding

ubiquitin associated and SH3 domain containing B, the group of Protein phosphatases

Gene summary

This gene encodes a protein that contains a ubiquitin associated domain at the N-terminus, an SH3 domain, and a C-terminal domain with similarities to the catalytic motif of phosphoglycerate mutase. The encoded protein was found to inhibit endocytosis of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor. [provided by RefSeq, Jul 2008]

MANE transcript

NM_032873.5

Inheritance

—

ClinVar variants

U:72B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr11:122,655,722-122,814,473

External References & Databases

Ensembl (ENSG00000154127)

Transcript & Mutation Effects

hg38 • Region Span ~158.8 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 UBASH3B variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 63

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032873.5. 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			4 clinvar	3 clinvar	3 clinvar	10
missense			66 clinvar	2 clinvar	1 clinvar	69
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	72	5	4	81

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032873.5	RefSeq	NP_116262.2	14	MANE Select
ENST00000284273.6	Ensembl	ENSP00000284273.5	14	MANE Select
NM_001363365.2	RefSeq	NP_001350294.1	14	Standard
ENST00001056511.1	Ensembl	ENSP00000726328.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TCR
EGFR1

Biological Process

negative regulation of protein kinase activity
negative regulation of signal transduction
peptidyl-tyrosine dephosphorylation
collagen-activated tyrosine kinase receptor signaling pathway
collagen-activated signaling pathway

Molecular Function

protein tyrosine phosphatase activity
protein binding
phosphatase activity
ubiquitin protein ligase binding
identical protein binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000284273
Coding exons: 14
Length: 158799
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125747
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.99	263	371	0.709	0.0000210	4217
Missense (PolyPhen)		91	152.4	0.5971		1741
Synonymous	1.38	129	151	0.857	0.00000938	1255
Loss of Function	3.47	14	36.6	0.382	0.00000192	403

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000087	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.00023	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. Promotes accumulation of activated target receptors, such as T-cell receptors and EGFR, on the cell surface. Exhibits tyrosine phosphatase activity toward several substrates including EGFR, FAK, SYK, and ZAP70. Down-regulates proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination. {ECO:0000269|PubMed:15159412, ECO:0000269|PubMed:17880946}.;

Recessive Scores

pRec: 0.167

Intolerance Scores

LoFtool: 0.367
RVIS EVS: -0.07
RVIS percentile EVS: 48.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.706

Gene Damage Prediction

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