UBASH3A

protein-coding

ubiquitin associated and SH3 domain containing A

Gene summary

This gene encodes one of two family members belonging to the T-cell ubiquitin ligand (TULA) family. Both family members can negatively regulate T-cell signaling. This family member can facilitate growth factor withdrawal-induced apoptosis in T cells, which may occur via its interaction with AIF, an apoptosis-inducing factor. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

MANE transcript

NM_018961.4

Inheritance

—

ClinVar variants

U:121B:19

Top phenotype

UBASH3A-related disorder

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr21:42,403,447-42,447,684

External References & Databases

Ensembl (ENSG00000160185)

Transcript & Mutation Effects

hg38 • Region Span ~44.2 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 UBASH3A variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 130

not providedTotal: 8

UBASH3A-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018961.4. 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	3 clinvar	5 clinvar	9
missense			119 clinvar	10 clinvar	1 clinvar	130
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	121	13	6	140

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018961.4	RefSeq	NP_061834.1	15	MANE Select
ENST00000319294.11	Ensembl	ENSP00000317327.6	15	MANE Select
NM_001001895.3	RefSeq	NP_001001895.1	14	Standard
NM_001243467.2	RefSeq	NP_001230396.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of cytokine production
negative regulation of signal transduction
dephosphorylation
negative regulation of T cell receptor signaling pathway

Molecular Function

protein binding
phosphatase activity

Cellular Component

nucleoplasm
Golgi apparatus
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000319294
Coding exons: 15
Length: 43784
Individuals with no LoFs: 125679
Homozygous LoFs: 0
Heterozygous LoFs: 69
Defined: 125748
p: 0.000274

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.344	375	394	0.951	0.0000244	4300
Missense (PolyPhen)		118	137.01	0.86123		1496
Synonymous	0.0163	173	173	0.998	0.0000127	1282
Loss of Function	1.93	21	33.0	0.637	0.00000170	370

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00035	0.00034	rare
South Asian	0.00036	0.00036	rare
Other	0.00033	0.00033	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, EGFR and PDGFRB, on the cell surface. Exhibits negligigle protein tyrosine phosphatase activity at neutral pH. May act as a dominant-negative regulator of UBASH3B-dependent dephosphorylation. May inhibit dynamin-dependent endocytic pathways by functionally sequestering dynamin via its SH3 domain. {ECO:0000269|PubMed:15159412, ECO:0000269|PubMed:17382318, ECO:0000269|PubMed:18189269}.;

Recessive Scores

pRec: 0.145

Intolerance Scores

LoFtool: 0.804
RVIS EVS: -0.88
RVIS percentile EVS: 10.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.543

Gene Damage Prediction

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