TAX1BP3

Chr 17

Tax1 binding protein 3

Also known as: TIP-1, TIP1

NCBI Gene: 30851 ENSG00000213977 UniProt: O14907 OMIM: 616484

The protein contains a PDZ domain that mediates protein-protein interactions, regulating cell signaling pathways including Wnt/beta-catenin signaling and modulating potassium channel localization. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and progressive microcephaly. The gene shows tolerance to loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a small, highly conserved protein with a single PDZ domain. PDZ (PSD-95/Discs large/ZO-1 homologous) domains promote protein-protein interactions that affect cell signaling, adhesion, protein scaffolding, and receptor and ion transporter functions. The encoded protein interacts with a large number of target proteins that play roles in signaling pathways; for example, it interacts with Rho A and glutaminase L and also acts as a negative regulator of the Wnt/beta-catenin signaling pathway. This protein was first identified as binding to the T-cell leukaemia virus (HTLV1) Tax oncoprotein. Overexpression of this gene has been implicated in altered cancer cell adhesion, migration and metastasis. The encoded protein also modulates the localization and density of inwardly rectifying potassium channel 2.3 (Kir2.3). To date, this protein has been shown to play a role in cell proliferation, development, stress response, and polarization. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2017]

OMIM ResearchGenerating clinical summary…

LOEUF 1.49

Clinical Summary— TAX1BP3

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 36 VUS of 50 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.49LOEUF

pLI 0.005

Z-score 0.76

OE 0.66 (0.33–1.49)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.90Z-score

OE missense 0.72 (0.59–0.90)

60 obs / 83.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.33–1.49)

0≤0.351.4

Missense OE?0.72 (0.59–0.90)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 4 / 6.0Missense obs/exp: 60 / 83.0Syn Z: 0.78

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS36

Likely Benign3

Benign9

Conflicting1

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	1	0	1
VUS	1	27	8	0	36
Likely Benign	0	0	2	1	3
Benign	0	1	5	3	9
Conflicting	—				1
Total	1	28	16	4	50

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

34 pathogenic / likely-pathogenic (of 61) ClinVar copy-number / structural variants overlap TAX1BP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →