TBL2

Chr 7

transducin beta like 2

Also known as: WBSCR13, WS-betaTRP

NCBI Gene: 26608 ENSG00000106638 UniProt: Q9Y4P3

The protein is a member of the beta-transducin family involved in intracellular signaling pathways. TBL2 is deleted as part of the multigene deletion at 7q11.23 that causes Williams-Beuren syndrome, a developmental disorder with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants in the general population.

ResearchSummary from RefSeq

This gene encodes a member of the beta-transducin protein family. Most proteins of the beta-transducin family are involved in regulatory functions. This protein is possibly involved in some intracellular signaling pathway. This gene is deleted in Williams-Beuren syndrome, a developmental disorder caused by deletion of multiple genes at 7q11.23. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.86

Clinical Summary— TBL2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

71 VUS of 97 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.000

Z-score 2.02

OE 0.49 (0.29–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.58Z-score

OE missense 0.90 (0.81–1.00)

254 obs / 281.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.29–0.86)

0≤0.351.4

Missense OE?0.90 (0.81–1.00)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 9 / 18.3Missense obs/exp: 254 / 281.3Syn Z: 0.92

This gene — mechanism propensity

0.6842th %ile

GOF

0.4678th %ile

LOF

0.4136th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

97 submitted variants in ClinVar

ClinVar

Classification Summary

VUS71

Likely Benign14

Benign3

Conflicting1

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	0	0	0
VUS	1	69	1	0	71
Likely Benign	0	6	2	6	14
Benign	0	1	0	2	3
Conflicting	—				1
Total	1	76	3	8	89

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

View in ClinVar →

163 pathogenic / likely-pathogenic (of 167) ClinVar copy-number / structural variants overlap TBL2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →