TBL3

Chr 16

transducin beta like 3

Also known as: SAZD, UTP13

NCBI Gene: 10607 ENSG00000183751 UniProt: Q12788 OMIM: 605915

TBL3 encodes a WD40 repeat-containing protein that is part of the small subunit processome involved in ribosome biogenesis, where it assists in the processing and assembly of precursor ribosomal RNA in the nucleolus. Mutations cause an autosomal recessive neurodevelopmental disorder characterized by intellectual disability, developmental delay, and microcephaly. This gene is not highly constrained against loss-of-function variation, which is consistent with the recessive inheritance pattern observed in affected individuals.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. This gene has multiple polyadenylation sites. It might have multiple alternatively spliced transcript variants but the variants have not been fully described yet. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.74

Clinical Summary— TBL3

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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

268 VUS of 334 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 2.97

OE 0.53 (0.38–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.21Z-score

OE missense 1.03 (0.95–1.10)

540 obs / 526.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.53 (0.38–0.74)

0≤0.351.4

Missense OE?1.03 (0.95–1.10)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 24 / 45.6Missense obs/exp: 540 / 526.7Syn Z: -2.42

ClinVar Variant Classifications

334 submitted variants in ClinVar

ClinVar

Classification Summary

VUS268

Likely Benign23

Benign3

268

VUS

Likely Benign

Benign

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	267	0	0	268
Likely Benign	1	18	0	4	23
Benign	0	0	1	2	3
Total	2	285	1	6	294

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

View in ClinVar →

42 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap TBL3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →