TBL1XR1

Chr 3

TBL1X/Y related 1

Also known as: C21, DC42, IRA1, MRD41, TBLR1

NCBI Gene: 79718ENSG00000177565UniProt: Q9BZK7

This gene is a member of the WD40 repeat-containing gene family and shares sequence similarity with transducin (beta)-like 1X-linked (TBL1X). The protein encoded by this gene is thought to be a component of both nuclear receptor corepressor (N-CoR) and histone deacetylase 3 (HDAC 3) complexes, and is required for transcriptional activation by a variety of transcription factors. Mutations in these gene have been associated with some autism spectrum disorders, and one finding suggests that haploinsufficiency of this gene may be a cause of intellectual disability with dysmorphism. Mutations in this gene as well as recurrent translocations involving this gene have also been observed in some tumors. [provided by RefSeq, Mar 2016]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPierpont syndrome
UniProtIntellectual developmental disorder, autosomal dominant 41

Clinical highlights

Gene-disease validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
—
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.11
LOEUF· LoF intol.
Multiple*
Mechanism· G2P
📖
GeneReview available — TBL1XR1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.11LOEUF
pLI 1.000
Z-score 4.91
OE 0.00 (0.00–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
4.20Z-score
OE missense 0.27 (0.22–0.33)
69 obs / 259.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.11)
0≤0.351.4
Missense OE?0.27 (0.22–0.33)
0≤0.61.4
Synonymous OE?1.05
0≤1.21.6
LoF obs/exp: 0 / 28.1Missense obs/exp: 69 / 259.6Syn Z: -0.38

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TBL1XR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients