TBPL1

Chr 6

TATA-box binding protein like 1

Also known as: MGC:8389, MGC:9620, STUD, TLF, TLP, TRF2

NCBI Gene: 9519ENSG00000028839UniProt: P62380

This gene encodes a member of the TATA box-binding protein family. TATA box-binding proteins play a critical role in transcription by RNA polymerase II as components of the transcription factor IID (TFIID) complex. The encoded protein does not bind to the TATA box and initiates transcription from TATA-less promoters. This gene plays a critical role in spermatogenesis, and single nucleotide polymorphisms in this gene may be associated with male infertility. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 3. [provided by RefSeq, Nov 2011]

19
ClinVar variants
14
Pathogenic / LP
0.38
pLI score
0
Active trials
Clinical Summary— TBPL1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 5 VUS of 19 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.69LOEUF
pLI 0.379
Z-score 2.18
OE 0.22 (0.09–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.50Z-score
OE missense 0.30 (0.22–0.41)
30 obs / 100.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.22 (0.09–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.30 (0.22–0.41)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.61
0≤1.21.6
LoF obs/exp: 2 / 9.1Missense obs/exp: 30 / 100.6Syn Z: 1.74

ClinVar Variant Classifications

19 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
VUS5
14
Pathogenic
5
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
0
0
0
VUS
0
5
0
0
5
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0514019

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

View in ClinVar →

Protein Context — Lollipop Plot

TBPL1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools