GPBP1L1

Chr 1

GC-rich promoter binding protein 1 like 1

Also known as: SP192

GPBP1L1 encodes a protein that binds DNA and RNA and functions as a transcription factor regulating gene expression in the nucleus. Mutations cause autosomal recessive neurodevelopmental disorder with intellectual disability, seizures, and brain malformations. The gene is highly constrained against loss-of-function variants (LOEUF 0.488), suggesting complete loss of protein function is likely pathogenic.

ResearchSummary from RefSeq, UniProt
LOEUF 0.49
Clinical SummaryGPBP1L1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 78 VUS of 104 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.199
Z-score 3.44
OE 0.25 (0.130.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.13Z-score
OE missense 1.02 (0.931.13)
273 obs / 266.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.25 (0.130.49)
00.351.4
Missense OE1.02 (0.931.13)
00.61.4
Synonymous OE1.29
01.21.6
LoF obs/exp: 6 / 24.3Missense obs/exp: 273 / 266.9Syn Z: -2.18

ClinVar Variant Classifications

104 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic2
VUS78
Likely Benign4
4
Pathogenic
2
Likely Pathogenic
78
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
2
0
2
VUS
0
59
19
0
78
Likely Benign
0
1
3
0
4
Benign
0
0
0
0
0
Total06028088

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

View in ClinVar →

Protein Context — Lollipop Plot

GPBP1L1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found