GFI1B

Chr 9ADAR

growth factor independent 1B transcriptional repressor

Also known as: BDPLT17, ZNF163B

NCBI Gene: 8328ENSG00000165702UniProt: Q5VTD9OMIM: 604383

This gene encodes a zinc-finger transcriptional regulator that controls expression of genes essential for erythrocyte and megakaryocyte development and maturation by forming complexes with GATA-1, RUNX1, and histone deacetylases. Mutations cause autosomal dominant bleeding disorder, platelet-type, 17, which results from impaired megakaryocyte differentiation leading to platelet dysfunction. The pathogenic mechanism involves dominant-negative effects that disrupt normal transcriptional regulation of hematopoietic cell development.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismAD/ARLOEUF 0.861 OMIM phenotype
Clinical Summary— GFI1B
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Gene-Disease Validity (ClinGen)
platelet-type bleeding disorder 17 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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
48 unique Pathogenic / Likely Pathogenic· 86 VUS of 186 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.001
Z-score 1.97
OE 0.48 (0.28–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.50Z-score
OE missense 0.90 (0.80–1.02)
192 obs / 212.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.28–0.86)
0≤0.351.4
Missense OE0.90 (0.80–1.02)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 8 / 16.7Missense obs/exp: 192 / 212.4Syn Z: -0.69
DN
0.78top 25%
GOF
0.5955th %ile
LOF
0.4627th %ile

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

DNprediction above median · 1 literature citation

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.

Literature Evidence

DNA dominant-negative GFI1B mutation in the gray platelet syndrome.PMID:24325358

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

ClinVar Variant Classifications

186 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic4
VUS86
Likely Benign19
Benign29
Conflicting3
44
Pathogenic
4
Likely Pathogenic
86
VUS
19
Likely Benign
29
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
3
36
0
44
Likely Pathogenic
0
2
2
0
4
VUS
2
66
18
0
86
Likely Benign
0
7
4
8
19
Benign
0
6
22
1
29
Conflicting
—3
Total784829185

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

View in ClinVar →

Protein Context — Lollipop Plot

GFI1B · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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