HSF2BP

Chr 21

heat shock transcription factor 2 binding protein

Also known as: MEILB2, POF19

NCBI Gene: 11077ENSG00000160207UniProt: O75031

HSF2BP encodes a protein that is essential for meiotic recombination, functioning as a component of recombination bridges involved in double-strand break repair and required for proper crossover formation during meiosis. Mutations cause premature ovarian failure 19, inherited in an autosomal recessive pattern. The gene shows extremely high constraint against loss-of-function variants (pLI near 1), indicating that complete loss of protein function is likely incompatible with normal development.

ResearchSummary from RefSeq, OMIM, UniProt
DNmechanismLOEUF 1.81
Clinical Summary— HSF2BP
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
92 unique Pathogenic / Likely Pathogenic· 68 VUS of 181 total submissions
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.81LOEUF
pLI 0.000
Z-score -1.14
OE 1.31 (0.92–1.81)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.17Z-score
OE missense 1.03 (0.92–1.17)
197 obs / 190.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.31 (0.92–1.81)
0≤0.351.4
Missense OE1.03 (0.92–1.17)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 21 / 16.1Missense obs/exp: 197 / 190.3Syn Z: 0.27
DN
0.6552th %ile
GOF
0.5954th %ile
LOF
0.3549th %ile

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

DNprediction above median

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.

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

ClinVar Variant Classifications

181 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic86
Likely Pathogenic6
VUS68
Likely Benign13
Conflicting2
86
Pathogenic
6
Likely Pathogenic
68
VUS
13
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
86
0
86
Likely Pathogenic
0
2
4
0
6
VUS
1
46
21
0
68
Likely Benign
0
5
5
3
13
Benign
0
0
0
0
0
Conflicting
—2
Total1531163175

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

View in ClinVar →

Protein Context — Lollipop Plot

HSF2BP · 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 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 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