HSF2BP

Chr 21AR

heat shock transcription factor 2 binding protein

Also known as: MEILB2, POF19

NCBI Gene: 11077 ENSG00000160207 UniProt: O75031 OMIM: 604554

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

HSF2 binding protein (HSF2BP) associates with HSF2. The interaction occurs between the trimerization domain of HSF2 and the amino terminal hydrophilic region of HSF2BP that comprises two leucine zipper motifs. HSF2BP may therefore be involved in modulating HSF2 activation. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.811 OMIM phenotype

Clinical Summary— HSF2BP

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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

2 unique Pathogenic / Likely Pathogenic· 47 VUS of 63 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?

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 OE?1.31 (0.92–1.81)

0≤0.351.4

Missense OE?1.03 (0.92–1.17)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 21 / 16.1Missense obs/exp: 197 / 190.3Syn Z: 0.27

This gene — mechanism propensity

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

63 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic2

VUS47

Likely Benign8

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	2	0	2
VUS	1	46	0	47
Likely Benign	0	5	3	8
Benign	0	0	0	0
Total	1	53	3	57

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

View in ClinVar →

90 pathogenic / likely-pathogenic (of 118) ClinVar copy-number / structural variants overlap HSF2BP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →