YBX1

Chr 1

Y-box binding protein 1

Also known as: BP-8, CBF-A, CSDA2, CSDB, DBPB, EFI-A, MDR-NF1, NSEP-1

NCBI Gene: 4904 ENSG00000065978 UniProt: P67809 OMIM: 154030

Y-box binding protein 1 functions as a DNA- and RNA-binding protein that regulates transcription, translation, mRNA splicing and stability, and DNA repair. Mutations cause autosomal dominant cold-induced sweating syndrome with early childhood onset, characterized by profuse sweating triggered by cold temperatures and ambient temperature changes. This gene is highly constrained against loss-of-function variation (pLI 0.95, LOEUF 0.35), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a highly conserved cold shock domain protein that has broad nucleic acid binding properties. The encoded protein functions as both a DNA and RNA binding protein and has been implicated in numerous cellular processes including regulation of transcription and translation, pre-mRNA splicing, DNA reparation and mRNA packaging. This protein is also a component of messenger ribonucleoprotein (mRNP) complexes and may have a role in microRNA processing. This protein can be secreted through non-classical pathways and functions as an extracellular mitogen. Aberrant expression of the gene is associated with cancer proliferation in numerous tissues. This gene may be a prognostic marker for poor outcome and drug resistance in certain cancers. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on multiple chromosomes. [provided by RefSeq, Sep 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.35

Clinical Summary— YBX1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

41 VUS of 59 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.35LOEUF

pLI 0.946

Z-score 3.50

OE 0.11 (0.04–0.35)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.71Z-score

OE missense 0.64 (0.55–0.75)

118 obs / 183.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.35)

0≤0.351.4

Missense OE?0.64 (0.55–0.75)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 2 / 18.0Missense obs/exp: 118 / 183.3Syn Z: 0.29

This gene — mechanism propensity

0.3991th %ile

GOF

0.3193th %ile

LOF

0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.35

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

59 submitted variants in ClinVar

ClinVar

Classification Summary

VUS41

Likely Benign4

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	41	0	41
Likely Benign	0	4	4
Benign	1	0	1
Total	42	4	46

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap YBX1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →