BSX

Chr 11

brain specific homeobox

Also known as: BSX1

NCBI Gene: 390259 ENSG00000188909 UniProt: Q3C1V8 OMIM: 611074

BSX encodes a DNA-binding transcription factor essential for postnatal growth, nursing behavior, and energy balance regulation through control of neuropeptide Y and agouti-related peptide neuronal function. Mutations cause neurodevelopmental disorders affecting growth and feeding behaviors, with autosomal recessive inheritance patterns reported. The gene shows relatively low constraint against loss-of-function variants, suggesting tolerance to heterozygous disruption.

OMIM ResearchSummary from RefSeq, UniProt

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in cell differentiation; regulation of transcription by RNA polymerase II; and stem cell population maintenance. Predicted to act upstream of or within several processes, including eating behavior; mammary gland involution; and positive regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. Predicted to be part of transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.33

Clinical Summary— BSX

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

24 VUS of 28 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?

1.33LOEUF

pLI 0.008

Z-score 1.01

OE 0.58 (0.29–1.33)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.48Z-score

OE missense 0.88 (0.76–1.03)

115 obs / 130.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.29–1.33)

0≤0.351.4

Missense OE?0.88 (0.76–1.03)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 4 / 6.8Missense obs/exp: 115 / 130.6Syn Z: -0.35

This gene — mechanism propensity

0.7036th %ile

GOF

0.4678th %ile

LOF

0.54top 25%

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

28 submitted variants in ClinVar

ClinVar

Classification Summary

VUS24

Likely Benign1

Benign3

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	24	0	24
Likely Benign	0	1	1
Benign	1	2	3
Total	25	3	28

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

View in ClinVar →

50 pathogenic / likely-pathogenic (of 53) ClinVar copy-number / structural variants overlap BSX — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →