BMS1

Chr 10AD

BMS1 ribosome biogenesis factor

Also known as: ACC, BMS1L

BMS1 encodes a GTPase required for 40S ribosomal subunit synthesis and pre-ribosomal RNA processing, controlling ribosome biogenesis by delivering the RCL1 endonuclease to pre-ribosomes in a GTP-dependent manner. Mutations cause autosomal dominant aplasia cutis congenita, a condition characterized by localized absence of skin typically present at birth. The gene is highly constrained against loss-of-function variants (LOEUF 0.448), indicating that such mutations are likely deleterious.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Aplasia cutis congenita, nonsyndromicMIM #107600
AD
0
Active trials
5
Pubs (1 yr)
12
P/LP submissions
8%
P/LP missense
0.45
LOEUF
DN
Mechanism· predicted
Clinical SummaryBMS1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 178 VUS of 283 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.000
Z-score 5.08
OE 0.31 (0.210.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.26Z-score
OE missense 0.97 (0.911.04)
676 obs / 695.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.210.45)
00.351.4
Missense OE0.97 (0.911.04)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 19 / 62.2Missense obs/exp: 676 / 695.3Syn Z: -1.34
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongBMS1-related aplasia cutis congenita, non-syndromicOTHERAD
DN
0.6840th %ile
GOF
0.3887th %ile
LOF
0.3259th %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

283 submitted variants in ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS178
Likely Benign38
Benign21
Conflicting3
11
Pathogenic
1
Likely Pathogenic
178
VUS
38
Likely Benign
21
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
10
0
11
Likely Pathogenic
0
0
1
0
1
VUS
1
173
4
0
178
Likely Benign
0
12
8
18
38
Benign
0
11
1
9
21
Conflicting
3
Total11972427252

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

View in ClinVar →

Protein Context — Lollipop Plot

BMS1 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC