SMU1

Chr 9

SMU1 DNA replication regulator and spliceosomal factor

Also known as: BWD, SMU-1, fSAP57

NCBI Gene: 55234 ENSG00000122692 UniProt: Q2TAY7 OMIM: 617811

SMU1 encodes a protein that functions as a component of the spliceosome and is required for pre-mRNA splicing, mitotic spindle assembly, and normal progression through mitosis. Mutations cause autosomal recessive congenital pontocerebellar hypoplasia with microcephaly, typically presenting in the neonatal period with severe developmental delays and neurological impairment. This gene is highly constrained against loss-of-function variants, indicating that functional copies are essential for normal development.

OMIM ResearchSummary from RefSeq, UniProt

Involved in mRNA splicing, via spliceosome. Located in nucleus. Part of U2-type precatalytic spliceosome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.11

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.11LOEUF

pLI 1.000

Z-score 4.87

OE 0.00 (0.00–0.11)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

4.31Z-score

OE missense 0.27 (0.23–0.33)

76 obs / 278.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.11)

0≤0.351.4

Missense OE?0.27 (0.23–0.33)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 0 / 27.7Missense obs/exp: 76 / 278.5Syn Z: 0.96

Background carrier burden — how many people carry a rare variant somewhere in SMU1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 850

250 rare PASS variants

Rare truncating (LoF)

1 in 240,000

3 rare PASS variants

Rare synonymous (reference)

1 in 150

208 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SMU1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 1,000	≈ 1 in 270,000
South Asian	~43k	1 in 1,100	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 630	none seen
European (Finnish)	~27k	1 in 3,000	none seen
Admixed American	~22k	1 in 1,100	none seen
African / African American	~21k	1 in 520	none seen
East Asian	~20k	1 in 630	none seen
Ashkenazi Jewish	~13k	≈ 1 in 4,400	none seen
Middle Eastern	~2,884	≈ 1 in 860	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓