RBMS1

Chr 2

RNA binding motif single stranded interacting protein 1

Also known as: C2orf12, HCC-4, MSSP, MSSP-1, MSSP-2, MSSP-3, SCR2, YC1

NCBI Gene: 5937 ENSG00000153250 UniProt: P29558

This gene encodes a member of a small family of proteins which bind single stranded DNA/RNA. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. These proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. Several transcript variants, resulting from alternative splicing and encoding different isoforms, have been described. A pseudogene for this locus is found on chromosome 12. [provided by RefSeq, Feb 2009]

Research

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

0.49

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.119

Z-score 3.57

OE 0.26 (0.15–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.66Z-score

OE missense 0.69 (0.60–0.79)

156 obs / 226.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.15–0.49)

0≤0.351.4

Missense OE?0.69 (0.60–0.79)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 7 / 27.1Missense obs/exp: 156 / 226.4Syn Z: -1.90

Background carrier burden — how many people carry a rare variant somewhere in RBMS1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 260

363 rare PASS variants

Rare truncating (LoF)

1 in 570

42 rare PASS variants

Rare synonymous (reference)

1 in 220

185 rare PASS variants

Rare missense and truncating variants are carried at similar rates in RBMS1; this gene does not show strong loss-of-function constraint by this measure. 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 300	1 in 600
South Asian	~43k	1 in 100	1 in 470
Remaining (unassigned)	~30k	1 in 350	1 in 570
European (Finnish)	~27k	1 in 390	1 in 840
Admixed American	~22k	1 in 230	1 in 1,300
African / African American	~21k	1 in 140	1 in 880
East Asian	~20k	1 in 310	1 in 520
Ashkenazi Jewish	~13k	1 in 1,400	1 in 590
Middle Eastern	~2,884	1 in 480	1 in 280

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 13 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: 12 of 13 (exon 3 below).? see exons ↓