RBM14

Chr 11

RNA binding motif protein 14

Also known as: COAA, PSP2, SIP, SYTIP1, TMEM137

NCBI Gene: 10432 ENSG00000239306 UniProt: Q96PK6

RBM14 encodes a ribonucleoprotein that functions as a nuclear transcriptional coactivator, RNA splicing modulator, and regulator of centriole biogenesis to maintain mitotic spindle integrity. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants (pLI 0.998, LOEUF 0.204), indicating that haploinsufficiency is likely not tolerated in the general population.

ResearchSummary from RefSeq, UniProt

This gene encodes a ribonucleoprotein that functions as a general nuclear coactivator, and an RNA splicing modulator. This protein contains two RNA recognition motifs (RRM) at the N-terminus, and multiple hexapeptide repeat domain at the C-terminus that interacts with thyroid hormone receptor-binding protein (TRBP), and is required for transcription activation. Alternatively spliced transcript variants encoding different isoforms (with opposing effects on transcription) have been described for this gene. [provided by RefSeq, Oct 2011]

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

0.20

LOEUF· LoF intol.

LOF

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

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.20LOEUF

pLI 0.998

Z-score 4.27

OE 0.04 (0.01–0.20)

Highly constrained

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

Missense Constraint?

2.11Z-score

OE missense 0.72 (0.65–0.79)

318 obs / 443.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.20)

0≤0.351.4

Missense OE?0.72 (0.65–0.79)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 1 / 23.2Missense obs/exp: 318 / 443.1Syn Z: -0.70

Background carrier burden — how many people carry a rare variant somewhere in RBM14?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 83

886 rare PASS variants

Rare truncating (LoF)

1 in 4,100

29 rare PASS variants

Rare synonymous (reference)

1 in 130

438 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RBM14. 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 100	1 in 3,400
South Asian	~43k	1 in 95	1 in 2,100
Remaining (unassigned)	~30k	1 in 59	≈ 1 in 6,200
European (Finnish)	~27k	1 in 180	≈ 1 in 6,000
Admixed American	~22k	1 in 82	≈ 1 in 4,600
African / African American	~21k	1 in 81	1 in 860
East Asian	~20k	1 in 110	none seen
Ashkenazi Jewish	~13k	1 in 440	none seen
Middle Eastern	~2,884	1 in 91	≈ 1 in 580

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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓