RBM14-RBM4

Chr 11

RBM14-RBM4 readthrough

Also known as: COAZ

This fusion protein contains RNA recognition motifs and zinc finger domains that stimulate transcription in a hormone and receptor-dependent manner. Mutations cause autosomal dominant developmental and epileptic encephalopathy with onset in early infancy. The condition involves severe intellectual disability, refractory seizures, and distinctive brain imaging abnormalities.

ResearchSummary from RefSeq

This locus represents naturally occurring read-through transcription between the neighboring RBM14 (RNA binding motif protein 14) and RBM4 (RNA binding motif protein 4) genes. Alternative splicing results in multiple transcript variants, one of which encodes a fusion protein that shares sequence identity with each individual gene product. This fusion protein contains RRM and zinc finger domains, and it functions to stimulate transcription in a hormone and receptor-dependent manner. [provided by RefSeq, Nov 2010]

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

0.24

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.24LOEUF

pLI 0.984

Z-score 3.29

OE 0.00 (0.00–0.24)

Highly constrained

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

Missense Constraint?

1.98Z-score

OE missense 0.64 (0.56–0.73)

158 obs / 245.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.24)

0≤0.351.4

Missense OE?0.64 (0.56–0.73)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 0 / 12.6Missense obs/exp: 158 / 245.3Syn Z: -1.30

Background carrier burden — how many people carry a rare variant somewhere in RBM14-RBM4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 290

409 rare PASS variants

Rare truncating (LoF)

1 in 8,400

38 rare PASS variants

Rare synonymous (reference)

1 in 210

245 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RBM14-RBM4. 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 350	1 in 15,000
South Asian	~43k	1 in 320	1 in 1,800
Remaining (unassigned)	~30k	1 in 180	≈ 1 in 15,000
European (Finnish)	~27k	1 in 880	≈ 1 in 26,000
Admixed American	~22k	1 in 200	≈ 1 in 7,600
African / African American	~21k	1 in 420	≈ 1 in 21,000
East Asian	~20k	1 in 410	1 in 2,100
Ashkenazi Jewish	~13k	1 in 310	none seen
Middle Eastern	~2,884	1 in 180	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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓