ISY1-RAB43

Chr 3

ISY1-RAB43 readthrough

This locus represents naturally occurring read-through transcription between the neighboring ISY1 (ISY1 splicing factor homolog) and RAB43 (RAB43, member RAS oncogene family) gene on chromosome 3. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product, but its C-terminus is distinct due to a frameshift relative to the downstream gene. [provided by RefSeq, Mar 2011]

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

0.17

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 4.69

OE 0.04 (0.01–0.17)

Highly constrained

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

Missense Constraint?

1.42Z-score

OE missense 0.71 (0.62–0.82)

135 obs / 190.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.17)

0≤0.351.4

Missense OE?0.71 (0.62–0.82)

0≤0.61.4

Synonymous OE?0.68

0≤1.21.6

LoF obs/exp: 1 / 27.6Missense obs/exp: 135 / 190.0Syn Z: 2.11

Background carrier burden — how many people carry a rare variant somewhere in ISY1-RAB43?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 350

356 rare PASS variants

Rare truncating (LoF)

1 in 12,000

22 rare PASS variants

Rare synonymous (reference)

1 in 550

125 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ISY1-RAB43. 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 12,000
South Asian	~43k	1 in 430	1 in 6,100
Remaining (unassigned)	~30k	1 in 370	≈ 1 in 7,500
European (Finnish)	~27k	1 in 1,300	none seen
Admixed American	~22k	1 in 240	≈ 1 in 22,000
African / African American	~21k	1 in 260	≈ 1 in 17,000
East Asian	~20k	1 in 190	none seen
Ashkenazi Jewish	~13k	1 in 1,100	none seen
Middle Eastern	~2,884	1 in 170	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): 12 of 12 coding exons well covered in gnomAD exomes. Genomes: 11 of 12 (exon 1 below).? see exons ↓