ISY1

Chr 3

ISY1 spliceosome associated protein

Also known as: FSAP33

NCBI Gene: 57461 ENSG00000240682 UniProt: Q9ULR0 OMIM: 612764

Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nuclear speck. Part of U2-type catalytic step 1 spliceosome and catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

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

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.11LOEUF

pLI 1.000

Z-score 4.74

OE 0.00 (0.00–0.11)

Highly constrained

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

Missense Constraint?

1.24Z-score

OE missense 0.72 (0.62–0.84)

114 obs / 158.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.11)

0≤0.351.4

Missense OE?0.72 (0.62–0.84)

0≤0.61.4

Synonymous OE?0.70

0≤1.21.6

LoF obs/exp: 0 / 26.1Missense obs/exp: 114 / 158.0Syn Z: 1.78

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

347 rare PASS variants

Rare truncating (LoF)

1 in 4,100

28 rare PASS variants

Rare synonymous (reference)

1 in 710

81 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ISY1. 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 190	1 in 5,300
South Asian	~43k	1 in 250	1 in 580
Remaining (unassigned)	~30k	1 in 450	1 in 2,200
European (Finnish)	~27k	1 in 1,200	1 in 3,800
Admixed American	~22k	1 in 240	≈ 1 in 7,400
African / African American	~21k	1 in 220	≈ 1 in 4,200
East Asian	~20k	1 in 220	1 in 3,300
Ashkenazi Jewish	~13k	1 in 1,400	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 210	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): 11 of 11 coding exons well covered in gnomAD exomes. Genomes: 10 of 11 (exon 1 below).? see exons ↓