ISY1

Chr 3

ISY1 spliceosome associated protein

Also known as: FSAP33

NCBI Gene: 57461 ENSG00000240682 OMIM: 612764

Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleus. Part of U2-type catalytic step 1 spliceosome and catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.11

Clinical Summary— ISY1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

9 VUS of 13 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.3992th %ile

GOF

0.3888th %ile

LOF

0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.11

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

13 submitted variants in ClinVar

ClinVar

Classification Summary

VUS9

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	9	0	9
Likely Benign	0	1	1
Benign	0	0	0
Total	9	1	10

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap ISY1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →