ISY1

protein-coding

ISY1 splicing factor homolog, the group of Spliceosomal B complex|Spliceosomal Bact complex|Spliceosomal P complex|Spliceosomal C complex

Gene summary

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]

MANE transcript

NM_020701.4

Inheritance

—

ClinVar variants

U:3

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr3:129,127,415-129,161,063

External References & Databases

Ensembl (ENSG00000240682)

Transcript & Mutation Effects

hg38 • Region Span ~33.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ISY1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 9

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020701.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			2 clinvar			2
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	3	0	0	3

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020701.4	RefSeq	NP_065752.1	11	MANE Select
ENST00000393295.8	Ensembl	ENSP00000376973.4	11	MANE Select
NM_001199469.2	RefSeq	NP_001186398.1	12	Standard
ENST00000273541.12	Ensembl	ENSP00000273541.8	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spliceosome - Homo sapiens (human)
DNA Repair
Metabolism of RNA
mRNA Splicing - Major Pathway
Formation of TC-NER Pre-Incision Complex

Biological Process

generation of catalytic spliceosome for second transesterification step
mRNA 3'-splice site recognition
mRNA splicing, via spliceosome
transcription-coupled nucleotide-excision repair

Molecular Function

first spliceosomal transesterification activity
RNA binding
protein binding

Cellular Component

Prp19 complex
nucleoplasm
catalytic step 2 spliceosome
post-mRNA release spliceosomal complex
post-spliceosomal complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000273541
Coding exons: 12
Length: 33879
Individuals with no LoFs: 123526
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 123528
p: 0.00000810

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.24	114	158	0.721	0.00000869	1971
Missense (PolyPhen)		24	47.623	0.50396		573
Synonymous	1.78	39	55.9	0.698	0.00000322	558
Loss of Function	4.74	0	26.1	0.00	0.00000182	282

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in pre-mRNA splicing as component of the spliceosome. {ECO:0000305|PubMed:11991638, ECO:0000305|PubMed:25599396}.;

Intolerance Scores

LoFtool: 0.397
RVIS EVS: -0.1
RVIS percentile EVS: 46.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.707

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low