IWS1

protein-coding

interacts with SUPT6H, CTD assembly factor 1

Gene summary

Involved in regulation of mRNA export from nucleus; regulation of mRNA processing; and transcription elongation-coupled chromatin remodeling. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_017969.3

Inheritance

—

ClinVar variants

U:88B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr2:127,436,207-127,526,886

External References & Databases

Ensembl (ENSG00000163166)

Transcript & Mutation Effects

hg38 • Region Span ~90.7 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 IWS1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 86

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017969.3. 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				4 clinvar	2 clinvar	6
missense			84 clinvar	4 clinvar		88
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	88	8	2	98

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017969.3	RefSeq	NP_060439.2	14	MANE Select
ENST00000295321.9	Ensembl	ENSP00000295321.4	14	MANE Select
NM_001410923.1	RefSeq	NP_001397852.1	14	Standard
ENST00000409725.1	Ensembl	ENSP00000387206.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
RNA Polymerase II Pre-transcription Events
Formation of RNA Pol II elongation complex
RNA Polymerase II Transcription
RNA Polymerase II Transcription Elongation

Biological Process

transcription by RNA polymerase II
transcription elongation from RNA polymerase II promoter
mRNA processing
RNA splicing
regulation of mRNA export from nucleus

Molecular Function

protein binding

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295321
Coding exons: 14
Length: 90680
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125746
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.38	301	442	0.682	0.0000229	5528
Missense (PolyPhen)		53	108.49	0.48851		1387
Synonymous	0.440	149	156	0.955	0.00000870	1415
Loss of Function	5.08	5	39.4	0.127	0.00000237	487

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000061	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor which plays a key role in defining the composition of the RNA polymerase II (RNAPII) elongation complex and in modulating the production of mature mRNA transcripts. Acts as an assembly factor to recruit various factors to the RNAPII elongation complex and is recruited to the complex via binding to the transcription elongation factor SUPT6H bound to the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2) to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription. {ECO:0000269|PubMed:17184735, ECO:0000269|PubMed:17234882, ECO:0000269|PubMed:19141475}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.468
RVIS EVS: 0.18
RVIS percentile EVS: 66.07

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.688

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium