IWS1

interacts with SUPT6H, CTD assembly factor 1

Basic information

Region (hg38): 2:127436207-127526886

Links

ENSG00000163166 ∙ NCBI:55677 ∙ ∙ HGNC:25467 ∙ Uniprot:Q96ST2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IWS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IWS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					2	2
missense			30	2		32
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	30	2	2

Variants in IWS1

This is a list of pathogenic ClinVar variants found in the IWS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-127481091-C-G		not specified	Uncertain significance (Jun 18, 2024)
2-127481168-G-A		not specified	Uncertain significance (Aug 18, 2021)
2-127486572-A-G		not specified	Uncertain significance (Dec 10, 2024)
2-127486612-G-A		not specified	Uncertain significance (Jul 17, 2024)
2-127489841-C-T		not specified	Uncertain significance (Dec 03, 2024)
2-127489844-C-T		not specified	Uncertain significance (Nov 29, 2023)
2-127489926-T-C		not specified	Uncertain significance (Jul 23, 2024)
2-127492024-T-C		not specified	Uncertain significance (Oct 04, 2022)
2-127493304-C-T		not specified	Uncertain significance (Feb 21, 2024)
2-127493373-T-A		not specified	Uncertain significance (Jun 13, 2024)
2-127494907-T-G		not specified	Uncertain significance (Jun 24, 2022)
2-127496066-C-T		not specified	Uncertain significance (Oct 08, 2024)
2-127498223-T-A		not specified	Uncertain significance (May 20, 2024)
2-127498236-C-A		not specified	Uncertain significance (Aug 20, 2024)
2-127502832-C-T		not specified	Uncertain significance (Jun 21, 2022)
2-127502870-T-G		not specified	Uncertain significance (Jan 04, 2022)
2-127503439-T-C		not specified	Uncertain significance (Apr 18, 2023)
2-127503469-C-G		not specified	Uncertain significance (Apr 08, 2024)
2-127503471-T-C		not specified	Uncertain significance (Aug 30, 2022)
2-127503505-T-C		not specified	Uncertain significance (Sep 30, 2024)
2-127503518-T-C			Benign (Apr 30, 2018)
2-127503543-T-C		not specified	Uncertain significance (Mar 27, 2023)
2-127503561-C-T		not specified	Uncertain significance (Jan 26, 2023)
2-127504772-A-C		not specified	Uncertain significance (Jun 30, 2022)
2-127504864-C-T		not specified	Uncertain significance (Feb 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IWS1	protein_coding	protein_coding	ENST00000295321	14	90680

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00273	125735	0	11	125746	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.38	301	442	0.682	0.0000229	5528
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000122	0.000122
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000538	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

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}.
• Pathway: 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 (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.468
• rvis_EVS: 0.18
• rvis_percentile_EVS: 66.07

Haploinsufficiency Scores

• pHI: 0.295
• hipred: Y
• hipred_score: 0.649
• ghis: 0.540

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.688

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Iws1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;mRNA processing;RNA splicing;regulation of mRNA export from nucleus;regulation of mRNA processing;mRNA transport;regulation of histone H4 acetylation;regulation of histone H3-K36 trimethylation
• Cellular component: nucleus;nucleoplasm
• Molecular function: protein binding