SKIC8

SKI8 subunit of superkiller complex, the group of Paf1/RNA polymerase II complex |SKI complex subunits|WD repeat domain containing

Basic information

Region (hg38): 15:78277835-78299703

Previous symbols: [ "WDR61" ]

Links

ENSG00000140395 ∙ NCBI:80349 ∙ OMIM:609540 ∙ HGNC:30300 ∙ Uniprot:Q9GZS3 ∙ 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 SKIC8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SKIC8 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						0
missense			8			8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	8	0	0

Variants in SKIC8

This is a list of pathogenic ClinVar variants found in the SKIC8 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-78280080-C-T		not specified	Uncertain significance (Dec 05, 2024)
15-78280135-T-C		not specified	Uncertain significance (May 10, 2022)
15-78280283-G-T		not specified	Uncertain significance (Oct 20, 2023)
15-78280287-C-T		not specified	Uncertain significance (May 24, 2023)
15-78280293-C-G		not specified	Uncertain significance (Apr 09, 2024)
15-78280314-C-G		not specified	Uncertain significance (Apr 23, 2024)
15-78280315-G-C		not specified	Uncertain significance (Sep 17, 2021)
15-78280342-T-C		not specified	Uncertain significance (Sep 09, 2024)
15-78280397-C-A		not specified	Uncertain significance (Mar 27, 2023)
15-78280417-A-G		not specified	Uncertain significance (Aug 02, 2021)
15-78280425-G-A		not specified	Uncertain significance (Feb 10, 2025)
15-78280453-C-T		not specified	Uncertain significance (Sep 16, 2021)
15-78283437-T-C		not specified	Uncertain significance (Jul 10, 2023)
15-78283455-G-A		not specified	Uncertain significance (Nov 10, 2022)
15-78285298-C-T		not specified	Uncertain significance (Feb 05, 2024)
15-78285304-C-G		not specified	Uncertain significance (Jan 24, 2025)
15-78288346-G-C		not specified	Uncertain significance (Mar 08, 2025)
15-78289678-A-C		not specified	Uncertain significance (Jan 18, 2022)
15-78290095-A-T		not specified	Uncertain significance (Jun 05, 2024)
15-78292621-C-T		not specified	Uncertain significance (Jun 03, 2024)
15-78292638-T-C		not specified	Uncertain significance (Aug 21, 2024)
15-78292678-G-A		not specified	Uncertain significance (Jan 10, 2025)
15-78293216-C-G		not specified	Uncertain significance (Dec 31, 2024)
15-78293267-C-T		not specified	Uncertain significance (Jan 21, 2025)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SKIC8	protein_coding	protein_coding	ENST00000267973	10	21960

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00480	0.990	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.95	96	167	0.575	0.00000839	2009
Missense in Polyphen		20	50.688	0.39457		630
Synonymous	0.738	54	61.4	0.880	0.00000330	579
Loss of Function	2.43	7	18.2	0.385	7.71e-7	207

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000793	0.0000791
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non- phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both indepentently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3), dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcription. Component of the SKI complex which is thought to be involved in exosome-mediated RNA decay and associates with transcriptionally active genes in a manner dependent on PAF1C. {ECO:0000269|PubMed:16024656, ECO:0000269|PubMed:16307923, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742}.
• Pathway: RNA degradation - Homo sapiens (human);Gene expression (Transcription);RNA Polymerase II Pre-transcription Events;Post-translational protein modification;Formation of RNA Pol II elongation complex ;Metabolism of proteins;RNA Polymerase II Transcription;Metabolism of RNA;RNA Polymerase II Transcription Elongation;Protein ubiquitination;mRNA decay by 3, to 5, exoribonuclease;Deadenylation-dependent mRNA decay;E3 ubiquitin ligases ubiquitinate target proteins (Consensus)

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.418
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.15

Haploinsufficiency Scores

• pHI: 0.422
• hipred: Y
• hipred_score: 0.669
• ghis: 0.691

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wdr61

Gene ontology

• Biological process: transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;Wnt signaling pathway;protein ubiquitination;positive regulation of transcription elongation from RNA polymerase II promoter;exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;negative regulation of myeloid cell differentiation;positive regulation of transcription by RNA polymerase II;positive regulation of histone H3-K4 methylation;histone H3-K4 trimethylation;positive regulation of histone H3-K79 methylation
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;Cdc73/Paf1 complex;transcriptionally active chromatin;Ski complex
• Molecular function: protein binding