SKIC2

SKI2 subunit of superkiller complex, the group of SKI complex subunits|Ski2 like RNA helicases

Basic information

Region (hg38): 6:31959115-31969818

Previous symbols: [ "SKIV2", "SKIV2L" ]

Links

ENSG00000204351 ∙ NCBI:6499 ∙ OMIM:600478 ∙ HGNC:10898 ∙ Uniprot:Q15477 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• trichohepatoenteric syndrome 2 (Definitive), mode of inheritance: AR
• trichohepatoenteric syndrome 2 (Strong), mode of inheritance: AR
• trichohepatoenteric syndrome 2 (Moderate), mode of inheritance: AR
• trichohepatoenteric syndrome 2 (Strong), mode of inheritance: AR
• trichohepatoenteric syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Trichohepatoenteric syndrome 2	AR	Allergy/Immunology/Infectious; Gastrointestinal	Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; Parenteral nutrition may be required	Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal	18982349; 22444670; 23679950

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SKIC2 gene.

• not provided (618 variants)
• Trichohepatoenteric syndrome 2 (98 variants)
• Inborn genetic diseases (15 variants)
• Trichohepatoenteric syndrome (10 variants)
• not specified (8 variants)
• SKIC2-related condition (4 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SKIC2 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			9	130	10	149
missense		1	265	7	6	279
nonsense	17	3				20
start loss			1			1
frameshift	24	5	1			30
inframe indel	1		6			7
splice donor/acceptor (+/-2bp)	2	12	1			15
splice region			10	19	3	32
non coding			7	99	12	118
Total	44	21	290	236	28

Highest pathogenic variant AF is 0.000138

Variants in SKIC2

This is a list of pathogenic ClinVar variants found in the SKIC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-31959150-T-C		Trichohepatoenteric syndrome	Uncertain significance (Jun 14, 2016)
6-31959171-A-T		Trichohepatoenteric syndrome	Uncertain significance (Jun 14, 2016)
6-31959179-G-A		Trichohepatoenteric syndrome 2	Uncertain significance (Jan 13, 2018)
6-31959193-A-G			Uncertain significance (Oct 13, 2022)
6-31959201-G-A			Likely benign (Oct 17, 2023)
6-31959215-G-A			Likely pathogenic (Feb 17, 2023)
6-31959215-G-T			Likely pathogenic (Nov 24, 2023)
6-31959217-G-T			Uncertain significance (Oct 26, 2022)
6-31959219-G-A			Uncertain significance (Apr 09, 2022)
6-31959222-G-C			Likely benign (Jul 03, 2023)
6-31959223-G-A			Likely benign (Jun 29, 2023)
6-31959224-A-G			Likely benign (Nov 27, 2021)
6-31959228-G-A			Likely benign (May 05, 2022)
6-31959228-G-C			Likely benign (Oct 25, 2023)
6-31959230-G-A			Likely benign (Jul 03, 2022)
6-31959232-G-A			Likely benign (Sep 08, 2023)
6-31959232-GA-G			Likely benign (Apr 07, 2023)
6-31959277-C-T			Likely benign (Aug 17, 2023)
6-31959279-T-C			Likely benign (Sep 09, 2023)
6-31959283-A-T		Trichohepatoenteric syndrome 2	Benign (Jan 31, 2024)
6-31959289-C-T			Likely benign (Mar 21, 2022)
6-31959292-C-T			Likely benign (Oct 04, 2023)
6-31959299-C-T			Likely benign (Jan 06, 2024)
6-31959301-A-G			Likely benign (Apr 09, 2023)
6-31959303-C-T			Uncertain significance (May 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SKIC2	protein_coding	protein_coding	ENST00000375394	28	10676

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.29e-22	0.815	125558	0	190	125748	0.000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.85	614	757	0.811	0.0000466	7995
Missense in Polyphen		225	283.48	0.79369		2913
Synonymous	2.83	232	294	0.790	0.0000169	2635
Loss of Function	2.37	45	65.8	0.684	0.00000366	690

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00267	0.00264
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000608	0.000598
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000798	0.000774
Middle Eastern	0.000608	0.000598
South Asian	0.000459	0.000457
Other	0.000496	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Helicase; has ATPase activity. 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 PAF1 complex (PAF1C).
• Disease: DISEASE: Trichohepatoenteric syndrome 2 (THES2) [MIM:614602]: A syndrome characterized by intrauterine growth retardation, severe diarrhea in infancy requiring total parenteral nutrition, facial dysmorphism, immunodeficiency, and hair abnormalities, mostly trichorrhexis nodosa. Hepatic involvement contributes to the poor prognosis of affected patients. {ECO:0000269|PubMed:22444670}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: RNA degradation - Homo sapiens (human);Metabolism of proteins;Metabolism of RNA;Chaperonin-mediated protein folding;Association of TriC/CCT with target proteins during biosynthesis;Protein folding;mRNA decay by 3, to 5, exoribonuclease;Deadenylation-dependent mRNA decay (Consensus)

Intolerance Scores

• loftool: 0.965
• rvis_EVS: 0.17
• rvis_percentile_EVS: 64.98

Haploinsufficiency Scores

• pHI: 0.118
• hipred: Y
• hipred_score: 0.591
• ghis: 0.509

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.903

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Skiv2l
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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: RNA catabolic process;exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;nuclear-transcribed mRNA catabolic process, 3'-5' exonucleolytic nonsense-mediated decay
• Cellular component: nucleus;cytosol;Ski complex
• Molecular function: RNA binding;ATP-dependent RNA helicase activity;ATP binding