SKIC3

SKI3 subunit of superkiller complex, the group of SKI complex subunits|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 5:95461754-95555050

Previous symbols: [ "KIAA0372", "TTC37" ]

Links

ENSG00000198677 ∙ NCBI:9652 ∙ OMIM:614589 ∙ HGNC:23639 ∙ Uniprot:Q6PGP7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• trichohepatoenteric syndrome 1 (Definitive), mode of inheritance: AR
• trichohepatoenteric syndrome 1 (Strong), mode of inheritance: AR
• trichohepatoenteric syndrome 1 (Definitive), mode of inheritance: AR
• trichohepatoenteric syndrome (Supportive), mode of inheritance: AR
• trichohepatoenteric syndrome 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Trichohepatoenteric syndrome 1	AR	Allergy/Immunology/Infectious; Gastrointestinal	Individuals may also have immunodeficiency, and may benefit from prophylaxis and early and aggressive treatment of infections; Intractable diarrhea in infancy may require total parenteral nutrition; Patients may require hepatic transplant	Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal	70733018021782; 9021008; 9481629; 14521564; 15069414; 17236206; 17318842; 20176027; 21120949
The condition may be clinically recognizable, and prognosis may be poor in some individuals despite optimal therapy

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SKIC3 gene.

• not provided (809 variants)
• Trichohepatoenteric syndrome 1 (54 variants)
• not specified (20 variants)
• Inborn genetic diseases (19 variants)
• Trichohepatoenteric syndrome (9 variants)
• SKIC3-related condition (4 variants)
• Inherited Immunodeficiency Diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SKIC3 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			3	159	3	165
missense		1	323	14	5	343
nonsense	19	8				27
start loss						0
frameshift	27	7	1			35
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	17	1			19
splice region			20	45	6	71
non coding			5	119	34	158
Total	47	33	335	292	42

Highest pathogenic variant AF is 0.0000329

Variants in SKIC3

This is a list of pathogenic ClinVar variants found in the SKIC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-95464530-C-T			Benign (Jun 19, 2021)
5-95464606-G-C		Trichohepatoenteric syndrome 1	Uncertain significance (Oct 16, 2021)
5-95464607-T-C			Likely benign (Mar 25, 2021)
5-95464607-T-G			Uncertain significance (Oct 07, 2021)
5-95464616-G-C		SKIC3-related disorder	Likely benign (Oct 22, 2023)
5-95464620-A-C			Uncertain significance (Sep 01, 2021)
5-95464630-T-A		Inborn genetic diseases	Uncertain significance (Mar 07, 2023)
5-95464630-T-C			Uncertain significance (Aug 27, 2021)
5-95464632-A-G			Uncertain significance (Nov 18, 2019)
5-95464639-A-G			Likely benign (Dec 12, 2023)
5-95464645-T-G			Likely benign (Jul 15, 2023)
5-95464647-G-A			Uncertain significance (May 15, 2022)
5-95464647-G-C			Uncertain significance (Mar 26, 2022)
5-95464649-A-T			Uncertain significance (Mar 26, 2022)
5-95464657-G-A			Uncertain significance (Aug 12, 2022)
5-95464663-T-C			Uncertain significance (Jul 27, 2022)
5-95464663-TG-T			Uncertain significance (Aug 19, 2022)
5-95464674-A-G			Uncertain significance (Sep 26, 2021)
5-95464674-A-T			Uncertain significance (Oct 05, 2021)
5-95464688-G-A			Likely benign (Feb 11, 2023)
5-95464690-A-C			Likely benign (Feb 27, 2023)
5-95464690-A-T			Likely benign (Aug 03, 2023)
5-95464692-T-C			Likely benign (Oct 20, 2023)
5-95464697-T-C			Likely benign (Jun 23, 2023)
5-95464698-A-T			Likely benign (Jul 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SKIC3	protein_coding	protein_coding	ENST00000358746	40	91113

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.73e-29	0.996	125505	0	243	125748	0.000967

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.482	746	784	0.952	0.0000384	10183
Missense in Polyphen		206	235.66	0.87415		3120
Synonymous	0.0231	287	288	0.998	0.0000145	2907
Loss of Function	3.36	62	97.9	0.634	0.00000468	1253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00120	0.00120
Ashkenazi Jewish	0.00129	0.00129
East Asian	0.00283	0.00283
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000664	0.000659
Middle Eastern	0.00283	0.00283
South Asian	0.00229	0.00226
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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).
• Pathway: RNA degradation - Homo sapiens (human);Metabolism of RNA;mRNA decay by 3, to 5, exoribonuclease;Deadenylation-dependent mRNA decay (Consensus)

Recessive Scores

• pRec: 0.0888

Intolerance Scores

• loftool: 0.944
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.01

Haploinsufficiency Scores

• pHI: 0.352
• hipred: N
• hipred_score: 0.415
• ghis: 0.604

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.776

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ttc37

Gene ontology

• Biological process: exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;transcriptionally active chromatin;Ski complex
• Molecular function: protein binding