SNF8

SNF8 subunit of ESCRT-II, the group of ESCRT-II

Basic information

Region (hg38): 17:48929316-48944842

Links

ENSG00000159210 ∙ NCBI:11267 ∙ OMIM:610904 ∙ HGNC:17028 ∙ Uniprot:Q96H20 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 115; Neurodevelopmental disorder plus optic atrophy	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic; Ophthalmologic	38423010

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SNF8 gene.

• SNF8-associated disease (6 variants)
• Developmental and epileptic encephalopathy 115 (4 variants)
• Neurodevelopmental disorder plus optic atrophy (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SNF8 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	3		10			13
nonsense	1					1
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding						0
Total	6	0	10	0	0

Highest pathogenic variant AF is 0.00000658

Variants in SNF8

This is a list of pathogenic ClinVar variants found in the SNF8 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-48930497-T-G		not specified	Uncertain significance (Jun 21, 2022)
17-48930553-G-C		not specified	Uncertain significance (Nov 09, 2021)
17-48930558-C-T		not specified	Uncertain significance (Apr 07, 2023)
17-48930566-G-A		not specified	Uncertain significance (Jun 06, 2023)
17-48930569-GCCTGTAAGTC-TCCA		SNF8-associated disease • Neurodevelopmental disorder plus optic atrophy	Pathogenic (Dec 07, 2023)
17-48931653-C-T		Aganglionic megacolon	Uncertain significance (May 16, 2019)
17-48931659-C-A		SNF8-associated disease • Developmental and epileptic encephalopathy 115	Pathogenic (Dec 07, 2023)
17-48931710-C-T		SNF8-associated disease • Developmental and epileptic encephalopathy 115	Pathogenic (Dec 07, 2023)
17-48933239-T-C		not specified	Uncertain significance (Jun 13, 2024)
17-48933268-G-T		SNF8-associated disease • Developmental and epileptic encephalopathy 115	Pathogenic (Dec 07, 2023)
17-48933347-C-G		SNF8-associated disease • Neurodevelopmental disorder plus optic atrophy	Pathogenic (Dec 07, 2023)
17-48936186-C-T		not specified	Uncertain significance (May 29, 2024)
17-48937065-C-T		SNF8-associated disease • Neurodevelopmental disorder plus optic atrophy • not specified	Conflicting classifications of pathogenicity (Jan 30, 2024)
17-48937092-C-T		not specified	Uncertain significance (Oct 30, 2023)
17-48940932-G-A		SNF8-associated disease • Developmental and epileptic encephalopathy 115 • Neurodevelopmental disorder plus optic atrophy	Pathogenic (Dec 07, 2023)
17-48940948-T-A		not specified	Uncertain significance (Apr 23, 2024)
17-48940975-G-A		not specified	Uncertain significance (Mar 04, 2024)
17-48944685-G-A		not specified	Uncertain significance (Jan 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SNF8	protein_coding	protein_coding	ENST00000502492	8	15802

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000457	0.969	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.13	113	152	0.742	0.00000854	1675
Missense in Polyphen		19	40.86	0.465		469
Synonymous	-0.331	66	62.7	1.05	0.00000381	500
Loss of Function	1.91	8	16.3	0.489	8.21e-7	178

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.000435	0.000435
Finnish	0.00	0.00
European (Non-Finnish)	0.0000794	0.0000791
Middle Eastern	0.000435	0.000435
South Asian	0.000163	0.000163
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the endosomal sorting complex required for transport II (ESCRT-II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation by participating in derepression of transcription by RNA polymerase II, possibly via its interaction with ELL. Required for degradation of both endocytosed EGF and EGFR, but not for the EGFR ligand-mediated internalization. It is also required for the degradation of CXCR4. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). {ECO:0000269|PubMed:17714434, ECO:0000269|PubMed:17959629, ECO:0000269|PubMed:18031739, ECO:0000269|PubMed:22660413}.
• Pathway: Endocytosis - Homo sapiens (human);Vesicle-mediated transport;Membrane Trafficking;Endosomal Sorting Complex Required For Transport (ESCRT) (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.380
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.230
• hipred: Y
• hipred_score: 0.831
• ghis: 0.596

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.972

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Snf8
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;positive regulation of gene expression;regulation of multivesicular body size involved in endosome transport;endosomal transport;macroautophagy;endocytic recycling;multivesicular body assembly;regulation of protein catabolic process;protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway;regulation of MAP kinase activity;early endosome to late endosome transport;positive regulation of protein catabolic process;regulation of protein complex stability;multivesicular body sorting pathway;positive regulation of exosomal secretion;regulation of viral budding via host ESCRT complex
• Cellular component: ESCRT II complex;nucleus;nucleoplasm;transcription factor complex;cytoplasm;cytosol;plasma membrane;endosome membrane;membrane;late endosome membrane;perinuclear region of cytoplasm;recycling endosome;extracellular exosome
• Molecular function: protein binding;protein C-terminus binding;transcription factor binding;channel regulator activity;protein homodimerization activity;protein N-terminus binding