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
neurodevelopmental disorder plus optic atrophy (Moderate), 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.

not_specified (21 variants)
SNF8-associated_disease (7 variants)
Neurodevelopmental_disorder_plus_optic_atrophy (4 variants)
Developmental_and_epileptic_encephalopathy_115 (4 variants)
SNF8-associated_disorder (2 variants)
Aganglionic_megacolon (1 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. These statistics are base on transcript: NM_000007241.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous						0
missense	4 clinvar	1 clinvar	21 clinvar			26
nonsense	1 clinvar					1
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	7	1	21	0	0

Highest pathogenic variant AF is 0.00016912633

Loading clinvar variants...

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