MARCHF6

membrane associated ring-CH-type finger 6, the group of Membrane associated ring-CH-type fingers|Ring finger proteins

Basic information

Region (hg38): 5:10353695-10440388

Previous symbols: [ "MARCH6" ]

Links

ENSG00000145495

∙ NCBI:10299 ∙ OMIM:613297 ∙ HGNC:30550 ∙ Uniprot:O60337 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

benign adult familial myoclonic epilepsy (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, familial adult myoclonic, 3	AD	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	14978679; 20548044; 31664039

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MARCHF6 gene.

not_specified (74 variants)
Epilepsy,_familial_adult_myoclonic,_3 (5 variants)
not_provided (3 variants)
MARCHF6-related_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MARCHF6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005885.4. 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			2 clinvar			2
missense			77 clinvar	1 clinvar		78
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	80	1	0

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MARCHF6	protein_coding	protein_coding	ENST00000274140	26	86686

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.16e-7	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.88	263	509	0.517	0.0000277	5889
Missense in Polyphen		44	164.74	0.26708		1979
Synonymous	0.612	176	187	0.943	0.0000105	1818
Loss of Function	6.71	4	60.2	0.0664	0.00000343	638

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000103	0.000103
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000601	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000267	0.0000264
Middle Eastern	0.0000601	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase that promotes ubiquitination of DIO2, leading to its degradation. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. May cooperate with UBE2G1. {ECO:0000269|PubMed:15673284, ECO:0000269|PubMed:19651899}.;
Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);ER Quality Control Compartment (ERQC);Calnexin/calreticulin cycle;Post-translational protein modification;Metabolism of proteins;Asparagine N-linked glycosylation;N-glycan trimming in the ER and Calnexin/Calreticulin cycle (Consensus)

Recessive Scores

pRec: 0.139

Intolerance Scores

loftool: 0.207
rvis_EVS: -0.56
rvis_percentile_EVS: 19.54

Haploinsufficiency Scores

pHI: 0.278
hipred: Y
hipred_score: 0.783
ghis: 0.608

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: K
gene_indispensability_pred: E
gene_indispensability_score: 0.641

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: March6
Phenotype

Gene ontology

Biological process: proteasomal protein catabolic process;ubiquitin-dependent ERAD pathway;ERAD pathway;protein K48-linked ubiquitination;endoplasmic reticulum mannose trimming
Cellular component: ER ubiquitin ligase complex;endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of membrane;integral component of endoplasmic reticulum membrane;endoplasmic reticulum quality control compartment
Molecular function: ubiquitin-protein transferase activity;protein binding;zinc ion binding;enzyme binding;ubiquitin conjugating enzyme binding;ubiquitin protein ligase activity;ubiquitin-specific protease binding