MARCHF8

protein-coding

membrane associated ring-CH-type finger 8, the group of Ring finger proteins|Membrane associated ring-CH-type fingers

Gene summary

MARCH8 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH8 induces the internalization of several membrane glycoproteins (Goto et al., 2003 [PubMed 12582153]; Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Apr 2010]

Previous symbols:

MIR
MARCH8

MANE transcript

NM_001282866.2

Inheritance

—

ClinVar variants

—

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr10:45,454,585-45,594,906

External References & Databases

Ensembl (ENSG00000165406)

Transcript & Mutation Effects

hg38 • Region Span ~140.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MARCHF8 variants in ClinVar

0 Conditions Cataloged

No annotated ClinVar phenotypes.

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001282866.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB
synonymous
missense
nonsense
start loss
frameshift
splice donor/acceptor (+/-2bp)
Total	0	0	0	0	0

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001282866.2	RefSeq	NP_001269795.1	7	MANE Select
ENST00000453424.7	Ensembl	ENSP00000411848.2	7	MANE Select
NM_001002266.3	RefSeq	NP_001002266.1	6	Standard
NM_001401645.1	RefSeq	NP_001388574.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
march8	Danio rerio	Structure: whole organism Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

march8

Danio rerio

Structure: whole organism

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein polyubiquitination
adaptive immune response

Molecular Function

ubiquitin-protein transferase activity
zinc ion binding

Cellular Component

lysosome
lysosomal membrane
endosome
integral component of membrane
cytoplasmic vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395771
Coding exons: 6
Length: 140320
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.04	124	161	0.770	0.00000861	1921
Missense (PolyPhen)		31	44.908	0.6903		530
Synonymous	0.746	56	63.6	0.881	0.00000401	531
Loss of Function	0.708	11	13.8	0.795	5.83e-7	181

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00013	0.000099	rare
East Asian	0.00017	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.000068	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of CD86 and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. May also promote ubiquitination and endocytosis of TFRC and FAS. {ECO:0000269|PubMed:12582153, ECO:0000269|PubMed:14722266, ECO:0000269|PubMed:18389477, ECO:0000269|PubMed:19117940, ECO:0000269|PubMed:19566897}.;

Recessive Scores

pRec: 0.100

Intolerance Scores

LoFtool: 0.845
RVIS EVS: 0.68
RVIS percentile EVS: 85.04

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.707

Gene Damage Prediction

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