MTMR8

protein-coding

myotubularin related protein 8, the group of Myotubularins|Phosphoinositide phosphatases

Gene summary

This gene encodes a member of the myotubularin-related family and is part of the MTMR6 subgroup. Family members are dual-specificity phosphatases and the encoded protein contains a phosphoinositide-binding domain (PID) and a SET-interacting domain (SID). Defects in other family members have been found in myotubular myopathic diseases. [provided by RefSeq, Mar 2010]

MANE transcript

NM_017677.4

Inheritance

—

ClinVar variants

U:162B:17

Top phenotype

MTMR8-related disorder

gnomAD constraint

pLI —, LoF o/e 1.37

Max pathogenic AF

—

Genomic locus

chrX:64,268,081-64,395,452

External References & Databases

Ensembl (ENSG00000102043)

Transcript & Mutation Effects

hg38 • Region Span ~127.4 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 MTMR8 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 102

MTMR8-related disorderTotal: 9

not providedTotal: 8

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Kleine-Levin syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017677.4. 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	Sum
synonymous			6 clinvar	3 clinvar		9
missense			135 clinvar	10 clinvar	3 clinvar	148
nonsense			7 clinvar			7
start loss						0
frameshift			1 clinvar	1 clinvar		2
splice donor/acceptor (+/-2bp)			13 clinvar			13
Total	0	0	162	14	3	179

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017677.4	RefSeq	NP_060147.2	14	MANE Select
ENST00000374852.4	Ensembl	ENSP00000363985.3	14	MANE Select
ENST00001030859.1	Ensembl	ENSP00000700676.1	11	Standard
ENST00001079922.1	Ensembl	ENSP00000749728.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mtmr8	Danio rerio	Structure: slow muscle cell Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

mtmr8

Danio rerio

Structure: slow muscle cell

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inositol phosphate metabolism - Homo sapiens (human)
Phosphatidylinositol signaling system - Homo sapiens (human)
Metabolism of lipids
Metabolism
Synthesis of PIPs at the plasma membrane

Biological Process

phosphatidylinositol biosynthetic process
regulation of autophagy
peptidyl-tyrosine dephosphorylation
phosphatidylinositol dephosphorylation

Molecular Function

phosphatidylinositol-3-phosphatase activity
protein tyrosine phosphatase activity
protein binding
phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity

Cellular Component

nuclear envelope
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374852
Coding exons: 14
Length: 171147
Individuals with no LoFs: 125704
Homozygous LoFs: 10
Heterozygous LoFs: 31
Defined: 125745
p: 0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.34	362	256	1.41	0.0000188	4665
Missense (PolyPhen)		62	53.29	1.1634		1019
Synonymous	-1.59	105	86.2	1.22	0.00000580	1309
Loss of Function	-1.42	24	17.6	1.37	0.00000118	358

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00054	0.00043	rare
Latino/Admixed American	0.000039	0.000029	rare
Ashkenazi Jewish	0.0014	0.00099	notable
East Asian	0.000076	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00022	0.00015	rare
South Asian	0.00026	0.00013	rare
Other	0.00022	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Phosphatase that acts on lipids with a phosphoinositol headgroup. {ECO:0000305}.;

Recessive Scores

pRec: 0.0849

Intolerance Scores

LoFtool: 0.173
RVIS EVS: -0.77
RVIS percentile EVS: 13.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.206

Gene Damage Prediction

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