MTMR14

protein-coding

myotubularin related protein 14, the group of Myotubularins|Phosphoinositide phosphatases

Gene summary

This gene encodes a myotubularin-related protein. The encoded protein is a phosphoinositide phosphatase that specifically dephosphorylates phosphatidylinositol 3,5-biphosphate and phosphatidylinositol 3-phosphate. Mutations in this gene are correlated with autosomal dominant centronuclear myopathy. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 18.[provided by RefSeq, Apr 2010]

Previous symbols:

C3orf29

MANE transcript

NM_001077525.3

Inheritance

ClinVar variants

P:1U:206B:81

Top phenotype

MTMR14-related disorder

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr3:9,649,433-9,702,393

External References & Databases

Ensembl (ENSG00000163719)

Transcript & Mutation Effects

hg38 • Region Span ~53.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal dominant centronuclear myopathyMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0008048

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MTMR14 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 315

not specifiedTotal: 87

MTMR14-related disorderTotal: 13

Autosomal dominant centronuclear myopathyTotal: 10

MYOPATHY, CENTRONUCLEAR, AUTOSOMAL DOMINANT, MODIFIER OFTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001077525.3. 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			9 clinvar	67 clinvar	5 clinvar	81
missense			180 clinvar	7 clinvar	1 clinvar	188
nonsense		1 clinvar	3 clinvar			4
start loss						0
frameshift			5 clinvar	1 clinvar		6
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	1	206	75	6	288

Highest pathogenic variant AF is 0.000042411084

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 153 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001077525.3	RefSeq	NP_001070993.1	19	MANE Select
ENST00000296003.9	Ensembl	ENSP00000296003.5	19	MANE Select
NM_001077526.3	RefSeq	NP_001070994.1	18	Standard
NM_001400518.1	RefSeq	NP_001387447.1	20	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mtmr14	Danio rerio	Structure: post-vent region Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

mtmr14

Danio rerio

Structure: post-vent region

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inositol phosphate metabolism - Homo sapiens (human)
Autophagy - animal - Homo sapiens (human)
Phosphatidylinositol signaling system - Homo sapiens (human)
Metabolism of lipids
3-phosphoinositide degradation

Biological Process

phosphatidylinositol biosynthetic process
macroautophagy
peptidyl-tyrosine dephosphorylation

Molecular Function

phosphatidylinositol-3-phosphatase activity
protein serine/threonine phosphatase activity
protein tyrosine phosphatase activity
protein binding
phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity

Cellular Component

ruffle
cytosol
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296003
Coding exons: 19
Length: 52961
Individuals with no LoFs: 124704
Homozygous LoFs: 1
Heterozygous LoFs: 129
Defined: 124834
p: 0.000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.298	352	368	0.956	0.0000231	4226
Missense (PolyPhen)		198	217.46	0.9105		2576
Synonymous	-2.18	183	149	1.23	0.00000898	1282
Loss of Function	3.08	18	38.6	0.466	0.00000210	433

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.00089	0.00089	rare
East Asian	0.0016	0.0016	notable
Finnish	0.000099	0.000093	rare
European (Non-Finnish)	0.00056	0.00056	rare
South Asian	0.00049	0.00049	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Lipid phosphatase which efficiently dephosphorylates phosphatidylinositol 3-phosphate (PtdIns3P) and PtdIns(3,5)P2; inactive toward PtdIns4P, PtdIns(3,4)P2, PtdIns(4,5)P2 and PtdIns(3,4,5)P3. {ECO:0000269|PubMed:17008356}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.119
RVIS EVS: -0.91
RVIS percentile EVS: 9.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0943

Gene Damage Prediction

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