MYLIP

protein-coding

myosin regulatory light chain interacting protein, the group of MicroRNA protein coding host genes|Ring finger proteins|FERM domain containing

Gene summary

The ERM protein family members ezrin, radixin, and moesin are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. Myosin regulatory light chain interacting protein (MYLIP) is a novel ERM-like protein that interacts with myosin regulatory light chain and inhibits neurite outgrowth. [provided by RefSeq, Jul 2008]

MANE transcript

NM_013262.4

Inheritance

—

ClinVar variants

U:94B:33

Top phenotype

MYLIP-related disorder

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr6:16,129,086-16,151,367

External References & Databases

Ensembl (ENSG00000007944)

Transcript & Mutation Effects

hg38 • Region Span ~22.3 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 MYLIP variants in ClinVar

4 Conditions Cataloged

not providedTotal: 86

not specifiedTotal: 59

MYLIP-related disorderTotal: 1

Inherited lipid metabolism disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013262.4. 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			1 clinvar	25 clinvar	2 clinvar	28
missense			89 clinvar	5 clinvar	1 clinvar	95
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	94	30	3	127

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013262.4	RefSeq	NP_037394.2	7	MANE Select
ENST00000356840.8	Ensembl	ENSP00000349298.3	7	MANE Select
NM_001436627.1	RefSeq	NP_001423556.1	6	Standard
ENST00000349606.4	Ensembl	ENSP00000008686.5	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cholesterol metabolism - Homo sapiens (human)
miR-targeted genes in epithelium - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
Immune System

Biological Process

protein polyubiquitination
ubiquitin-dependent protein catabolic process
nervous system development
negative regulation of neuron projection development
negative regulation of low-density lipoprotein particle clearance

Molecular Function

ubiquitin-protein transferase activity
protein binding
cytoskeletal protein binding
metal ion binding
ubiquitin protein ligase activity

Cellular Component

cytosol
cytoskeleton
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356840
Coding exons: 7
Length: 19124
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.08	205	253	0.809	0.0000138	2923
Missense (PolyPhen)		42	74.891	0.56081		859
Synonymous	0.0306	105	105	0.996	0.00000634	849
Loss of Function	3.06	5	19.6	0.255	9.17e-7	246

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol- dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR. {ECO:0000269|PubMed:10593918, ECO:0000269|PubMed:12826659, ECO:0000269|PubMed:14550572, ECO:0000269|PubMed:19520913, ECO:0000269|PubMed:20427281, ECO:0000269|PubMed:22109552}.;

Recessive Scores

pRec: 0.152

Intolerance Scores

LoFtool: 0.232
RVIS EVS: 0.35
RVIS percentile EVS: 74.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.964

Gene Damage Prediction

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