MKLN1

protein-coding

muskelin 1, the group of CTLH complex

Gene summary

Muskelin is an intracellular protein that acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component thrombospondin I (MIM 188060) (Adams et al., 1998 [PubMed 9724633]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_013255.5

Inheritance

—

ClinVar variants

U:58

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr7:131,110,096-131,496,632

External References & Databases

Ensembl (ENSG00000128585)

Transcript & Mutation Effects

hg38 • Region Span ~386.5 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 MKLN1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 46

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013255.5. 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			2 clinvar			2
missense			51 clinvar			51
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	58	0	0	58

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013255.5	RefSeq	NP_037387.2	18	MANE Select
ENST00000352689.11	Ensembl	ENSP00000323527.6	18	MANE Select
NM_001145354.2	RefSeq	NP_001138826.1	18	Standard
NM_001321316.2	RefSeq	NP_001308245.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of receptor internalization
cell-matrix adhesion
signal transduction
regulation of cell shape
actin cytoskeleton reorganization

Molecular Function

protein homodimerization activity

Cellular Component

ubiquitin ligase complex
ruffle
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000352689
Coding exons: 18
Length: 386541
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125736
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.74	232	383	0.606	0.0000185	4913
Missense (PolyPhen)		32	116.4	0.27492		1506
Synonymous	1.50	111	133	0.834	0.00000649	1269
Loss of Function	5.75	3	44.2	0.0678	0.00000225	534

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (PubMed:29911972). Required for internalization of the GABA receptor GABRA1 from the cell membrane via endosomes and subsequent GABRA1 degradation (By similarity). Acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component THBS1 (PubMed:18710924). {ECO:0000250|UniProtKB:O89050, ECO:0000269|PubMed:18710924, ECO:0000269|PubMed:29911972}.;

Recessive Scores

pRec: 0.146

Intolerance Scores

LoFtool: 0.224
RVIS EVS: -0.43
RVIS percentile EVS: 25.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.940

Gene Damage Prediction

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