MARCKSL1

protein-coding

MARCKS like 1

Gene summary

This gene encodes a member of the myristoylated alanine-rich C-kinase substrate (MARCKS) family. Members of this family play a role in cytoskeletal regulation, protein kinase C signaling and calmodulin signaling. The encoded protein affects the formation of adherens junction. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are located on the long arm of chromosomes 6 and 10. [provided by RefSeq, Jun 2012]

Previous symbols:

MANE transcript

NM_023009.7

Inheritance

—

ClinVar variants

U:30B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr1:32,333,839-32,336,233

External References & Databases

Ensembl (ENSG00000175130)

Transcript & Mutation Effects

hg38 • Region Span ~2.4 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 MARCKSL1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 29

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_023009.7. 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	1 clinvar	1 clinvar	3
missense			29 clinvar			29
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	30	1	1	32

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_023009.7	RefSeq	NP_075385.1	2	MANE Select
ENST00000329421.8	Ensembl	ENSP00000362638.4	2	MANE Select
ENST00000853128.1	Ensembl	ENSP00000523187.1	2	Standard
ENST00000853128.2	Ensembl	ENSP00000523187.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
marcksl1b	Danio rerio	Structure: retinal ganglion cell Quality: aplastic/hypoplastic abnormal

Gene / Model

Organism

Observed Phenotype

marcksl1b

Danio rerio

Structure: retinal ganglion cell

Quality: aplastic/hypoplastic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fc gamma R-mediated phagocytosis - Homo sapiens (human)
Leishmaniasis - Homo sapiens (human)

Biological Process

positive regulation of cell population proliferation

Molecular Function

actin binding
protein binding
calmodulin binding

Cellular Component

cytoplasm
cytoskeleton
plasma membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000329421
Coding exons: 2
Length: 2548
Individuals with no LoFs: 125692
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125697
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.186	107	102	1.05	0.00000489	1252
Missense (PolyPhen)		26	22.339	1.1639		253
Synonymous	-0.733	48	42.0	1.14	0.00000220	400
Loss of Function	0.614	3	4.39	0.684	1.83e-7	74

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000037	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Controls cell movement by regulating actin cytoskeleton homeostasis and filopodium and lamellipodium formation (PubMed:22751924). When unphosphorylated, induces cell migration (By similarity). When phosphorylated by MAPK8, induces actin bundles formation and stabilization, thereby reducing actin plasticity, hence restricting cell movement, including neuronal migration (By similarity). May be involved in coupling the protein kinase C and calmodulin signal transduction systems (By similarity). {ECO:0000250|UniProtKB:P28667, ECO:0000269|PubMed:22751924}.;

Recessive Scores

pRec: 0.178

Intolerance Scores

LoFtool: 0.409
RVIS EVS: -0.27
RVIS percentile EVS: 33.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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