GeneBe

CARMIL2

capping protein regulator and myosin 1 linker 2

Basic information

Region (hg38): 16:67644988-67657569

Previous symbols: [ "RLTPR" ]

Links

ENSG00000159753 ∙ NCBI:146206 ∙ OMIM:610859 ∙ HGNC:27089 ∙ Uniprot:Q6F5E8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • severe combined immunodeficiency due to CARMIL2 deficiency (Moderate), mode of inheritance: AR
  • severe combined immunodeficiency due to CARMIL2 deficiency (Strong), mode of inheritance: AR
  • severe combined immunodeficiency due to CARMIL2 deficiency (Supportive), mode of inheritance: AR
  • severe combined immunodeficiency due to CARMIL2 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Immunodeficiency 58ARAllergy/Immunology/Infectious; OncologicIndividuals may have severe and frequent infections, and prophylactic measures, as well as early and aggressive treatment of infections may be beneficial; Individuals may be at increased risk of certain types of neoplasms, and awareness may allow prompt diagnosis and managementAllergy/Immunology/Infectious; Dermatologic; Oncologic; Pulmonary27647349; 27896283; 28112205; 29479355

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CARMIL2 gene.

  • not_provided (1043 variants)
  • Severe_combined_immunodeficiency_due_to_CARMIL2_deficiency (38 variants)
  • CARMIL2-related_disorder (37 variants)
  • Inborn_genetic_diseases (11 variants)
  • Combined_immunodeficiency (3 variants)
  • not_specified (2 variants)
  • Autosomal_recessive_congenital_ichthyosis (1 variants)
  • Chronic_colitis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CARMIL2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001013838.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
7
clinvar
286
clinvar
8
clinvar
 301
missense
2
clinvar
5
clinvar
401
clinvar
16
clinvar
7
clinvar
 431
nonsense
19
clinvar
3
clinvar
2
clinvar
 24
start loss
0
frameshift
23
clinvar
5
clinvar
1
clinvar
 29
splice donor/acceptor (+/-2bp)
1
clinvar
11
clinvar
1
clinvar
 13
Total 45 24 411 302 16

Highest pathogenic variant AF is 0.0000487285

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CARMIL2protein_codingprotein_codingENST00000334583 3812651
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
2.93e-111.001249710561250270.000224
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.577038310.8460.00005229032
Missense in Polyphen179236.340.75742931
Synonymous0.7743463650.9480.00002423095
Loss of Function4.813277.80.4110.00000445803

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0006450.000600
Ashkenazi Jewish0.00009960.0000993
East Asian0.0002940.000274
Finnish0.00009290.0000926
European (Non-Finnish)0.0002860.000256
Middle Eastern0.0002940.000274
South Asian0.0002360.000229
Other0.0001720.000165

dbNSFP

Source: dbNSFP

Function
FUNCTION: Cell membrane-cytoskeleton-associated protein that plays a role in the regulation of actin polymerization at the barbed end of actin filaments. Prevents F-actin heterodimeric capping protein (CP) activity at the leading edges of migrating cells, and hence generates uncapped barbed ends and enhances actin polymerization (PubMed:26466680). Plays a role in cell protrusion formations; involved in cell polarity, lamellipodial assembly, membrane ruffling and macropinosome formations (PubMed:19846667, PubMed:26578515, PubMed:26466680). Involved as well in cell migration and invadopodia formation during wound healing (PubMed:19846667, PubMed:26578515, PubMed:26466680). {ECO:0000269|PubMed:19846667, ECO:0000269|PubMed:26466680, ECO:0000269|PubMed:26578515}.;

Recessive Scores

pRec
0.0922

Intolerance Scores

loftool
rvis_EVS
-1.12
rvis_percentile_EVS
6.61

Haploinsufficiency Scores

pHI
0.228
hipred
N
hipred_score
0.429
ghis
0.614

Essentials

essential_gene_CRISPR
essential_gene_CRISPR2
essential_gene_gene_trap
N
gene_indispensability_pred
gene_indispensability_score

Mouse Genome Informatics

Gene name
Carmil2
Phenotype
behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; pigmentation phenotype; vision/eye phenotype; immune system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process
establishment or maintenance of cell polarity;positive regulation of lamellipodium assembly;maintenance of cell polarity;positive regulation of cell migration;wound healing, spreading of cells;actin filament network formation;establishment or maintenance of monopolar cell polarity;positive regulation of extracellular matrix disassembly;positive regulation of ruffle assembly;positive regulation of lamellipodium organization;negative regulation of barbed-end actin filament capping
Cellular component
ruffle;cytoplasm;plasma membrane;actin cytoskeleton;membrane;lamellipodium;extrinsic component of cytoplasmic side of plasma membrane;cell leading edge;macropinosome;intermediate filament cytoskeleton
Molecular function
phospholipid binding;protein-containing complex binding