CARMIL2

capping protein regulator and myosin 1 linker 2

Basic information

Region (hg38): 16:67644987-67657569

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 58	AR	Allergy/Immunology/Infectious; Oncologic	Individuals 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 management	Allergy/Immunology/Infectious; Dermatologic; Oncologic; Pulmonary	27647349; 27896283; 28112205; 29479355

ClinVar

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

• not provided (746 variants)
• Severe combined immunodeficiency due to CARMIL2 deficiency (29 variants)
• Inborn genetic diseases (11 variants)
• CARMIL2-related condition (9 variants)
• not specified (8 variants)
• Combined immunodeficiency;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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	176	7	188
missense	1	3	335	11	9	359
nonsense	10	3	1			14
start loss						0
frameshift	10	4	1			15
inframe indel			5		1	6
splice donor/acceptor (+/-2bp)		9			1	10
splice region			22	29	3	54
non coding			5	102	23	130
Total	21	19	352	289	41

Highest pathogenic variant AF is 0.0000461

Variants in CARMIL2

This is a list of pathogenic ClinVar variants found in the CARMIL2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-67645252-C-T			Likely benign (Dec 01, 2022)
16-67645256-A-C		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
16-67645261-C-G			Likely benign (Jul 11, 2022)
16-67645261-C-T			Likely benign (Nov 22, 2023)
16-67645262-G-A			Uncertain significance (Mar 12, 2022)
16-67645264-C-A			Uncertain significance (Aug 20, 2022)
16-67645264-C-T			Likely benign (Jan 09, 2023)
16-67645274-T-G			Uncertain significance (Jun 20, 2022)
16-67645280-C-T			Uncertain significance (Aug 10, 2022)
16-67645281-T-C			Uncertain significance (Feb 01, 2022)
16-67645283-C-T			Pathogenic (Feb 10, 2022)
16-67645298-C-G			Likely benign (Dec 27, 2023)
16-67645299-C-T			Likely benign (Jan 06, 2024)
16-67645303-C-T			Likely benign (Feb 22, 2023)
16-67645445-C-T		not specified	Benign (Jan 24, 2024)
16-67645535-C-G			Uncertain significance (Apr 16, 2022)
16-67645541-C-T			Uncertain significance (Nov 02, 2022)
16-67645553-G-A			Likely benign (Apr 04, 2023)
16-67645592-C-T			Likely benign (Jun 01, 2022)
16-67645596-C-T			Likely benign (May 04, 2022)
16-67645602-G-C			Uncertain significance (Aug 21, 2022)
16-67645604-G-A			Likely benign (Jan 25, 2024)
16-67645607-G-C			Uncertain significance (Oct 13, 2023)
16-67645614-G-A			Uncertain significance (Feb 22, 2022)
16-67645621-A-G			Uncertain significance (Feb 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CARMIL2	protein_coding	protein_coding	ENST00000334583	38	12651

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.93e-11	1.00	124971	0	56	125027	0.000224

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.57	703	831	0.846	0.0000522	9032
Missense in Polyphen		179	236.34	0.7574		2931
Synonymous	0.774	346	365	0.948	0.0000242	3095
Loss of Function	4.81	32	77.8	0.411	0.00000445	803

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000645	0.000600
Ashkenazi Jewish	0.0000996	0.0000993
East Asian	0.000294	0.000274
Finnish	0.0000929	0.0000926
European (Non-Finnish)	0.000286	0.000256
Middle Eastern	0.000294	0.000274
South Asian	0.000236	0.000229
Other	0.000172	0.000165

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

• 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_gene_trap: N

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