CARD10

protein-coding

caspase recruitment domain family member 10, the group of Caspase recruitment domain containing|Membrane associated guanylate kinases

Gene summary

The caspase recruitment domain (CARD) is a protein module that consists of 6 or 7 antiparallel alpha helices. It participates in apoptosis signaling through highly specific protein-protein homophilic interactions. Like several other CARD proteins, CARD10 belongs to the membrane-associated guanylate kinase (MAGUK) family and activates NF-kappa-B (NFKB; see MIM 164011) through BCL10 (MIM 603517) (Wang et al., 2001 [PubMed 11259443]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_014550.4

Inheritance

ClinVar variants

P:1U:171B:25

Top phenotype

Immunodeficiency 89 and autoimmunity

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr22:37,490,362-37,519,542

External References & Databases

Ensembl (ENSG00000100065)

Transcript & Mutation Effects

hg38 • Region Span ~29.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency 89 and autoimmunityLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030484

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Immunodeficiency 89 and autoimmunityAR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: The condition may involve susceptibility to infections (including involving pulmonary sequelae), and and prophylactic measures, as well as early and aggressive treatment of infections may be beneficial

Refs: 32238915

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CARD10 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 168

CARD10-related disorderTotal: 21

not providedTotal: 9

Primary open angle glaucomaTotal: 5

Immunodeficiency 89 and autoimmunityTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014550.4. 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			2 clinvar	12 clinvar	5 clinvar	19
missense		1 clinvar	161 clinvar	4 clinvar	4 clinvar	170
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	1	171	16	9	197

Highest pathogenic variant AF is 0.0000013720056

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014550.4	RefSeq	NP_055365.2	20	MANE Select
ENST00000251973.10	Ensembl	ENSP00000251973.5	20	MANE Select
ENST00000403299.5	Ensembl	ENSP00000384570.1	20	Standard
ENST00000403299.6	Ensembl	ENSP00000384570.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NF-kappa B signaling pathway - Homo sapiens (human)

Biological Process

activation of NF-kappaB-inducing kinase activity
regulation of apoptotic process
protein-containing complex assembly
negative regulation of cell migration involved in sprouting angiogenesis
positive regulation of protein localization to nucleus

Molecular Function

protein binding
receptor signaling complex scaffold activity

Cellular Component

cytoplasm
CBM complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000403299
Coding exons: 20
Length: 29150
Individuals with no LoFs: 125685
Homozygous LoFs: 0
Heterozygous LoFs: 63
Defined: 125748
p: 0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.20	465	619	0.751	0.0000408	6427
Missense (PolyPhen)		78	124.16	0.6282		1235
Synonymous	0.604	250	262	0.953	0.0000153	2174
Loss of Function	4.71	15	51.4	0.292	0.00000259	571

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00052	0.00049	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000049	0.000046	rare
European (Non-Finnish)	0.00031	0.00030	rare
South Asian	0.00020	0.00020	rare
Other	0.00068	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates NF-kappa-B via BCL10 and IKK.;

Recessive Scores

pRec: 0.0937

Intolerance Scores

LoFtool: 0.659
RVIS EVS: -1.15
RVIS percentile EVS: 6.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.911

Gene Damage Prediction

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