CARD19

Summary

CARD19 (caspase recruitment domain family member 19, HGNC:28148) is a protein-coding gene on chromosome 9q22.31, encoding Caspase recruitment domain-containing protein 19 (Q96LW7). Plays a role in inhibiting the effects of BCL10-induced activation of NF-kappa-B.

Predicted to enable CARD domain binding activity. Predicted to be involved in negative regulation of canonical NF-kappaB signal transduction. Located in mitochondrion.

Source: NCBI Gene 84270 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total
• Druggable target: yes
• MANE Select transcript: NM_032310

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28148
Approved symbol	CARD19
Name	caspase recruitment domain family member 19
Location	9q22.31
Locus type	gene with protein product
Status	Approved
Aliases	MGC11115, bA370F5.1, BinCARD
Ensembl gene	ENSG00000165233
Ensembl biotype	protein_coding
OMIM	617726
Entrez	84270

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding_CDS_not_defined, 5 protein_coding, 1 nonsense_mediated_decay

ENST00000375464, ENST00000466409, ENST00000466929, ENST00000468781, ENST00000475574, ENST00000488630, ENST00000490488, ENST00000495641, ENST00000498243, ENST00000870801, ENST00000870802, ENST00000870803, ENST00000917508

RefSeq mRNA: 3 — MANE Select: NM_032310 NM_001318010, NM_001318011, NM_032310

CCDS: CCDS6702

Canonical transcript exons

ENST00000375464 — 6 exons

Exon	Start	End
ENSE00003541623	93112218	93112289
ENSE00003561855	93110568	93110721
ENSE00003577493	93107674	93107816
ENSE00003644133	93112992	93113283
ENSE00003646666	93111879	93111938
ENSE00003847191	93096217	93096352

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 97.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.9799 / max 318.5008, expressed in 1811 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97386	20.3069	1809
97385	1.0956	687
97387	0.5774	307

Top tissues by expression

256 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.22	gold quality
leukocyte	CL:0000738	96.80	gold quality
pancreatic ductal cell	CL:0002079	96.07	silver quality
granulocyte	CL:0000094	95.84	gold quality
right coronary artery	UBERON:0001625	95.83	gold quality
ascending aorta	UBERON:0001496	95.67	gold quality
thoracic aorta	UBERON:0001515	95.65	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.46	gold quality
aorta	UBERON:0000947	95.43	gold quality
popliteal artery	UBERON:0002250	95.34	gold quality
tibial artery	UBERON:0007610	95.34	gold quality
descending thoracic aorta	UBERON:0002345	95.30	gold quality
cerebellar hemisphere	UBERON:0002245	95.24	gold quality
cerebellar cortex	UBERON:0002129	95.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.74	gold quality
left uterine tube	UBERON:0001303	94.67	gold quality
cerebellum	UBERON:0002037	94.63	gold quality
nasal cavity epithelium	UBERON:0005384	94.62	gold quality
endocervix	UBERON:0000458	94.61	gold quality
left coronary artery	UBERON:0001626	94.55	gold quality
mucosa of stomach	UBERON:0001199	94.42	gold quality
left testis	UBERON:0004533	94.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.18	gold quality
coronary artery	UBERON:0001621	94.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.16	gold quality
right testis	UBERON:0004534	94.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.93	gold quality
lower esophagus	UBERON:0013473	93.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.71	gold quality
spinal cord	UBERON:0002240	93.62	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	34.43
E-ANND-3	yes	7.84
E-HCAD-1	yes	5.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting CARD19, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-1238-5P	94.82	67.52	493
HSA-MIR-4758-5P	94.82	67.06	499

Literature-anchored findings (GeneRIF, showing 4)

• BinCard inhibits BCL10-mediated activation of NF-kappa B. (PMID:15637807)
• the crystal structure of BinCARD reveals that all three cysteines were oxidized (PMID:23633586)
• BinCARD isoform2 (BinCARD2) is a one of CARD proteins involved in apoptosis and inflammation. BinCARD2 knock down suppresses innate immune responses induced by 3pRNA, poly(I:C) and vesicular stomatitis virus (VSV). (PMID:30795865)
• CARD19, the protein formerly known as BinCARD, is a mitochondrial protein that does not regulate Bcl10-dependent NF-kappaB activation after TCR engagement. (PMID:32763502)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Card19	ENSMUSG00000037960
rattus_norvegicus	Card19	ENSRNOG00000016560

Protein

Protein identifiers

Caspase recruitment domain-containing protein 19 — Q96LW7 (reviewed: Q96LW7)

Alternative names: Bcl10-interacting CARD protein

All UniProt accessions (1): Q96LW7

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in inhibiting the effects of BCL10-induced activation of NF-kappa-B. May inhibit the phosphorylation of BCL10 in a CARD-dependent manner.

Subunit / interactions. Associates with BCL10 by CARD-CARD interaction.

Subcellular location. Nucleus Endoplasmic reticulum membrane. Mitochondrion membrane.

Tissue specificity. Expressed in ovary, testis, placenta, skeletal muscle, kidney, lung, heart and liver (at protein level). Expressed in thymus and brain.

Miscellaneous. Appears to be the dominant isoform in peripheral blood cell fractions. Contains a transmembrane helix.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96LW7-1	1	yes
Q96LW7-2	2

RefSeq proteins (3): NP_001304939, NP_001304940, NP_115686* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR042146	CARD_BinCARD	Domain
IPR043574	CARD19	Family

UniProt features (15 total): helix 7, mutagenesis site 2, chain 1, domain 1, modified residue 1, disulfide bond 1, splice variant 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4FH0	X-RAY DIFFRACTION	1.4
4DWN	X-RAY DIFFRACTION	1.58

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LW7-F1	64.51	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 113

Disulfide bonds (1): 7–77

Mutagenesis-validated functional residues (2):

Position	Phenotype
17	abolishes the nf-kappa-b inhibitory activity.
65	abolishes the nf-kappa-b inhibitory activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 129 (showing top): BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, MODULE_151, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_NEGATIVE_REGULATION_OF_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, chr9q22, GOBP_PROTEIN_CATABOLIC_PROCESS, MODULE_114, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_DN, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK

GO Biological Process (1): negative regulation of canonical NF-kappaB signal transduction (GO:0043124)

GO Molecular Function (1): CARD domain binding (GO:0050700)

GO Cellular Component (7): nucleus (GO:0005634), mitochondrion (GO:0005739), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), mitochondrial membrane (GO:0031966), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	3
cytoplasm	3
organelle membrane	2
cellular anatomical structure	2
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
protein domain specific binding	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
mitochondrion	1
mitochondrial envelope	1
endomembrane system	1

Protein interactions and networks

STRING

366 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CARD19	BCL10	O95999	586
CARD19	CCDC85A	Q96PX6	480
CARD19	ABTB1	Q969K4	474
CARD19	MEGF8	Q7Z7M0	452
CARD19	MINDY3	Q9H8M7	447
CARD19	BUD13	Q9BRD0	445
CARD19	CARD14	Q9BXL6	438
CARD19	ASB5	Q8WWX0	431
CARD19	PCYOX1	Q9UHG3	426
CARD19	ZNF221	Q9UK13	418
CARD19	CRADD	P78560	414
CARD19	EPN3	Q9H201	411
CARD19	BRAT1	Q6PJG6	403
CARD19	SLC9C2	Q5TAH2	401
CARD19	NUP43	Q8NFH3	382

IntAct

31 interactions, top by confidence:

A	B	Type	Score
EXOC6	EXOC5	psi-mi:“MI:0914”(association)	0.840
BCL10	CARD19	psi-mi:“MI:0915”(physical association)	0.600
CARD19	BCL10	psi-mi:“MI:0915”(physical association)	0.600
BCL10	CARD19	psi-mi:“MI:0403”(colocalization)	0.600
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
TRAK2	OGT	psi-mi:“MI:0914”(association)	0.530
FAM3B	LRP5	psi-mi:“MI:0914”(association)	0.530
APOOL	MTX2	psi-mi:“MI:0914”(association)	0.530
TRAK1	MTX2	psi-mi:“MI:0914”(association)	0.530
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
CUL4A	DDX39A	psi-mi:“MI:0914”(association)	0.350
FAXC	METTL15	psi-mi:“MI:0914”(association)	0.350
MGARP	RTL8C	psi-mi:“MI:0914”(association)	0.350
TMEM169	GPR89A	psi-mi:“MI:0914”(association)	0.350
MTX2	EXOC5	psi-mi:“MI:0914”(association)	0.350
CD244	CAND2	psi-mi:“MI:0914”(association)	0.350
TRAK1	PEX14	psi-mi:“MI:0914”(association)	0.350
PCNP	PAPSS2	psi-mi:“MI:0914”(association)	0.350
HDDC3	CLTCL1	psi-mi:“MI:0914”(association)	0.350
CRACR2B	CARD19	psi-mi:“MI:0914”(association)	0.350
FAXC	POLRMT	psi-mi:“MI:0914”(association)	0.350
CHCHD3	EXOC5	psi-mi:“MI:0914”(association)	0.350
MTX2	ACTB	psi-mi:“MI:0914”(association)	0.350
MTCH2	IPO5	psi-mi:“MI:0914”(association)	0.350
CD244	VGF	psi-mi:“MI:0914”(association)	0.350
MTX2	RP2	psi-mi:“MI:0914”(association)	0.350
UBR2	NIPSNAP2	psi-mi:“MI:0914”(association)	0.350
SLC35B2	NDUFS8	psi-mi:“MI:0914”(association)	0.350

BioGRID (43): C9orf89 (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), BCL10 (Reconstituted Complex), C9orf89 (Affinity Capture-MS), C9orf89 (Affinity Capture-MS), BCL10 (Two-hybrid)

ESM2 similar proteins: A1YEX3, A2AGX3, A6QPH9, A7YWH3, E9Q6D6, O35618, O95999, P0DM64, P0DMS9, P24278, Q071E0, Q0JJE3, Q1A5X6, Q2HJ21, Q495C1, Q4KLN5, Q4V7B1, Q562E2, Q5EG05, Q5RDW3, Q5RFR2, Q5SXH7, Q5VT97, Q5VUJ9, Q5XIN1, Q68D85, Q68UT4, Q6P2K3, Q6PIF2, Q80TL0, Q8BSV3, Q8CDF7, Q8IZS7, Q8N2C3, Q8N7W2, Q8N8I0, Q8NCT3, Q8NFN8, Q8NFT6, Q8NHP7

Diamond homologs: Q58D91, Q96LW7, Q9D1I2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

46 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1013 predictions. Top by Δscore:

Variant	Effect	Δscore
9:93107672:A:AG	acceptor_gain	1.0000
9:93107672:A:G	acceptor_loss	1.0000
9:93107673:G:GA	acceptor_loss	1.0000
9:93107673:G:GG	acceptor_gain	1.0000
9:93107805:G:GT	donor_gain	1.0000
9:93107824:GGAG:G	donor_gain	1.0000
9:93107825:G:GT	donor_gain	1.0000
9:93107827:GG:G	donor_loss	1.0000
9:93107829:T:A	donor_loss	1.0000
9:93107834:G:T	donor_gain	1.0000
9:93110566:A:AG	acceptor_gain	1.0000
9:93110567:G:GA	acceptor_gain	1.0000
9:93110567:GTTCC:G	acceptor_gain	1.0000
9:93110717:TCTGC:T	donor_gain	1.0000
9:93110718:CTGC:C	donor_gain	1.0000
9:93110718:CTGCG:C	donor_loss	1.0000
9:93110719:TGCG:T	donor_loss	1.0000
9:93110720:GC:G	donor_gain	1.0000
9:93110721:CG:C	donor_loss	1.0000
9:93110722:G:GG	donor_gain	1.0000
9:93110723:T:A	donor_loss	1.0000
9:93111926:C:G	donor_gain	1.0000
9:93111930:G:GG	donor_gain	1.0000
9:93112990:A:AG	acceptor_gain	1.0000
9:93112991:G:GG	acceptor_gain	1.0000
9:93096351:AGG:A	donor_loss	0.9900
9:93096353:GTGG:G	donor_loss	0.9900
9:93096354:T:A	donor_loss	0.9900
9:93107673:GATC:G	acceptor_gain	0.9900
9:93107673:GATCA:G	acceptor_gain	0.9900

AlphaMissense

1174 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:93110656:T:C	F80S	0.999
9:93107703:G:C	D13H	0.998
9:93107704:A:T	D13V	0.998
9:93107770:T:C	L35P	0.998
9:93110568:T:C	F51L	0.998
9:93110569:T:C	F51S	0.998
9:93110570:C:A	F51L	0.998
9:93110570:C:G	F51L	0.998
9:93110611:T:C	L65P	0.998
9:93110655:T:C	F80L	0.998
9:93110657:C:A	F80L	0.998
9:93110657:C:G	F80L	0.998
9:93107704:A:C	D13A	0.997
9:93107734:T:C	L23S	0.997
9:93107776:G:C	R37P	0.997
9:93107794:T:A	L43H	0.997
9:93107794:T:C	L43P	0.997
9:93110623:T:C	L69P	0.997
9:93110662:G:C	R82P	0.997
9:93110668:T:C	L84P	0.997
9:93107695:T:C	L10P	0.996
9:93107703:G:T	D13Y	0.996
9:93107712:T:C	F16L	0.996
9:93107714:C:A	F16L	0.996
9:93107714:C:G	F16L	0.996
9:93107716:T:C	L17P	0.996
9:93107752:A:T	D29V	0.996
9:93107758:T:C	I31T	0.996
9:93107764:T:C	L33P	0.996
9:93107808:G:C	A48P	0.996

dbSNP variants (sampled 300 via entrez): RS1000044111 (9:93094774 G>A,C), RS1000057693 (9:93100725 C>T), RS1000109637 (9:93100946 A>G), RS1000331921 (9:93094986 G>A,C), RS1000389585 (9:93099710 T>C), RS1000459645 (9:93099308 T>C), RS1000876545 (9:93107587 C>A,G), RS1001029093 (9:93112757 G>A), RS1001393844 (9:93100929 T>C), RS1001542827 (9:93112435 G>A), RS1001725603 (9:93107176 C>T), RS1001779346 (9:93112916 C>G,T), RS1001839516 (9:93095345 C>T), RS1001879978 (9:93113596 C>T), RS1002163736 (9:93101386 T>A)

Disease associations

OMIM: gene MIM:617726 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008863_2	Malate levels	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010508	malate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067439 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.48	Kd	329.3	nM	CHEMBL3752910
6.48	ED50	329.3	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149836: Binding affinity to human C9orf89 incubated for 45 mins by Kinobead based pull down assay	kd	0.3293	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	7
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
entinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	1
Atrazine	increases expression	1
Cisplatin	increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652878	Binding	Binding affinity to human C9orf89 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.