CARD10

Summary

CARD10 (caspase recruitment domain family member 10, HGNC:16422) is a protein-coding gene on chromosome 22q13.1, encoding Caspase recruitment domain-containing protein 10 (Q9BWT7). Scaffold protein that plays an important role in mediating the activation of NF-kappa-B via BCL10 or EGFR.

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]).

Source: NCBI Gene 29775 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 89 and autoimmunity (Limited, GenCC)
• GWAS associations: 17
• Clinical variants (ClinVar): 215 total — 1 pathogenic
• Phenotypes (HPO): 24
• MANE Select transcript: NM_014550

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16422
Approved symbol	CARD10
Name	caspase recruitment domain family member 10
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	CARMA3, BIMP1
Ensembl gene	ENSG00000100065
Ensembl biotype	protein_coding
OMIM	607209
Entrez	29775

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000251973, ENST00000403299, ENST00000406271, ENST00000433485, ENST00000437756, ENST00000467812, ENST00000476871, ENST00000486118, ENST00000488141, ENST00000494166, ENST00000902142, ENST00000902143, ENST00000902144

RefSeq mRNA: 1 — MANE Select: NM_014550 NM_014550

CCDS: CCDS13948

Canonical transcript exons

ENST00000251973 — 20 exons

Exon	Start	End
ENSE00001045522	37506192	37506383
ENSE00001045524	37515973	37516298
ENSE00001045527	37504186	37504301
ENSE00001045529	37518966	37519415
ENSE00001045533	37502602	37502725
ENSE00001045534	37497019	37497178
ENSE00001045535	37504635	37504769
ENSE00001045544	37496449	37496560
ENSE00001045553	37517971	37518108
ENSE00001045554	37503185	37503213
ENSE00003548534	37510212	37510421
ENSE00003562262	37494086	37494188
ENSE00003576488	37495517	37495586
ENSE00003588618	37490362	37491393
ENSE00003604516	37492644	37492802
ENSE00003619407	37495760	37496003
ENSE00003630688	37491755	37491867
ENSE00003631420	37507829	37507954
ENSE00003636124	37508527	37508682
ENSE00003691913	37492435	37492550

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 96.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.0907 / max 64.9138, expressed in 1102 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194066	2.2706	928
194067	0.6604	380
194065	0.1597	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	96.01	gold quality
jejunal mucosa	UBERON:0000399	95.77	gold quality
pancreatic ductal cell	CL:0002079	94.65	gold quality
sural nerve	UBERON:0015488	94.62	gold quality
duodenum	UBERON:0002114	93.26	gold quality
renal glomerulus	UBERON:0000074	92.82	gold quality
apex of heart	UBERON:0002098	92.80	gold quality
metanephric glomerulus	UBERON:0004736	92.40	gold quality
mucosa of transverse colon	UBERON:0004991	92.14	gold quality
ileal mucosa	UBERON:0000331	91.62	gold quality
nephron tubule	UBERON:0001231	89.59	gold quality
gingival epithelium	UBERON:0001949	89.44	gold quality
small intestine	UBERON:0002108	89.15	gold quality
right testis	UBERON:0004534	89.04	gold quality
kidney epithelium	UBERON:0004819	89.03	gold quality
left testis	UBERON:0004533	89.01	gold quality
right lobe of liver	UBERON:0001114	88.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.63	gold quality
colonic mucosa	UBERON:0000317	87.90	gold quality
epithelial cell of pancreas	CL:0000083	87.57	gold quality
gingiva	UBERON:0001828	87.57	gold quality
visceral pleura	UBERON:0002401	87.38	gold quality
testis	UBERON:0000473	87.29	gold quality
endothelial cell	CL:0000115	87.17	gold quality
jejunum	UBERON:0002115	87.09	gold quality
cortex of kidney	UBERON:0001225	87.02	gold quality
transverse colon	UBERON:0001157	86.83	gold quality
metanephros	UBERON:0000081	86.63	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.32	gold quality
adult mammalian kidney	UBERON:0000082	86.22	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.53

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

50 targeting CARD10, 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-574-5P	100.00	66.01	989
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-371A-3P	99.99	66.77	91
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-4685-5P	99.25	65.99	1563

Literature-anchored findings (GeneRIF, showing 35)

• CARMA1 and CARMA3 bind to Ikappa kinase gamma-NFkappaB in B and T lymphocytes (PMID:15184390)
• CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in hepatocytes. (PMID:17101977)
• Protein kinase C-CARMA3 signaling axis plays an essential role in lysophosphatidic acid-induced ovarian cancer cell in vitro invasion. (PMID:17724468)
• results further define the molecular mechanisms that control activation of NF-kappaB and reveal a function for A20 in the regulation of CARMA and BCL10 activity in lymphoid and non-lymphoid cells (PMID:18349075)
• Data demonstrate that lysophosphatidic acid stimulates thymic stromal lymphopoietin and CCL20 expression in bronchial epithelial cells via CARMA3-mediated NF-kappaB activation. (PMID:18757306)
• components of the CBM complex, Carma3, Bcl10, and Malt1 are key mediators of the CXCL8/IL8-induced NFkappaB activation and VEGF up-regulation. (PMID:19112107)
• activation of NF-kappaB by CXCR4 occurs through Carma3/Bcl10/Malt1 (CBM) complex in OSCC. loss of components of CBM complex in HNSCC can inhibit SDF-1 alpha induced phosphorylation and degradation of IkappaBalpha. (PMID:20695076)
• Polymorphisms of ATOH7, TGFBR3 and CARD10 influence the size of optic disc area. (PMID:21307088)
• Data show that CARMA3 and Bcl10 contributed to several characteristics of EGFR-associated malignancy, including proliferation, survival, migration, and invasion. (PMID:21406399)
• The overexpression of CARMA3 was significantly correlated with TNM stage (P = 0.022) and tumor status (P = 0.013). (PMID:22615840)
• this study found that CARMA3 is overexpressed in colon cancers and contributes to malignant cell growth by facilitating cell cycle progression through NF-kappaB mediated upregulation of cyclin D1. (PMID:22884800)
• miR-146a expression is up-regulated in a majority of gastric cancers where it targets CARD10 and COPS8, inhibiting GPCR-mediated activation of NF-kappaB. (PMID:22992343)
• Genetic variation within PARP1 and CARD10 was associated with rate of hippocampal neurodegeneration in APOE e3/e3 patients. (PMID:23608917)
• CARMA3 facilitates proliferation and inhibits apoptosis through nuclear factor-kappaB signaling. (PMID:23708960)
• Data show that CARMA3 may serve as a novel and prognostic marker for renal cell carcinoma (RCC) and play a role during the development and progression of the disease. (PMID:23771851)
• overexpression of CARMA3 in human glioma and its correlation with tumor grade. (PMID:23893382)
• CARD10 may be involved in hepatic carcinogenesis associated with hepatitis C in Egyptian patients. (PMID:24018495)
• CARMA3 is overexpressed in bladder cancer and regulates malignant cell growth and NF-kappaB signaling. (PMID:24443255)
• CARMA3 is overexpressed in pancreatic cancer and regulates malignant cell growth, invasion, and NF-kappaB signaling, which was dependent on its association with Bcl10. (PMID:24633921)
• CARMA3 regulates the ovarian cancer cell proliferation, cell cycle progression, and chemoresistance. (PMID:24833094)
• The study identified the DEP domain-containing protein DEPDC7 as cellular binding partner of CARMA2 and CARMA3 proteins. (PMID:25541973)
• A novel mechanism of CARMA3 in lung cancer stemness and metastasis through the negative regulation of NME2 was identified. (PMID:25906011)
• Findings indicate that CARMA3 may suppress the activation of the P38 MAPK signaling pathway to regulate invasion, migration and apoptosis of lung cancer cells by activating NF-small ka, CyrillicB (P65) in the nucleus. (PMID:26526492)
• Data indicate no association between caspase recruitment domain family, member 10 protein (CARD10) polymorphism rs6000782 and type 1 autoimmune hepatitis (AIH) in a Japanese population. (PMID:26652023)
• Card10 polymorphisms may not be linked with psoriasis vulgaris in the southern Han Chinese population. (PMID:28301668)
• The results suggest that the involvement of CARMA3 in DNA damage-induced NF-kappaB is through the recruitment of TRAF6. (PMID:28717989)
• High CARMA3 expression is associated with Breast Cancer. (PMID:29259013)
• Card10 is expressed in granulocytes and is a direct target of CEBPE with functions extending to myeloid differentiation. (PMID:29773596)
• The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer. (PMID:30723269)
• Caspase recruitment domain family member 10 regulates carbamoyl phosphate synthase 1 and promotes cancer growth in bladder cancer cells. (PMID:31565867)
• Higher expression of CARMA3 in hepatocellular carcinoma (HCC) was relevant to poor prognostic survival. Down-regulation of CARMA3 inhibited proliferation and colony formation and induced apoptosis in HCC cell lines, while increasing its expression promoted tumorigenesis. (PMID:31576094)
• CARD10 promotes the progression of renal cell carcinoma by regulating the NFkappaB signaling pathway. (PMID:31939627)
• Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity. (PMID:32238915)
• CARMA3 Transcriptional Regulation of STMN1 by NF-kappaB Promotes Renal Cell Carcinoma Proliferation and Invasion. (PMID:34190011)
• CARMA3: A potential therapeutic target in non-cancer diseases. (PMID:36618379)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000111638
mus_musculus	Card10	ENSMUSG00000033170
rattus_norvegicus	Card10	ENSRNOG00000008401

Paralogs (3): CARD14 (ENSG00000141527), CARD9 (ENSG00000187796), CARD11 (ENSG00000198286)

Protein

Protein identifiers

Caspase recruitment domain-containing protein 10 — Q9BWT7 (reviewed: Q9BWT7)

Alternative names: CARD-containing MAGUK protein 3

All UniProt accessions (3): Q9BWT7, B0QYC3, B0QYC4

UniProt curated annotations — full annotation on UniProt →

Function. Scaffold protein that plays an important role in mediating the activation of NF-kappa-B via BCL10 or EGFR.

Subunit / interactions. CARD10 and BCL10 bind to each other by CARD-CARD interaction. They both participate in a complex with MALT1, where MALT1 binds to BCL10. Interacts with TMEM43; this interaction is essential for EGFR-mediated NF-kappa-B activation.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in adult heart, kidney and liver; lower levels in intestine, placenta, muscle and lung. Also found in fetal lung, liver and kidney.

Disease relevance. Immunodeficiency 89 and autoimmunity (IMD89) [MIM:619632] An autosomal recessive disorder characterized by adult onset of recurrent infections, allergies, microcytic anemia, and Crohn disease. The disease may be caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BWT7-1	1	yes
Q9BWT7-2	2

RefSeq proteins (1): NP_055365* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001315	CARD	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR042140	CARD_CARD10	Domain

Pfam: PF00619

UniProt features (14 total): region of interest 3, splice variant 2, sequence variant 2, compositionally biased region 2, chain 1, domain 1, sequence conflict 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWT7-F1	70.22	0.32

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): 18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 267 (showing top): MORF_RAGE, MODULE_52, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_PHOSPHORYLATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_NEGATIVE_REGULATION_OF_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, MODULE_45, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GOBP_ACTIVATION_OF_NF_KAPPAB_INDUCING_KINASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, MODULE_16, RAMJAUN_APOPTOSIS_BY_TGFB1_VIA_MAPK1_UP, MODULE_118

GO Biological Process (8): activation of NF-kappaB-inducing kinase activity (GO:0007250), regulation of apoptotic process (GO:0042981), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), regulation of immune response (GO:0050776), protein-containing complex assembly (GO:0065003), negative regulation of cell migration involved in sprouting angiogenesis (GO:0090051), positive regulation of protein localization to nucleus (GO:1900182), positive regulation of macromolecule metabolic process (GO:0010604)

GO Molecular Function (2): signaling receptor complex adaptor activity (GO:0030159), protein binding (GO:0005515)

GO Cellular Component (3): immunological synapse (GO:0001772), cytoplasm (GO:0005737), CBM complex (GO:0032449)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
activation of protein kinase activity	1
non-canonical NF-kappaB signal transduction	1
apoptotic process	1
regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
regulation of immune system process	1
immune response	1
regulation of response to stimulus	1
cellular component assembly	1
protein-containing complex organization	1
cell migration involved in sprouting angiogenesis	1
negative regulation of blood vessel endothelial cell migration	1
regulation of cell migration involved in sprouting angiogenesis	1
protein localization to nucleus	1
regulation of protein localization to nucleus	1
positive regulation of protein localization	1
positive regulation of metabolic process	1
macromolecule metabolic process	1
regulation of macromolecule metabolic process	1
signaling receptor binding	1
signaling adaptor activity	1
binding	1
plasma membrane	1
intracellular anatomical structure	1
intracellular protein-containing complex	1

Protein interactions and networks

STRING

1782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CARD10	BCL10	O95999	998
CARD10	MALT1	Q9UDY8	996
CARD10	IKBKG	Q9Y6K9	850
CARD10	TMEM43	Q9BTV4	632
CARD10	IKBKB	O14920	632
CARD10	CARD14	Q9BXL6	591
CARD10	NFKB1	P19838	583
CARD10	AGTR1	P30556	557
CARD10	CARD6	Q9BX69	541
CARD10	PRKCQ	Q04759	515
CARD10	CCND1	P24385	511
CARD10	CARD11	Q9BXL7	497
CARD10	ARRB2	P32121	490
CARD10	NOD2	Q9HC29	487
CARD10	NOD1	Q9Y239	486

IntAct

334 interactions, top by confidence:

A	B	Type	Score
PRPF18	CARD10	psi-mi:“MI:0915”(physical association)	0.560
CARD10	CHIC2	psi-mi:“MI:0915”(physical association)	0.560
JOSD1	CARD10	psi-mi:“MI:0915”(physical association)	0.560
CWF19L2	CARD10	psi-mi:“MI:0915”(physical association)	0.560
FAM47B	CARD10	psi-mi:“MI:0915”(physical association)	0.560
CARD10	ZNF223	psi-mi:“MI:0915”(physical association)	0.560
KRT75	CARD10	psi-mi:“MI:0915”(physical association)	0.560
CCDC116	CARD10	psi-mi:“MI:0915”(physical association)	0.560
ZNF587	CARD10	psi-mi:“MI:0915”(physical association)	0.560
CARD10	ZNF552	psi-mi:“MI:0915”(physical association)	0.560
FOXD4L3	CARD10	psi-mi:“MI:0915”(physical association)	0.560
CARD10	GSTP1	psi-mi:“MI:0915”(physical association)	0.560
PNKP	CARD10	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	CARD10	psi-mi:“MI:0915”(physical association)	0.560
CARD10	ZNF180	psi-mi:“MI:0915”(physical association)	0.560
ZNF32	CARD10	psi-mi:“MI:0915”(physical association)	0.560
CARD10	CBX8	psi-mi:“MI:0915”(physical association)	0.560
ZSCAN25	CARD10	psi-mi:“MI:0915”(physical association)	0.560
CARD10	ZNF581	psi-mi:“MI:0915”(physical association)	0.560
ZNF80	CARD10	psi-mi:“MI:0915”(physical association)	0.560
ZNF202	CARD10	psi-mi:“MI:0915”(physical association)	0.560
UTP14C	CARD10	psi-mi:“MI:0915”(physical association)	0.560
ZNF564	CARD10	psi-mi:“MI:0915”(physical association)	0.560
ZNF10	CARD10	psi-mi:“MI:0915”(physical association)	0.560
BCL6B	CARD10	psi-mi:“MI:0915”(physical association)	0.560
ZNF775	CARD10	psi-mi:“MI:0915”(physical association)	0.560
CARD10	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.560
CARD10	ZBTB26	psi-mi:“MI:0915”(physical association)	0.560
ZNF329	CARD10	psi-mi:“MI:0915”(physical association)	0.560
ZNF575	CARD10	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (149): KLHL12 (Two-hybrid), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS), CARD10 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIT1, A0A1B0GVG4, A0JNH6, A1A5D9, A6NC98, A6NGB0, A6NJZ7, A6NNM3, F6XLV1, O15049, O54887, P0C7N4, P58660, P60531, Q0D2H9, Q0P5D1, Q2KJ21, Q2TAC2, Q3LUD3, Q3T1I3, Q3TMW1, Q3V0F0, Q4QRL3, Q5JTB6, Q5RD60, Q66HR5, Q6NSJ2, Q6PHN1, Q6QZQ4, Q80VM7, Q8BP01, Q8C7U1, Q8CB62, Q8CGU1, Q8CHW5, Q8K2I2, Q8N137, Q8N283, Q8N6Y0, Q8R370

Diamond homologs: A2AIV8, P58660, Q8CIS0, Q99KF0, Q9BWT7, Q9BXL6, Q9BXL7, Q9EPY0, Q9H257

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TBKBP1	“up-regulates activity”	CARD10	relocalization
CARD10	“up-regulates activity”	PRKCQ	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	156
Likely benign	17
Benign	21

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1326845	NM_014550.4(CARD10):c.1258C>T (p.Arg420Cys)	Pathogenic

SpliceAI

3586 predictions. Top by Δscore:

Variant	Effect	Δscore
22:37491749:CCTCA:C	donor_loss	1.0000
22:37491750:CTCA:C	donor_loss	1.0000
22:37491751:TCA:T	donor_loss	1.0000
22:37491761:T:TA	donor_gain	1.0000
22:37491762:C:A	donor_gain	1.0000
22:37492639:CTCAC:C	donor_loss	1.0000
22:37492640:TCACC:T	donor_loss	1.0000
22:37492641:CA:C	donor_loss	1.0000
22:37492642:A:AG	donor_loss	1.0000
22:37492642:AC:A	donor_gain	1.0000
22:37492643:CC:C	donor_gain	1.0000
22:37492643:CCCG:C	donor_gain	1.0000
22:37492798:CGGCT:C	acceptor_gain	1.0000
22:37492799:GGCT:G	acceptor_gain	1.0000
22:37492801:CT:C	acceptor_gain	1.0000
22:37492803:C:CC	acceptor_gain	1.0000
22:37492803:CT:C	acceptor_loss	1.0000
22:37492805:G:C	acceptor_gain	1.0000
22:37492809:C:CT	acceptor_gain	1.0000
22:37492810:A:T	acceptor_gain	1.0000
22:37492820:C:CT	acceptor_gain	1.0000
22:37494083:CA:C	donor_loss	1.0000
22:37494084:A:AC	donor_gain	1.0000
22:37494085:C:A	donor_loss	1.0000
22:37494085:C:CC	donor_gain	1.0000
22:37494085:CCTG:C	donor_gain	1.0000
22:37494184:TTCAG:T	acceptor_gain	1.0000
22:37494185:TCAG:T	acceptor_gain	1.0000
22:37494186:CAG:C	acceptor_gain	1.0000
22:37494186:CAGC:C	acceptor_gain	1.0000

AlphaMissense

6584 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:37492661:A:G	F873S	0.999
22:37506383:C:G	A398P	0.999
22:37507836:C:G	R395P	0.999
22:37516265:A:G	L136S	0.999
22:37516267:G:C	F135L	0.999
22:37516267:G:T	F135L	0.999
22:37516268:A:G	F135S	0.999
22:37516269:A:G	F135L	0.999
22:37518057:A:G	F96S	0.999
22:37518090:A:C	L85W	0.999
22:37518090:A:G	L85S	0.999
22:37518096:T:A	D83V	0.999
22:37518102:A:G	L81P	0.999
22:37519049:A:G	L51P	0.999
22:37519049:A:T	L51Q	0.999
22:37519053:A:C	Y50D	0.999
22:37519117:C:A	W28C	0.999
22:37519117:C:G	W28C	0.999
22:37491797:A:T	V941D	0.998
22:37492691:A:G	L863P	0.998
22:37504223:G:T	R533S	0.998
22:37506316:C:G	R420P	0.998
22:37506337:A:G	L413P	0.998
22:37506370:C:G	R402P	0.998
22:37507881:C:G	R380P	0.998
22:37517976:A:G	I123T	0.998
22:37518039:A:G	F102S	0.998
22:37518045:A:G	L100P	0.998
22:37518069:C:T	G92D	0.998
22:37518070:C:G	G92R	0.998

dbSNP variants (sampled 300 via entrez): RS1000038688 (22:37492800 G>A), RS1000114339 (22:37518500 A>G), RS1000135902 (22:37502660 G>T), RS1000235696 (22:37515132 G>C), RS1000257818 (22:37496323 G>A,C), RS1000304694 (22:37503901 T>C), RS1000440270 (22:37502443 C>A,T), RS1000691733 (22:37496663 A>G), RS1000736083 (22:37520404 G>A), RS1000782838 (22:37491024 T>G), RS1000870171 (22:37499634 C>A,T), RS1000908927 (22:37505365 T>C), RS1001040429 (22:37494196 G>A), RS1001063700 (22:37491993 G>A), RS1001092461 (22:37493854 C>T)

Disease associations

OMIM: gene MIM:607209 | disease phenotypes: MIM:619632, MIM:137760

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 89 and autoimmunity	Limited	Unknown

Mondo (2): immunodeficiency 89 and autoimmunity (MONDO:0030484), OPTN-related open angle glaucoma (MONDO:0100553)

Orphanet (0):

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002099	Asthma
HP:0002110	Bronchiectasis
HP:0002783	Recurrent lower respiratory tract infections
HP:0002923	Rheumatoid factor positive
HP:0003212	Increased circulating IgE concentration
HP:0003237	Increased circulating IgG concentration
HP:0003261	Increased circulating IgA concentration
HP:0003493	Antinuclear antibody positivity
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0003621	Juvenile onset
HP:0004840	Hypochromic microcytic anemia
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0031891	Decreased total eosinophil count
HP:0031944	Pleural thickening
HP:0032069	Anti-thyroglobulin antibody positivity
HP:0032446	Pulmonary bulla
HP:0034163	Reduced circulating interleukin 10 concentration
HP:0034165	Reduced circulating interleukin 21 concentration
HP:0034168	Reduced circulating interleukin 22 concentration
HP:0034171	Reduced circulating interleukin 23 concentration
HP:0034174	Reduced circulating interleukin 27 concentration
HP:0034177	Reduced circulating interleukin 17A concentration
HP:0100280	Crohn’s disease

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000970_2	Optic disc area	3.000000e-12
GCST000970_4	Optic disc area	1.000000e-08
GCST002423_1	Autoimmune hepatitis type-1	3.000000e-06
GCST002626_18	Vertical cup-disc ratio	8.000000e-09
GCST002763_10	Optic disc area	2.000000e-13
GCST002763_18	Optic disc area	2.000000e-06
GCST002763_19	Optic disc area	7.000000e-09
GCST003210_9	Low vWF levels	8.000000e-07
GCST004075_24	Vertical cup-disc ratio	4.000000e-08
GCST004075_25	Vertical cup-disc ratio	3.000000e-12
GCST004076_11	Optic disc area	2.000000e-10
GCST004076_25	Optic disc area	4.000000e-17
GCST009411_5	Optic disc area	4.000000e-11
GCST009462_5	Optic disc size	3.000000e-24
GCST009723_12	Vertical cup-disc ratio (adjusted for vertical disc diameter)	3.000000e-15
GCST009724_106	Vertical cup-disc ratio (multi-trait analysis)	3.000000e-20
GCST010002_82	Refractive error	2.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006939	cup-to-disc ratio measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, increases expression, decreases expression	4
Valproic Acid	affects expression, increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Tetrachlorodibenzodioxin	increases expression	3
bisphenol A	increases expression	2
Arsenic	increases expression, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Lipopolysaccharides	affects reaction, increases localization, decreases expression, affects response to substance, increases expression	2
Genistein	increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
2-anisidine	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
rutecarpine	increases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
belinostat	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
eprenetapopt	increases expression, affects reaction	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	decreases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Cadmium	increases abundance, decreases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7LP	Ubigene A-549 CARD10 KO	Cancer cell line	Male
CVCL_D8IF	Ubigene HCT 116 CARD10 KO	Cancer cell line	Male
CVCL_D9B0	Ubigene HEK293 CARD10 KO	Transformed cell line	Female
CVCL_D9ZC	Ubigene HeLa CARD10 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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