CAPN10

Summary

CAPN10 (calpain 10, HGNC:1477) is a protein-coding gene on chromosome 2q37.3, encoding Calpain-10 (Q9HC96). Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.

Calpains represent a ubiquitous, well-conserved family of calcium-dependent cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large catalytic subunit has four domains: domain I, the N-terminal regulatory domain that is processed upon calpain activation; domain II, the protease domain; domain III, a linker domain of unknown function; and domain IV, the calmodulin-like calcium-binding domain. This gene encodes a large subunit. It is an atypical calpain in that it lacks the calmodulin-like calcium-binding domain and instead has a divergent C-terminal domain. It is similar in organization to calpains 5 and 6. This gene is associated with type 2 or non-insulin-dependent diabetes mellitus (NIDDM), and is located within the NIDDM1 region. Multiple alternative transcript variants have been described for this gene.

Source: NCBI Gene 11132 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• Clinical variants (ClinVar): 200 total — 5 pathogenic, 2 likely-pathogenic
• MANE Select transcript: NM_023083

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1477
Approved symbol	CAPN10
Name	calpain 10
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000142330
Ensembl biotype	protein_coding
OMIM	605286
Entrez	11132

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 19 protein_coding, 5 nonsense_mediated_decay, 5 retained_intron

ENST00000270361, ENST00000270364, ENST00000352879, ENST00000354082, ENST00000357048, ENST00000391983, ENST00000391984, ENST00000404753, ENST00000416591, ENST00000426297, ENST00000432084, ENST00000463653, ENST00000465943, ENST00000483602, ENST00000493058, ENST00000494738, ENST00000857395, ENST00000857396, ENST00000857397, ENST00000938609, ENST00000938610, ENST00000938611, ENST00000938612, ENST00000938613, ENST00000938614, ENST00000953347, ENST00000953348, ENST00000953349, ENST00000953350

RefSeq mRNA: 2 — MANE Select: NM_023083 NM_023083, NM_023085

CCDS: CCDS33420, CCDS42838

Canonical transcript exons

ENST00000391984 — 12 exons

Exon	Start	End
ENSE00000953555	240589343	240589474
ENSE00000953556	240590815	240591011
ENSE00001811909	240586734	240587052
ENSE00003472026	240597888	240598087
ENSE00003477576	240598651	240599104
ENSE00003515728	240596681	240596942
ENSE00003548365	240593906	240594047
ENSE00003555587	240596319	240596521
ENSE00003634597	240598352	240598397
ENSE00003637410	240591933	240592150
ENSE00003660138	240595024	240595304
ENSE00003663980	240594543	240594709

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 95.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.9345 / max 110.0044, expressed in 1777 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26432	7.9345	1777

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	95.14	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.36	gold quality
granulocyte	CL:0000094	94.32	gold quality
lower esophagus mucosa	UBERON:0035834	94.16	gold quality
cerebellar hemisphere	UBERON:0002245	93.82	gold quality
cerebellar cortex	UBERON:0002129	93.60	gold quality
metanephros cortex	UBERON:0010533	92.59	gold quality
spleen	UBERON:0002106	92.55	gold quality
adenohypophysis	UBERON:0002196	92.31	gold quality
right uterine tube	UBERON:0001302	92.01	gold quality
cerebellum	UBERON:0002037	91.60	gold quality
pituitary gland	UBERON:0000007	91.31	gold quality
right frontal lobe	UBERON:0002810	91.01	gold quality
nerve	UBERON:0001021	90.66	gold quality
tibial nerve	UBERON:0001323	90.66	gold quality
left testis	UBERON:0004533	90.66	gold quality
right testis	UBERON:0004534	90.65	gold quality
right lobe of thyroid gland	UBERON:0001119	90.56	gold quality
body of stomach	UBERON:0001161	90.49	gold quality
right ovary	UBERON:0002118	90.14	gold quality
right adrenal gland cortex	UBERON:0035827	90.11	gold quality
body of uterus	UBERON:0009853	90.10	gold quality
left uterine tube	UBERON:0001303	90.01	gold quality
left adrenal gland cortex	UBERON:0035825	89.96	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.89	gold quality
right adrenal gland	UBERON:0001233	89.80	gold quality
anterior cingulate cortex	UBERON:0009835	89.79	gold quality
mucosa of transverse colon	UBERON:0004991	89.77	gold quality
left lobe of thyroid gland	UBERON:0001120	89.76	gold quality
cingulate cortex	UBERON:0003027	89.76	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RUNX3

miRNA regulators (miRDB)

18 targeting CAPN10, 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-340-5P	100.00	72.50	4437
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-3192-5P	96.98	65.76	1926

Literature-anchored findings (GeneRIF, showing 40)

• type 2 diabetes and three calpain-10 gene polymorphisms in Samoans: no evidence of association (PMID:11704924)
• The variation of calpain-10 gene has impact on the variation of clinical metabolic parameter levels related to type 2 diabetes mellitus. (PMID:11774208)
• polymorphism related to increased serum cholesterol, but not to NIDDM in Japan (PMID:11891023)
• Geographic and haplotype structure of candidate type 2 diabetes susceptibility variants at the calpain-10 locus. (PMID:11891618)
• polymorphism influences glucose metabolism in human fat cells (PMID:11935160)
• Homozygous combination of calpain 10 gene haplotypes is associated with type 2 diabetes mellitus in a Polish population. (PMID:11980626)
• SNP distribution of CAPN10 gene differs in different Chinese nationalities; studied SNPs in CAPN10 gene may not be the major susceptibility ones of NIDDM in Han people of Northern China (PMID:12046551)
• Variation within the type 2 diabetes susceptibility gene calpain-10 and polycystic ovary syndrome. (PMID:12050223)
• No evidence for involvement of the calpain-10 gene ‘high-risk’ haplotype combination for non-insulin-dependent diabetes mellitus in early onset obesity. (PMID:12083814)
• Calpain-10 gene polymorphism is associated with reduced beta(3)-adrenoceptor function in human fat cells. a deletion/insertion polymorphism. (PMID:12107250)
• investigation of the influence of polymorphisms in the Calpain-10 gene on microvascular function (PMID:12107735)
• insulin sensitivity of glucose disposal and lipolysis: no influence of common genetic variants (PMID:12107745)
• The UCSNP44 variation of calpain 10 gene on NIDDM1 locus and its impact on plasma glucose levels in type 2 diabetic patients (PMID:12133483)
• detect the association among calpain-10(CAPN-10) gene polymorphism, hypentension and hyperglycemia (PMID:12137596)
• Variation in gene predisposes to insulin resistance and elevated free fatty acid levels. (PMID:12145185)
• CAPN10 alleles are associated with polycystic ovary syndrome (PMID:12161543)
• Gene frequency of the 112/121 at-risk haplotype of CAPN10 is low among Scandinavians and we were unable to demonstrate significant associations between the CAPN10 variants and type 2 diabetes, insulin resistance, or impaired insulin secretion. (PMID:12453914)
• Genetic variations in the 112/121 haplotype combination defined by the UCSNP-43, -19, and -63 alleles in the calpain-10 gene are not a major factor in the occurrence of type 2 diabetes in Japanese. (PMID:12519860)
• confirmation of role in type 2 diabetes susceptibility (PMID:14574648)
• risk alleles and genotypes, within CAPN10 gene, that could be associated with important phenotypic and prognosis differences observed in polycystic ovary patients. (PMID:14602801)
• “Calpain 10 gene has potential for use in predicting the incidence of type 2 diabetes by genetic diagnosis” p.1766 (PMID:14646187)
• The results suggest that variation in CAPN10 affects risk of type 2 diabetes in the mestizo population of central Mexico (Mexico City and Orizaba) and in Mexican Americans (Starr County, Texas). (PMID:14741193)
• variation at CAPN10 in different human populations over a range of phenotypes related to type 2 diabetes (PMID:14749261)
• calpain-10 has a role in beta-cell survival and is suppressed by RyR2 (PMID:15044459)
• Reduced CAPN10 expression may be risk factor for features associated with metabolic syndrome in obese subjects, although variation in gene does not seem to contribute to risk for developing obesity per se. (PMID:15240652)
• an isoform of calpain-10 is a Ca2+-sensor that functions to trigger exocytosis in pancreatic beta-cells (PMID:15471947)
• We show that the diabetes gene calpain-10 (CAPN10) plays a role in atherosclerosis, insulin sensitivity and insulin secretion in a population enriched for atherosclerosis and insulin resistance. (PMID:15793266)
• Polymorphism of CAPN 10 might be associated with type 2 diabetes. (PMID:15860244)
• Studies confirm calpain 10 expression in cultured muscle cells and support calpains in insulin-stimulated glucose uptake in human skeletal muscle cells that may be relevant to the pathogenesis of the peripheral insulin resistance in type 2 diabetes. (PMID:15862281)
• Calpain 10 is a molecule of importance to insulin signaling and secretion that may have relevance to the future development of novel therapeutic targets for the treatment of T2D[review] (PMID:16028216)
• study provides evidence that messenger RNA expression of calpain-10 (CAPN10) in skeletal muscle is under genetic control and glucose-tolerant individuals upregulate messenger RNA levels in response to prolonged exposure to fat (PMID:16186407)
• There may be one or more relatively common alleles increasing risk of type 2 diabetes in this local region. (PMID:16306378)
• UCSNP-19 of CAPN10 may be involved in the pathogenesis of diabetes in CF. (PMID:16377260)
• Results suggest that a novel 111/121 haplotype combination created by the CAPN10 SNP-43, -19, and -63 increases the susceptibility to the metabolic syndrome in patients with type 2 diabetes. (PMID:16546286)
• A novel diplotype in CAPN10 gene is associated with diabetes mellitus, type 2 in the Korean population. (PMID:16721485)
• SNP-43 of CAPN10 may contribute to the risk of diabetes by regulating abdominal obesity in subjects with high risk of type 2 diabetes. (PMID:16752174)
• the linkage disequilibrium and haplotype diversity studies suggest a role for genetic variation in CAPN10 affecting risk of type 2 diabetes in Europeans. (PMID:16837224)
• No consistent evidence of association of the CAPN10 SNP43 or SNP44 with T2D, obesity, or related quantitative traits, was found. (PMID:16857402)
• Calpain-10 (NIDDM1) as a Susceptibility Gene for Common Type 2 Diabetes. (PMID:16873988)
• the calpain-10 TGA2AGCA haplotype is associated with an increased risk for PCOS. (PMID:17106059)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	capn10	ENSDARG00000076634
mus_musculus	Capn10	ENSMUSG00000026270
rattus_norvegicus	Capn10	ENSRNOG00000045623
caenorhabditis_elegans		WBGENE00000542
caenorhabditis_elegans	clp-3	WBGENE00000544
caenorhabditis_elegans		WBGENE00000546
caenorhabditis_elegans		WBGENE00000547
caenorhabditis_elegans		WBGENE00006606
caenorhabditis_elegans	clp-8	WBGENE00009695
caenorhabditis_elegans	clpr-3	WBGENE00010417
caenorhabditis_elegans	clpr-1	WBGENE00012233
caenorhabditis_elegans	clpr-3	WBGENE00013184

Paralogs (20): CAPN1 (ENSG00000014216), SRI (ENSG00000075142), CAPN6 (ENSG00000077274), CAPN3 (ENSG00000092529), CAPN15 (ENSG00000103326), GCA (ENSG00000115271), ADGB (ENSG00000118492), CAPNS1 (ENSG00000126247), CAPN7 (ENSG00000131375), CAPN9 (ENSG00000135773), CAPN11 (ENSG00000137225), CAPN5 (ENSG00000149260), PEF1 (ENSG00000162517), CAPN2 (ENSG00000162909), CAPN13 (ENSG00000162949), CAPN12 (ENSG00000182472), CAPN8 (ENSG00000203697), CAPN14 (ENSG00000214711), PDCD6 (ENSG00000249915), CAPNS2 (ENSG00000256812)

Protein

Protein identifiers

Calpain-10 — Q9HC96 (reviewed: Q9HC96)

Alternative names: Calcium-activated neutral proteinase 10

All UniProt accessions (4): Q9HC96, B7WPF5, H7C251, H7C2P1

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. May play a role in insulin-stimulated glucose uptake.

Tissue specificity. Detected in primary skeletal muscle cells (at protein level). Ubiquitous.

Disease relevance. Type 2 diabetes mellitus 1 (T2D1) [MIM:601283] A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the peptidase C2 family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q9HC96-1	A, CAPN10a	yes
Q9HC96-2	B, CAPN10b
Q9HC96-3	C, CAPN10c
Q9HC96-4	D, CAPN10d
Q9HC96-5	E, CAPN10e
Q9HC96-6	F, CAPN10f
Q9HC96-7	G, CAPN10g
Q9HC96-8	H, CAPN10h

RefSeq proteins (2): NP_075571, NP_075573 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000169	Pept_cys_AS	Active_site
IPR001300	Peptidase_C2_calpain_cat	Domain
IPR022682	Calpain_domain_III	Domain
IPR022683	Calpain_III	Domain
IPR022684	Calpain_cysteine_protease	Family
IPR033883	C2_III	Domain
IPR036213	Calpain_III_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily

Pfam: PF00648, PF01067

Enzyme classification (BRENDA):

• EC 3.4.22.B30 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (29 total): splice variant 12, sequence variant 8, active site 3, region of interest 2, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HC96-F1	83.91	0.63

Functional residue map

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

Catalytic / active sites (3): 73; 238; 263

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 156 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, GOBP_INSULIN_SECRETION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS

GO Biological Process (9): proteolysis (GO:0006508), cellular component disassembly involved in execution phase of apoptosis (GO:0006921), positive regulation of insulin secretion (GO:0032024), cellular response to insulin stimulus (GO:0032869), regulation of actin cytoskeleton organization (GO:0032956), positive regulation of D-glucose import across plasma membrane (GO:0046326), type B pancreatic cell apoptotic process (GO:0097050), vesicle-mediated transport to the plasma membrane (GO:0098876), positive regulation of type B pancreatic cell apoptotic process (GO:2000676)

GO Molecular Function (7): SNARE binding (GO:0000149), calcium-dependent cysteine-type endopeptidase activity (GO:0004198), cytoskeletal protein binding (GO:0008092), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (4): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
cellular anatomical structure	2
cytoplasm	2
protein metabolic process	1
cellular component disassembly	1
execution phase of apoptosis	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
response to insulin	1
cellular response to peptide hormone stimulus	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
positive regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1
D-glucose import across plasma membrane	1
epithelial cell apoptotic process	1
exocytosis	1
vesicle-mediated transport	1
localization within membrane	1
type B pancreatic cell apoptotic process	1
positive regulation of epithelial cell apoptotic process	1
regulation of type B pancreatic cell apoptotic process	1
cysteine-type endopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1361 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPN10	RNPEPL1	Q9HAU8	889
CAPN10	GPR35	Q9HC97	837
CAPN10	RNPEP	Q9H4A4	763
CAPN10	KCNJ11	Q14654	750
CAPN10	FBN3	Q75N90	690
CAPN10	ENPP1	P22413	680
CAPN10	TCF7L2	Q9NQB0	664
CAPN10	CDKAL1	Q5VV42	607
CAPN10	CAST	P20810	589
CAPN10	SRD5A1	P18405	578
CAPN10	SLC30A8	Q8IWU4	571
CAPN10	SULT2A1	Q06520	553
CAPN10	INSR	P06213	550
CAPN10	CMKLR2	P46091	546
CAPN10	SLC2A4	P14672	543

IntAct

47 interactions, top by confidence:

A	B	Type	Score
FXN	CAPN10	psi-mi:“MI:0915”(physical association)	0.560
CAPN10		psi-mi:“MI:0915”(physical association)	0.560
HSPB1	CAPN10	psi-mi:“MI:0915”(physical association)	0.560
LMNA	CAPN10	psi-mi:“MI:0915”(physical association)	0.560
MAPT	CAPN10	psi-mi:“MI:0915”(physical association)	0.560
	CAPN10	psi-mi:“MI:0915”(physical association)	0.560
LITAF	CAPN10	psi-mi:“MI:0915”(physical association)	0.560
BSCL2	CAPN10	psi-mi:“MI:0915”(physical association)	0.560
HTT	CAPN10	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (30): CAPN10 (Two-hybrid), CAPN10 (Affinity Capture-RNA), CCT2 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), MAP1B (Affinity Capture-MS), TCP1 (Affinity Capture-MS), AHCYL1 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), MAP1A (Affinity Capture-MS), STK3 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), AHCYL2 (Affinity Capture-MS), STK4 (Affinity Capture-MS), CAPN10 (Affinity Capture-MS)

ESM2 similar proteins: A0A061IR73, A0A7N9VSG0, A7YSY2, D3KCC4, D3ZU57, D4A2B7, O08644, O15197, O19179, O43542, O75064, O95382, P0C0K6, P0C0K7, P51840, P52785, P52824, P54777, Q02846, Q05932, Q13470, Q13608, Q1HG60, Q3ZBE0, Q4KM32, Q5JZY3, Q643R3, Q6MG64, Q6NVG1, Q6ZPS2, Q76MJ5, Q7TNJ2, Q80SX8, Q8BYG9, Q8IZY2, Q8NFF5, Q8R5G7, Q8TDZ2, Q8WWN8, Q91V24

Diamond homologs: A6NHC0, A8MX76, G3V7W1, O08529, O08688, O14815, O15484, O23184, O35350, O35646, O35920, O75808, O88456, O88501, P00789, P04574, P04632, P05044, P06813, P06814, P06815, P07384, P13135, P16259, P17655, P20807, P27398, P27730, P28676, P30626, P34308, P35750, P43367, P43368, P51186, P97571, Q07009, Q11002, Q22036, Q27970

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RUNX3	“up-regulates quantity by expression”	CAPN10	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	124
Likely benign	30
Benign	14

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1074535	NM_023083.4(CAPN10):c.1070dup (p.Asn357fs)	Pathogenic
2500179	NM_023083.4(CAPN10):c.1989+1G>A	Pathogenic
562662	GRCh37/hg19 2q37.3(chr2:237480048-241611309)x1	Pathogenic
816588	GRCh37/hg19 2q37.2-37.3(chr2:236172348-241611309)x1	Pathogenic
984989	NM_023083.4(CAPN10):c.837_858dup (p.Ala287fs)	Pathogenic
4533287	NM_023083.4(CAPN10):c.905G>A (p.Trp302Ter)	Likely pathogenic
562672	GRCh37/hg19 2q37.1-37.3(chr2:234716425-242783384)x3	Likely pathogenic

SpliceAI

3112 predictions. Top by Δscore:

Variant	Effect	Δscore
2:240590939:G:GT	donor_gain	1.0000
2:240591931:AG:A	acceptor_gain	1.0000
2:240591932:GG:G	acceptor_gain	1.0000
2:240592147:GCAG:G	donor_gain	1.0000
2:240592148:CAGGT:C	donor_loss	1.0000
2:240592150:GGTGA:G	donor_loss	1.0000
2:240594043:GAGGG:G	donor_gain	1.0000
2:240596477:G:T	donor_gain	1.0000
2:240598079:G:GT	donor_gain	1.0000
2:240598084:ACAGG:A	donor_loss	1.0000
2:240598085:CAG:C	donor_loss	1.0000
2:240598086:AGG:A	donor_loss	1.0000
2:240598087:GG:G	donor_loss	1.0000
2:240598088:GTG:G	donor_loss	1.0000
2:240598089:T:A	donor_loss	1.0000
2:240598350:A:AG	acceptor_gain	1.0000
2:240598351:G:GA	acceptor_loss	1.0000
2:240598351:G:GG	acceptor_gain	1.0000
2:240598351:GGCC:G	acceptor_gain	1.0000
2:240605568:GGG:G	donor_gain	1.0000
2:240605569:GGG:G	donor_gain	1.0000
2:240605571:G:GG	donor_gain	1.0000
2:240587029:G:GT	donor_gain	0.9900
2:240587040:G:GT	donor_gain	0.9900
2:240587049:CCAGG:C	donor_loss	0.9900
2:240587050:CAGGT:C	donor_loss	0.9900
2:240587051:AG:A	donor_loss	0.9900
2:240587052:GG:G	donor_loss	0.9900
2:240587053:GTGG:G	donor_loss	0.9900
2:240587054:T:A	donor_loss	0.9900

AlphaMissense

4324 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:240596446:T:A	V469D	0.996
2:240596451:A:C	S471R	0.996
2:240596453:C:A	S471R	0.996
2:240596453:C:G	S471R	0.996
2:240594646:T:C	F312L	0.995
2:240594648:T:A	F312L	0.995
2:240594648:T:G	F312L	0.995
2:240595107:T:C	F361L	0.995
2:240595109:T:A	F361L	0.995
2:240595109:T:G	F361L	0.995
2:240596481:T:C	F481L	0.995
2:240596483:C:A	F481L	0.995
2:240596483:C:G	F481L	0.995
2:240587038:T:A	W43R	0.994
2:240587038:T:C	W43R	0.994
2:240587040:G:C	W43C	0.993
2:240587040:G:T	W43C	0.993
2:240590997:A:C	E152D	0.993
2:240590997:A:T	E152D	0.993
2:240594613:T:C	F301L	0.993
2:240594615:C:A	F301L	0.993
2:240594615:C:G	F301L	0.993
2:240596482:T:C	F481S	0.993
2:240590996:A:T	E152V	0.992
2:240595299:T:A	W425R	0.992
2:240595299:T:C	W425R	0.992
2:240596457:T:C	F473L	0.992
2:240596459:C:A	F473L	0.992
2:240596459:C:G	F473L	0.992
2:240591008:C:A	A156D	0.990

dbSNP variants (sampled 300 via entrez): RS1000192409 (2:240596646 C>T), RS1000401527 (2:240592127 G>A,T), RS1000432931 (2:240586873 G>A,T), RS1000845295 (2:240593274 T>C), RS1001147367 (2:240592020 C>G,T), RS1001231241 (2:240595799 A>G), RS1001404915 (2:240591058 C>G,T), RS1001460094 (2:240586812 C>A,G,T), RS1001530065 (2:240588322 G>C), RS1001599022 (2:240595545 A>G), RS1001991026 (2:240598975 C>G,T), RS1002022313 (2:240599188 G>A), RS1002348723 (2:240589873 G>A,C), RS1002455242 (2:240584738 G>T), RS1002655732 (2:240594748 C>T)

Disease associations

OMIM: gene MIM:605286 | disease phenotypes: MIM:601283

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (2): diabetes mellitus, noninsulin-dependent, 1 (MONDO:0011027), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C563359	Diabetes Mellitus, Noninsulin-Dependent, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3792269	Efficacy	3	metformin	Diabetes Mellitus
rs5030952	Toxicity	3	tacrolimus	Kidney Transplantation

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3792269	CAPN10	3	3.00	1	metformin
rs5030952	CAPN10	3	2.50	1	tacrolimus

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
pirinixic acid	affects binding, decreases expression, increases activity	1
perfluorooctanoic acid	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
glimepiride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1
Arsenic	affects response to substance	1
Carbamazepine	affects expression	1
Diazinon	increases methylation	1
Diclofenac	affects expression	1
Doxorubicin	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Phthalic Acids	decreases methylation	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Aflatoxin B1	increases expression	1
Zinc Sulfate	decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice