CAPN11

Summary

CAPN11 (calpain 11, HGNC:1478) is a protein-coding gene on chromosome 6p21.1, encoding Calpain-11 (Q9UMQ6). Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.

Calpains constitute a family of intracellular calcium-dependent cysteine proteases. There are eight members in this superfamily. They consist of a variable 80 kDa subunit and an invariant 30 kDa subunit. This calpain protein appears to have protease activity and calcium-binding ability. A similar mouse protein may play a functional role in spermatogenesis and in the regulation of calcium-dependent signal transduction events during meiosis.

Source: NCBI Gene 11131 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 119 total
• MANE Select transcript: NM_007058

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1478
Approved symbol	CAPN11
Name	calpain 11
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137225
Ensembl biotype	protein_coding
OMIM	604822
Entrez	11131

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000398776, ENST00000524554, ENST00000526118, ENST00000532171, ENST00000533604

RefSeq mRNA: 1 — MANE Select: NM_007058 NM_007058

CCDS: CCDS47436

Canonical transcript exons

ENST00000398776 — 23 exons

Exon	Start	End
ENSE00000929782	44169906	44169975
ENSE00000929783	44172302	44172420
ENSE00000929784	44172940	44173073
ENSE00000929785	44173218	44173386
ENSE00000929786	44176068	44176151
ENSE00000929787	44176253	44176338
ENSE00000929788	44176581	44176655
ENSE00000929793	44183119	44183235
ENSE00000974659	44182941	44183019
ENSE00001085447	44183705	44183763
ENSE00001279211	44183906	44184401
ENSE00002142858	44158820	44158864
ENSE00003505274	44180933	44180997
ENSE00003535566	44169281	44169531
ENSE00003566510	44177242	44177420
ENSE00003576577	44180748	44180805
ENSE00003577138	44166758	44166829
ENSE00003586800	44176838	44176998
ENSE00003606290	44180597	44180662
ENSE00003615410	44180460	44180499
ENSE00003619823	44179619	44179630
ENSE00003663401	44179952	44180163
ENSE00003688367	44181252	44181320

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 90.76.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2342 / max 144.7983, expressed in 44 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67976	0.1212	4
67978	0.0984	36
67977	0.0105	2
204005	0.0041	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	90.76	gold quality
right testis	UBERON:0004534	89.89	gold quality
testis	UBERON:0000473	87.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.98	gold quality
omental fat pad	UBERON:0010414	72.37	gold quality
peritoneum	UBERON:0002358	72.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.09	gold quality
adipose tissue of abdominal region	UBERON:0007808	71.60	gold quality
subcutaneous adipose tissue	UBERON:0002190	70.82	gold quality
tibial nerve	UBERON:0001323	69.97	gold quality
adipose tissue	UBERON:0001013	68.08	gold quality
sural nerve	UBERON:0015488	67.16	gold quality
connective tissue	UBERON:0002384	66.82	gold quality
ectocervix	UBERON:0012249	66.60	gold quality
right coronary artery	UBERON:0001625	66.00	gold quality
skin of abdomen	UBERON:0001416	65.71	gold quality
adult organism	UBERON:0007023	65.47	gold quality
skin of leg	UBERON:0001511	64.59	gold quality
right adrenal gland cortex	UBERON:0035827	64.39	gold quality
right adrenal gland	UBERON:0001233	64.36	gold quality
vena cava	UBERON:0004087	62.91	gold quality
zone of skin	UBERON:0000014	62.70	gold quality
coronary artery	UBERON:0001621	62.46	gold quality
left coronary artery	UBERON:0001626	62.42	gold quality
body of uterus	UBERON:0009853	62.21	gold quality
minor salivary gland	UBERON:0001830	61.66	gold quality
gall bladder	UBERON:0002110	61.64	gold quality
lower esophagus muscularis layer	UBERON:0035833	61.13	gold quality
lower esophagus	UBERON:0013473	61.10	gold quality
vagina	UBERON:0000996	61.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting CAPN11, 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-2110	99.96	66.68	1930
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-3194-5P	96.80	64.90	1027

Literature-anchored findings (GeneRIF, showing 1)

• Characterization of a related mouse gene and comparison of the protein to the human protein. (PMID:16541461)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	capn1a	ENSDARG00000052702
danio_rerio	capn1b	ENSDARG00000052748
mus_musculus	Capn11	ENSMUSG00000058626
rattus_norvegicus	Capn11	ENSRNOG00000026025
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), CAPN10 (ENSG00000142330), CAPN5 (ENSG00000149260), PEF1 (ENSG00000162517), CAPN2 (ENSG00000162909), CAPN13 (ENSG00000162949), CAPN12 (ENSG00000182472), CAPN8 (ENSG00000203697), CAPN14 (ENSG00000214711), PDCD6 (ENSG00000249915), CAPNS2 (ENSG00000256812)

Protein

Protein identifiers

Calpain-11 — Q9UMQ6 (reviewed: Q9UMQ6)

Alternative names: Calcium-activated neutral proteinase 11

All UniProt accessions (3): Q9UMQ6, E9PIX3, E9PQZ4

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.

Subunit / interactions. Heterodimer of a large (catalytic) and a small (regulatory) subunit.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Tissue specificity. Highest expression in testis.

Similarity. Belongs to the peptidase C2 family.

RefSeq proteins (1): NP_008989* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000169	Pept_cys_AS	Active_site
IPR001300	Peptidase_C2_calpain_cat	Domain
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
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, PF13833

Enzyme classification (BRENDA):

• EC 3.4.22.B31 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (26 total): binding site 10, sequence variant 5, region of interest 4, domain 3, active site 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMQ6-F1	87.10	0.59

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): 320; 139; 296

Ligand- & substrate-binding residues (10): 623; 625; 627; 629; 634; 653; 655; 657; 659; 664

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: 66 (showing top): GOCC_SECRETORY_GRANULE, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, MODULE_99, BOQUEST_STEM_CELL_DN, MYB_Q5_01, GOCC_SECRETORY_VESICLE, GOBP_PROTEOLYSIS, GOCC_ACROSOMAL_VESICLE, GOMF_PEPTIDASE_ACTIVITY, GOMF_CALCIUM_DEPENDENT_CYSTEINE_TYPE_ENDOPEPTIDASE_ACTIVITY, WIERENGA_STAT5A_TARGETS_DN, JNK_DN.V1_DN, DCA_UP.V1_UP, PTEN_DN.V1_UP, MIR6825_5P

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (6): calcium-dependent cysteine-type endopeptidase activity (GO:0004198), calcium ion binding (GO:0005509), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): acrosomal vesicle (GO:0001669), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

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 metabolic process	1
cysteine-type endopeptidase activity	1
metal ion binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
secretory granule	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

859 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPN11	SPATS1	Q496A3	608
CAPN11	SPATA3	Q8NHX4	523
CAPN11	CAST	P20810	519
CAPN11	SPACA4	Q8TDM5	500
CAPN11	GARIN1B	Q96KD3	479
CAPN11	UBQLN3	Q9H347	408
CAPN11	HS1BP3	Q53T59	380
CAPN11	TMEM225	Q6GV28	379
CAPN11	TOR2A	Q5JU69	358
CAPN11	TMEM63B	Q5T3F8	357
CAPN11	NUP210L	Q5VU65	356
CAPN11	GSR	P00390	346
CAPN11	REEP4	Q9H6H4	327
CAPN11	TMEM270	Q6UE05	305
CAPN11	MRPL15	Q9P015	299

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CAPN11	EIF3G	psi-mi:“MI:0915”(physical association)	0.400
XRCC6	CAPN11	psi-mi:“MI:0915”(physical association)	0.370
CAPN11	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.370
CAPN11	UNG	psi-mi:“MI:0915”(physical association)	0.370
CAPN11	ANAPC11	psi-mi:“MI:0915”(physical association)	0.370
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (16): CAPN11 (Co-fractionation), SKIV2L2 (Co-fractionation), CAPN11 (Proximity Label-MS), CAPN11 (Affinity Capture-MS), CAPN11 (Affinity Capture-MS), CAPN12 (Negative Genetic), CAPN2 (Negative Genetic), CAPN3 (Negative Genetic), CAPN8 (Negative Genetic), CAPN9 (Negative Genetic), CAPN11 (Cross-Linking-MS (XL-MS)), SSR3 (Cross-Linking-MS (XL-MS)), CAPN11 (Two-hybrid), XRCC6 (Two-hybrid), PRKAR1A (Two-hybrid)

ESM2 similar proteins: A2IBH5, A2IBY7, A3KGF7, A4D1Z8, A8MX76, E7F9T0, F6Q2R9, O88644, O89040, P02522, P02523, P02524, P07318, P07530, P13943, P19141, P26998, P43320, P49221, P50281, P53672, P53674, P53690, P55165, P62696, P62697, P62698, Q007T1, Q05714, Q10739, Q2LEC2, Q3UW68, Q4V8Q1, Q5BK10, Q5EF38, Q5RES1, Q6J756, Q6MZZ7, Q91318, Q91320

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3568 predictions. Top by Δscore:

Variant	Effect	Δscore
6:44166802:GAGGA:G	donor_gain	1.0000
6:44169276:A:G	acceptor_gain	1.0000
6:44169277:GCA:G	acceptor_gain	1.0000
6:44169527:CCAAG:C	donor_loss	1.0000
6:44169528:CAAG:C	donor_loss	1.0000
6:44169529:AAGG:A	donor_loss	1.0000
6:44169530:AGGTG:A	donor_loss	1.0000
6:44169531:GGT:G	donor_loss	1.0000
6:44169532:GT:G	donor_loss	1.0000
6:44169904:A:AG	acceptor_gain	1.0000
6:44169905:G:GG	acceptor_gain	1.0000
6:44169905:GGAT:G	acceptor_gain	1.0000
6:44169972:CTCGG:C	donor_loss	1.0000
6:44169974:CGG:C	donor_loss	1.0000
6:44169976:GT:G	donor_loss	1.0000
6:44169977:T:A	donor_loss	1.0000
6:44172935:CACA:C	acceptor_loss	1.0000
6:44172937:CA:C	acceptor_loss	1.0000
6:44172938:A:AG	acceptor_gain	1.0000
6:44172939:G:GA	acceptor_gain	1.0000
6:44172939:GA:G	acceptor_gain	1.0000
6:44172939:GATTT:G	acceptor_gain	1.0000
6:44173034:G:GG	donor_gain	1.0000
6:44173069:GCCAA:G	donor_gain	1.0000
6:44173071:CAA:C	donor_gain	1.0000
6:44173074:G:GG	donor_gain	1.0000
6:44173387:G:GG	donor_gain	1.0000
6:44176148:GGAT:G	donor_gain	1.0000
6:44176149:GATG:G	donor_gain	1.0000
6:44176336:CAGG:C	donor_loss	1.0000

AlphaMissense

4942 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:44169517:T:A	W109R	0.997
6:44169517:T:C	W109R	0.997
6:44173070:C:A	A220D	0.996
6:44176316:T:A	W327R	0.996
6:44176316:T:C	W327R	0.996
6:44176651:T:C	F358L	0.995
6:44176653:C:A	F358L	0.995
6:44176653:C:G	F358L	0.995
6:44176956:T:A	W399R	0.995
6:44176956:T:C	W399R	0.995
6:44180123:T:C	F534L	0.995
6:44180125:C:A	F534L	0.995
6:44180125:C:G	F534L	0.995
6:44176328:T:A	W331R	0.994
6:44176328:T:C	W331R	0.994
6:44180124:T:C	F534S	0.993
6:44180133:G:C	R537P	0.993
6:44169519:G:C	W109C	0.992
6:44169519:G:T	W109C	0.992
6:44172989:C:A	P193H	0.992
6:44176318:G:C	W327C	0.992
6:44176318:G:T	W327C	0.992
6:44176866:T:C	F369L	0.992
6:44176868:C:A	F369L	0.992
6:44176868:C:G	F369L	0.992
6:44176958:G:C	W399C	0.992
6:44176958:G:T	W399C	0.992
6:44177347:T:C	L448P	0.992
6:44173059:G:C	E216D	0.991
6:44173059:G:T	E216D	0.991

dbSNP variants (sampled 300 via entrez): RS1000074431 (6:44163764 C>T), RS1000107415 (6:44158266 A>G), RS1000112673 (6:44179831 G>A), RS1000122881 (6:44163911 C>T), RS1000334511 (6:44183024 C>T), RS1000345621 (6:44161222 T>G), RS1000491418 (6:44175935 A>G), RS1000506446 (6:44162549 T>C), RS1000568806 (6:44162315 C>G), RS1000719667 (6:44181160 G>A), RS1000771561 (6:44175031 C>A,T), RS1000778602 (6:44168060 A>G), RS1000789100 (6:44183374 G>A,T), RS1000961760 (6:44159061 C>A), RS1001022068 (6:44179730 TG>T,TGG)

Disease associations

OMIM: gene MIM:604822 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005956_58	Waist-to-hip ratio adjusted for BMI	7.000000e-26
GCST005957_1	Waist-to-hip ratio adjusted for BMI (age <50)	2.000000e-14
GCST005958_2	Waist-to-hip ratio adjusted for BMI (age >50)	2.000000e-19
GCST005962_2	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-31
GCST90002404_260	Red cell distribution width	7.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, decreases expression	2
Zinc	increases expression, affects cotreatment, affects expression	2
trichostatin A	increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
theaflavin-3,3’-digallate	affects expression	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	affects response to substance	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Menthol	decreases expression	1
Tetradecanoylphorbol Acetate	affects cotreatment, affects expression	1

Clinical trials (associated diseases)

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