CAPN13

Summary

CAPN13 (calpain 13, HGNC:16663) is a protein-coding gene on chromosome 2p23.1, encoding Calpain-13 (Q6MZZ7). Probable non-lysosomal thiol-protease.

The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes a member of the calpain large subunit family.

Source: NCBI Gene 92291 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 147 total
• MANE Select transcript: NM_144575

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16663
Approved symbol	CAPN13
Name	calpain 13
Location	2p23.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23523
Ensembl gene	ENSG00000162949
Ensembl biotype	protein_coding
OMIM	610228
Entrez	92291

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000295055, ENST00000450650, ENST00000458085, ENST00000465450, ENST00000465960, ENST00000485248, ENST00000490786, ENST00000946472, ENST00000946473, ENST00000946474, ENST00000946475, ENST00000946476, ENST00000946477

RefSeq mRNA: 1 — MANE Select: NM_144575 NM_144575

CCDS: CCDS46252

Canonical transcript exons

ENST00000295055 — 23 exons

Exon	Start	End
ENSE00001191511	30741908	30741964
ENSE00001191519	30753053	30753198
ENSE00001191562	30751103	30751251
ENSE00001250648	30754290	30754364
ENSE00001372943	30736503	30736571
ENSE00001382037	30738400	30738457
ENSE00001386525	30738235	30738293
ENSE00001550115	30722771	30723236
ENSE00001554488	30807302	30807446
ENSE00001662606	30743383	30743579
ENSE00003481682	30758046	30758137
ENSE00003492051	30777567	30777639
ENSE00003499290	30730730	30730786
ENSE00003503004	30745723	30745734
ENSE00003518240	30734449	30734524
ENSE00003584015	30770313	30770449
ENSE00003597570	30787128	30787357
ENSE00003613842	30731344	30731399
ENSE00003638801	30763082	30763156
ENSE00003662956	30764132	30764306
ENSE00003671966	30775930	30776045
ENSE00003685613	30742326	30742359
ENSE00003692355	30732438	30732566

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 98.15.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4669 / max 142.1371, expressed in 319 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27669	1.3207	261
27670	0.1124	54
27671	0.0337	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	98.15	gold quality
nasal cavity epithelium	UBERON:0005384	97.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.23	gold quality
rectum	UBERON:0001052	95.62	gold quality
nasal cavity mucosa	UBERON:0001826	94.19	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.18	gold quality
oocyte	CL:0000023	92.93	gold quality
ileal mucosa	UBERON:0000331	90.48	gold quality
jejunal mucosa	UBERON:0000399	90.35	gold quality
islet of Langerhans	UBERON:0000006	90.32	gold quality
mucosa of transverse colon	UBERON:0004991	90.29	gold quality
duodenum	UBERON:0002114	89.89	gold quality
secondary oocyte	CL:0000655	88.93	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.57	gold quality
small intestine	UBERON:0002108	86.86	gold quality
upper arm skin	UBERON:0004263	86.83	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.10	gold quality
cardiac muscle of right atrium	UBERON:0003379	85.06	gold quality
colonic mucosa	UBERON:0000317	85.05	gold quality
left ventricle myocardium	UBERON:0006566	84.92	gold quality
bronchial epithelial cell	CL:0002328	84.10	gold quality
body of stomach	UBERON:0001161	83.75	gold quality
bronchus	UBERON:0002185	83.47	gold quality
epithelial cell of pancreas	CL:0000083	83.28	gold quality
stomach	UBERON:0000945	83.10	gold quality
pancreas	UBERON:0001264	81.94	gold quality
jejunum	UBERON:0002115	81.84	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.70	gold quality
endothelial cell	CL:0000115	80.60	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting CAPN13, 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-4776-3P	100.00	68.73	1340
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6871-3P	99.43	68.85	741
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-323A-5P	98.59	65.13	651
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-558	97.50	67.16	977
HSA-MIR-6781-3P	97.44	66.85	970
HSA-MIR-526B-5P	97.41	67.99	1074
HSA-MIR-2682-3P	97.10	66.16	840
HSA-MIR-4662A-3P	97.02	67.77	941
HSA-MIR-6879-3P	93.93	64.00	759

Literature-anchored findings (GeneRIF, showing 1)

• Inactivating mutations of tumor suppressor genes ABCA1 and CAPN13 in colorectal cancers. (PMID:32088085)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
mus_musculus	Capn13	ENSMUSG00000043705
rattus_norvegicus	Capn13	ENSRNOG00000032375
drosophila_melanogaster	CalpB	FBGN0025866
drosophila_melanogaster	Pef	FBGN0033529
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), CAPN10 (ENSG00000142330), CAPN5 (ENSG00000149260), PEF1 (ENSG00000162517), CAPN2 (ENSG00000162909), CAPN12 (ENSG00000182472), CAPN8 (ENSG00000203697), CAPN14 (ENSG00000214711), PDCD6 (ENSG00000249915), CAPNS2 (ENSG00000256812)

Protein

Protein identifiers

Calpain-13 — Q6MZZ7 (reviewed: Q6MZZ7)

Alternative names: Calcium-activated neutral proteinase 13

All UniProt accessions (3): F5GYA7, H7C1Z4, Q6MZZ7

UniProt curated annotations — full annotation on UniProt →

Function. Probable non-lysosomal thiol-protease.

Tissue specificity. Weakly expressed in lung and testis. Weakly or not expressed in other tissues.

Similarity. Belongs to the peptidase C2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6MZZ7-1	1	yes
Q6MZZ7-2	2

RefSeq proteins (1): NP_653176* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001300	Peptidase_C2_calpain_cat	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR022682	Calpain_domain_III	Domain
IPR022684	Calpain_cysteine_protease	Family
IPR036213	Calpain_III_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR054069	CAPN3/13-like_C_EFh	Domain

Pfam: PF00648, PF01067, PF21875

UniProt features (26 total): helix 9, strand 4, domain 3, sequence variant 3, active site 3, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2I7A	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6MZZ7-F1	83.25	0.45

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): 93; 249; 273

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: 30 (showing top): SABATES_COLORECTAL_ADENOMA_SIZE_DN, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, GOMF_CALCIUM_DEPENDENT_CYSTEINE_TYPE_ENDOPEPTIDASE_ACTIVITY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_DN, DUTERTRE_ESTRADIOL_RESPONSE_24HR_DN, GSE10239_MEMORY_VS_KLRG1HIGH_EFF_CD8_TCELL_UP, chr2p23, MURARO_PANCREAS_BETA_CELL, DESCARTES_MAIN_FETAL_PARIETAL_AND_CHIEF_CELLS, DESCARTES_FETAL_EYE_CORNEAL_AND_CONJUNCTIVAL_EPITHELIAL_CELLS, DESCARTES_FETAL_KIDNEY_URETERIC_BUD_CELLS, DESCARTES_FETAL_LUNG_CILIATED_EPITHELIAL_CELLS

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

GO Molecular Function (4): calcium-dependent cysteine-type endopeptidase activity (GO:0004198), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (1): cytoplasm (GO:0005737)

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
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

957 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPN13	CALML6	Q8TD86	517
CAPN13	CALML4	Q96GE6	517
CAPN13	CALML5	Q9NZT1	517
CAPN13	CALML3	P27482	516
CAPN13	CALM1	P02593	514
CAPN13	A0A494C0M2	A0A494C0M2	434
CAPN13	ANKRD39	Q53RE8	385
CAPN13	EEIG2	Q5T8I3	357
CAPN13	BACE2	Q9Y5Z0	356
CAPN13	YPEL5	P62699	343
CAPN13	CAST	P20810	329
CAPN13	LRRIQ3	A6PVS8	322
CAPN13	ADGB	Q8N7X0	311
CAPN13	CFAP299	Q6V702	309
CAPN13	LCLAT1	Q6UWP7	307

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CAPN13	SFSWAP	psi-mi:“MI:0914”(association)	0.530
CAPN13	EIF4E2	psi-mi:“MI:0914”(association)	0.350
ATMIN	SPECC1L	psi-mi:“MI:0914”(association)	0.350
CKAP2	WDR46	psi-mi:“MI:0914”(association)	0.350
ATMIN	OAS2	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): ZC3H4 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), CAPN13 (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SAFB2 (Affinity Capture-MS), DIDO1 (Affinity Capture-MS), PRRC2A (Affinity Capture-MS), SF1 (Affinity Capture-MS), TJP2 (Affinity Capture-MS), EWSR1 (Affinity Capture-MS), SAFB (Affinity Capture-MS), EIF4E2 (Affinity Capture-MS), CAPN13 (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), ZC3H4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RQE8, F1S5L4, O43010, O77512, P06592, P13233, P14714, P42498, P49895, P55004, P97564, Q07071, Q09305, Q0P464, Q0P4Y1, Q1LYL8, Q2KHV5, Q2KIR7, Q3UW68, Q5BK10, Q5FW57, Q5GJ77, Q5PQT3, Q5RFP0, Q60462, Q61586, Q62240, Q64112, Q6IB77, Q6MZZ7, Q6P5U7, Q6QN13, Q6QR59, Q6V915, Q7L7V1, Q804E1, Q8CBA2, Q8T773, Q8WU03, Q91754

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	120
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4666 predictions. Top by Δscore:

Variant	Effect	Δscore
2:30730724:TCTTA:T	donor_loss	1.0000
2:30730725:CTTAC:C	donor_loss	1.0000
2:30730726:TTA:T	donor_loss	1.0000
2:30730728:A:AG	donor_loss	1.0000
2:30730729:CCTG:C	donor_loss	1.0000
2:30730783:TCCA:T	acceptor_gain	1.0000
2:30730784:CCAC:C	acceptor_gain	1.0000
2:30730785:CA:C	acceptor_gain	1.0000
2:30730787:C:CC	acceptor_gain	1.0000
2:30731400:C:CC	acceptor_gain	1.0000
2:30732436:A:AC	donor_gain	1.0000
2:30732437:C:CC	donor_gain	1.0000
2:30732437:CTTG:C	donor_gain	1.0000
2:30732574:C:CT	acceptor_gain	1.0000
2:30738236:T:TA	donor_gain	1.0000
2:30738237:C:A	donor_gain	1.0000
2:30741971:C:CT	acceptor_gain	1.0000
2:30761450:G:C	donor_gain	1.0000
2:30764125:GACTT:G	donor_loss	1.0000
2:30764126:ACTT:A	donor_loss	1.0000
2:30764127:CTTA:C	donor_loss	1.0000
2:30764128:TTAC:T	donor_loss	1.0000
2:30764129:TA:T	donor_loss	1.0000
2:30764130:ACC:A	donor_gain	1.0000
2:30764131:CCC:C	donor_gain	1.0000
2:30764131:CCCCA:C	donor_gain	1.0000
2:30777561:TCTTA:T	donor_loss	1.0000
2:30777562:CTTAC:C	donor_loss	1.0000
2:30777563:TTA:T	donor_loss	1.0000
2:30777564:TA:T	donor_loss	1.0000

AlphaMissense

4437 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:30754292:A:C	F313L	0.986
2:30754292:A:T	F313L	0.986
2:30754294:A:G	F313L	0.986
2:30787206:G:C	F40L	0.981
2:30787206:G:T	F40L	0.981
2:30787208:A:G	F40L	0.981
2:30775939:G:C	F126L	0.978
2:30775939:G:T	F126L	0.978
2:30775941:A:G	F126L	0.978
2:30775933:G:C	F128L	0.976
2:30775933:G:T	F128L	0.976
2:30775935:A:G	F128L	0.976
2:30753168:G:C	F324L	0.974
2:30753168:G:T	F324L	0.974
2:30753170:A:G	F324L	0.974
2:30770326:T:G	K171Q	0.974
2:30787221:A:C	F35L	0.974
2:30787221:A:T	F35L	0.974
2:30787223:A:G	F35L	0.974
2:30770324:C:A	K171N	0.973
2:30770324:C:G	K171N	0.973
2:30770327:C:A	E170D	0.971
2:30770327:C:G	E170D	0.971
2:30770345:G:C	F164L	0.971
2:30770345:G:T	F164L	0.971
2:30770347:A:G	F164L	0.971
2:30770412:T:A	D142V	0.970
2:30754352:C:A	W293C	0.968
2:30754352:C:G	W293C	0.968
2:30770448:A:G	F130S	0.966

dbSNP variants (sampled 300 via entrez): RS1000014134 (2:30784900 G>A), RS1000078129 (2:30756915 A>G), RS1000118728 (2:30760926 G>A), RS1000134391 (2:30754483 G>A,T), RS1000146042 (2:30784592 A>G), RS1000166633 (2:30798505 G>A,C,T), RS1000187610 (2:30748832 C>A), RS1000251936 (2:30746442 T>C), RS1000272160 (2:30754212 T>C), RS1000298201 (2:30795101 A>G), RS1000308597 (2:30789190 C>T), RS1000313499 (2:30740726 T>G), RS1000393927 (2:30792404 G>C), RS1000407153 (2:30761171 C>T), RS1000444272 (2:30781481 G>T)

Disease associations

OMIM: gene MIM:610228 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002560_2	Type 2 diabetes	2.000000e-07
GCST008759_35	Intake of total sugars	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010158	sugar consumption measurement

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
Nickel	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
glycidamide	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Zoledronic Acid	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	increases methylation, increases abundance	1
Estradiol	decreases expression	1
Smoke	decreases expression, increases abundance	1
Aflatoxin B1	increases methylation	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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