CRISP2

gene
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Also known as CRISP-2CT36

Summary

CRISP2 (cysteine rich secretory protein 2, HGNC:12024) is a protein-coding gene on chromosome 6p12.3, encoding Cysteine-rich secretory protein 2 (P16562). May regulate some ion channels’ activity and thereby regulate calcium fluxes during sperm capacitation.

Predicted to be involved in sexual reproduction. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 7180 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 39 total
  • MANE Select transcript: NM_003296

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:12024
Approved symbolCRISP2
Namecysteine rich secretory protein 2
Location6p12.3
Locus typegene with protein product
StatusApproved
AliasesCRISP-2, CT36
Ensembl geneENSG00000124490
Ensembl biotypeprotein_coding
OMIM187430
Entrez7180

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000339139, ENST00000616725, ENST00000618917, ENST00000856936, ENST00000856937, ENST00000856938, ENST00000856939, ENST00000856940

RefSeq mRNA: 6 — MANE Select: NM_003296 NM_001142407, NM_001142408, NM_001142417, NM_001142435, NM_001261822, NM_003296

CCDS: CCDS4928

Canonical transcript exons

ENST00000339139 — 10 exons

ExonStartEnd
ENSE000011387884969583649695924
ENSE000011387954969786049697957
ENSE000011388114969980449699891
ENSE000013680274971347549713543
ENSE000013757294969235949692900
ENSE000013782964971250149712604
ENSE000013813804971128549711321
ENSE000013836874970913149709205
ENSE000024449674969836249698507
ENSE000024723514970066849700784

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 99.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9553 / max 714.0675, expressed in 39 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
739170.733629
739180.221719

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
spermCL:000001999.99gold quality
male germ cellCL:000001599.76gold quality
adult organismUBERON:000702399.25gold quality
left testisUBERON:000453399.05gold quality
right testisUBERON:000453498.98gold quality
right uterine tubeUBERON:000130297.76gold quality
testisUBERON:000047396.26gold quality
pancreatic ductal cellCL:000207992.48gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047391.09gold quality
bronchial epithelial cellCL:000232890.74gold quality
epithelium of bronchusUBERON:000203189.81gold quality
bronchusUBERON:000218588.94gold quality
lower esophagus mucosaUBERON:003583487.99gold quality
epithelial cell of pancreasCL:000008383.98silver quality
minor salivary glandUBERON:000183079.78gold quality
caput epididymisUBERON:000435879.62gold quality
gall bladderUBERON:000211079.61gold quality
saliva-secreting glandUBERON:000104479.00gold quality
olfactory segment of nasal mucosaUBERON:000538678.75gold quality
bone marrowUBERON:000237175.99gold quality
mouth mucosaUBERON:000372975.52gold quality
cauda epididymisUBERON:000436074.57gold quality
trabecular bone tissueUBERON:000248374.53gold quality
seminal vesicleUBERON:000099873.69gold quality
fallopian tubeUBERON:000388972.85gold quality
oviduct epitheliumUBERON:000480471.70gold quality
nasal cavity mucosaUBERON:000182671.36gold quality
choroid plexus epitheliumUBERON:000391170.39gold quality
corpus epididymisUBERON:000435969.67gold quality
parotid glandUBERON:000183168.90silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

ExperimentMarker?Max mean expression
E-GEOD-134144yes12207.97
E-HCAD-38yes5996.75
E-ANND-3no3.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting CRISP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-6870-5P99.9968.552115
HSA-LET-7F-2-3P99.9870.982588
HSA-MIR-1185-1-3P99.9871.042593
HSA-MIR-1185-2-3P99.9871.042593
HSA-MIR-27A-3P99.9872.132955
HSA-MIR-27B-3P99.9872.132955
HSA-MIR-998599.9872.112939
HSA-MIR-4723-5P99.9768.702034
HSA-MIR-569899.9768.492029
HSA-MIR-7111-5P99.9768.482062
HSA-MIR-548AJ-3P99.9673.385345
HSA-MIR-548X-3P99.9673.385345
HSA-MIR-767-5P99.9570.85993
HSA-MIR-548J-3P99.9472.614881
HSA-MIR-6835-3P99.9370.492904
HSA-MIR-4778-3P99.9370.401818
HSA-MIR-548AE-3P99.9372.664867
HSA-MIR-548AH-3P99.9372.544872
HSA-MIR-548AM-3P99.9372.544872
HSA-MIR-548AQ-3P99.9372.664867
HSA-MIR-806299.8868.43995
HSA-MIR-582-5P99.4770.792635
HSA-MIR-501-3P99.3366.12651
HSA-MIR-502-3P99.3366.12651
HSA-MIR-491-3P98.8868.861224
HSA-MIR-487A-5P98.8569.37993
HSA-MIR-487B-5P98.8569.48987
HSA-MIR-7155-5P98.6566.141290
HSA-MIR-4700-5P98.6367.431915
HSA-MIR-431798.4967.09987

Literature-anchored findings (GeneRIF, showing 15)

  • TPX1 is a component of the sperm acrosome that remains associated with sperm after capacitation and acrosome reaction , and is relevant for sperm-oocyte interaction. (PMID:15734896)
  • The protein level and localization of TPX1 were altered in patients with spermatogenic arrest and in infertile men with oligoasthenoteratospermia syndrome. (PMID:16759931)
  • Polymorphisms within the CRISP2 gene have no significant association with male infertility. (PMID:18550510)
  • Additional transcription changes likely associated with Th2-like eosinophilic inflammation were prominent and included decreased CRISP2&3. (PMID:20625511)
  • The down-regulation of CRISP2 mRNA and protein expressions in the sperm of asthenospermia patients may be closely related with decreased sperm motility. (PMID:21485539)
  • CRISP2 rescues the phenotype of yeast mutants lacking Pry function and purified CRISP2 binds cholesterol in vitro, indicating that lipid binding is a conserved function of the CAP superfamily proteins. (PMID:23027975)
  • Study shows the re-association of sperm acrosomal CRISP2 at the EqS during the acrosome reaction. Data showed that F-actin is not involved in the relocalization of CRISP2. Found that basic,but not acidic, conditions can solubilize CRISP2 from sperm cells. (PMID:23661501)
  • Preliminary insight into the mechanism leading to the reduced CRISP2 expression in asthenozoospermia, offering a potential therapeutic target for treating male infertility or for male contraception. (PMID:25505194)
  • Crisp2 genetic defects in sperm from humans and mice result in male infertility. (PMID:26786179)
  • Results identified CRISP2 as a potential binding protein of PSP94 from human sperm. (PMID:27161017)
  • low expression of CRISP2 protein rather than its mRNA was observed in the ejaculated spermatozoa from asthenoteratozoospermic patients as compared with normozoospermic males (PMID:27517483)
  • The integrated network analysis identified BRCA1 and CRISP2 differentially methylated regions (DMR) as the most central disease-associated DNA methylation biomarkers. Moreover, methylation changes at BRCA1 and CRISP2 specific CpG sites were consistently associated with subclinical atherosclerosis measures. (PMID:28698603)
  • DNA methylation profiling identifies epigenetic differences between early versus late stages of diabetic chronic kidney disease. (PMID:33146725)
  • Discovery and validation of novel biomarkers for detection of cervical cancer. (PMID:33624385)
  • CRISP2, CATSPER1 and PATE1 Expression in Human Asthenozoospermic Semen. (PMID:34440724)

Cross-species orthologs

46 orthologs

OrganismSymbolGene ID
mus_musculusCrisp2ENSMUSG00000023930
rattus_norvegicusCrisp2ENSRNOG00000013225
drosophila_melanogasterAg5rFBGN0015010
drosophila_melanogasterAg5r2FBGN0020508
drosophila_melanogasterCG9400FBGN0030562
drosophila_melanogasterCG10651FBGN0032853
drosophila_melanogasterCG9822FBGN0034623
drosophila_melanogasterCG17974FBGN0034624
drosophila_melanogasterCG3640FBGN0035042
drosophila_melanogasterCG8072FBGN0036070
drosophila_melanogasterCG6628FBGN0036072
drosophila_melanogasterscpr-CFBGN0037879
drosophila_melanogasterscpr-BFBGN0037888
drosophila_melanogasterscpr-AFBGN0037889
drosophila_melanogasterCG8483FBGN0038126
drosophila_melanogasterCG30486FBGN0050486
drosophila_melanogasterantrFBGN0050488
drosophila_melanogasterCG31286FBGN0051286
drosophila_melanogasterCG32313FBGN0052313
drosophila_melanogasterCG32679FBGN0052679
drosophila_melanogasterCG34002FBGN0054002
drosophila_melanogasterCG17575FBGN0250842
drosophila_melanogasterCG42564FBGN0260766
drosophila_melanogasterCG42780FBGN0261848
drosophila_melanogasterCG43775FBGN0264297
drosophila_melanogasterCG43776FBGN0264298
drosophila_melanogasterCG43777FBGN0264299
caenorhabditis_elegansWBGENE00004742
caenorhabditis_elegansWBGENE00007397
caenorhabditis_elegansWBGENE00008027
caenorhabditis_elegansWBGENE00008028
caenorhabditis_elegansWBGENE00008029
caenorhabditis_elegansWBGENE00008030
caenorhabditis_elegansWBGENE00008625
caenorhabditis_elegansWBGENE00009891
caenorhabditis_elegansWBGENE00009895
caenorhabditis_elegansWBGENE00009896
caenorhabditis_elegansWBGENE00012816
caenorhabditis_elegansWBGENE00013971
caenorhabditis_elegansWBGENE00013972
caenorhabditis_elegansWBGENE00015246
caenorhabditis_elegansWBGENE00017055
caenorhabditis_elegansWBGENE00017183
caenorhabditis_elegansWBGENE00019178
caenorhabditis_elegansWBGENE00019179
caenorhabditis_elegansWBGENE00021780

Paralogs (13): CRISP3 (ENSG00000096006), R3HDML (ENSG00000101074), CRISPLD2 (ENSG00000103196), CRISPLD1 (ENSG00000121005), GLIPR2 (ENSG00000122694), CRISP1 (ENSG00000124812), PI15 (ENSG00000137558), GLIPR1 (ENSG00000139278), CLEC18B (ENSG00000140839), CLEC18A (ENSG00000157322), CLEC18C (ENSG00000157335), GLIPR1L1 (ENSG00000173401), GLIPR1L2 (ENSG00000180481)

Protein

Protein identifiers

Cysteine-rich secretory protein 2P16562 (reviewed: P16562)

Alternative names: Cancer/testis antigen 36, Testis-specific protein TPX-1

All UniProt accessions (2): A0A024RD74, P16562

UniProt curated annotations — full annotation on UniProt →

Function. May regulate some ion channels’ activity and thereby regulate calcium fluxes during sperm capacitation.

Subunit / interactions. Interacts with NSUN4 isoform 3.

Subcellular location. Secreted.

Tissue specificity. Testis and epididymis.

Similarity. Belongs to the CRISP family.

Isoforms (2)

UniProt IDNamesCanonical?
P16562-11yes
P16562-22

RefSeq proteins (6): NP_001135879, NP_001135880, NP_001135889, NP_001135907, NP_001248751, NP_003287* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001283CRISP-relatedFamily
IPR003582ShKT_domDomain
IPR013871Cysteine_rich_secretoryDomain
IPR014044CAP_domDomain
IPR018244Allrgn_V5/Tpx1_CSConserved_site
IPR034117SCP_CRISPDomain
IPR035940CAP_sfHomologous_superfamily
IPR042076Crisp-like_domHomologous_superfamily

Pfam: PF00188, PF08562

UniProt features (18 total): disulfide bond 5, sequence conflict 2, strand 2, helix 2, domain 2, signal peptide 1, chain 1, sequence variant 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
2CQ7SOLUTION NMR

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P16562-F193.330.88

Functional residue map

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

Disulfide bonds (5): 189–196, 192–201, 205–238, 214–232, 223–236

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 76 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, chr6p12, GNF2_CCNA1, MORF_EPHA7, MORF_RAB3A, MORF_BMPR2, MORF_DCC, WEBER_METHYLATED_HCP_IN_FIBROBLAST_DN, LEE_LIVER_CANCER_MYC_TGFA_DN, WEBER_METHYLATED_HCP_IN_SPERM_DN, YOSHIMURA_MAPK8_TARGETS_UP, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, BRUINS_UVC_RESPONSE_MIDDLE

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure1

Protein interactions and networks

STRING

1296 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CRISP2PGK2P07205813
CRISP2CATSPER1Q8NEC5751
CRISP2PLB1Q6P1J6655
CRISP2IL4I1Q96RQ9653
CRISP2LTA4HP09960589
CRISP2GGNBP2Q9H3C7579
CRISP2IZUMO1Q8IYV9563
CRISP2PATE1Q8WXA2562
CRISP2AKAP4Q5JQC9542
CRISP2PRM2P04554528
CRISP2TMEM37Q8WXS4527
CRISP2PLA2G2AP14555515
CRISP2IZUMO3Q5VZ72493
CRISP2PLCZ1Q86YW0492
CRISP2PKDREJQ9NTG1491

IntAct

5 interactions, top by confidence:

ABTypeScore
CRISP2TUBA4Apsi-mi:“MI:0914”(association)0.530
CREB3CRISP2psi-mi:“MI:0915”(physical association)0.370
CRISP2HSPA5psi-mi:“MI:0914”(association)0.350
CRISP2LRP5psi-mi:“MI:0914”(association)0.350

BioGRID (51): TACC3 (Affinity Capture-MS), CTSF (Affinity Capture-MS), CNTNAP3 (Affinity Capture-MS), NLGN2 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), CRISP2 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), NLGN2 (Affinity Capture-MS), TACC3 (Affinity Capture-MS), CNTNAP3 (Affinity Capture-MS), PLXNA1 (Affinity Capture-MS), PCSK6 (Affinity Capture-MS), CELSR1 (Affinity Capture-MS), SEMA3B (Affinity Capture-MS)

ESM2 similar proteins: A0A0D3QS98, A0A0D3QS99, A2A5I3, O19010, O19011, O42596, P01137, P04202, P04629, P07200, P09533, P16562, P17246, P18341, P35739, P50414, P54108, P54831, P57110, Q01974, Q38HS2, Q3KPV7, Q3UFB7, Q505J3, Q5R7Y0, Q5T4F7, Q60477, Q658N2, Q6UWX4, Q7T141, Q7TSQ1, Q80XH4, Q8BG58, Q91009, Q99JR5, Q9CXM0, Q9D2G9, Q9EQT5, Q9GZM7, Q9H3Y0

Diamond homologs: A0A182GL09, A0A1S4EWW7, A0A218QX58, A1BQQ5, A6MFK9, A6QLZ7, A8S6B6, A9QQ26, A9YME1, B2MVK7, B9URJ1, C0ITL3, D4B327, D4P2Y4, F8J2D4, G3CJR9, O19010, O43692, P0CB15, P0DMB9, P0DMT4, P0DPU0, P0DPU1, P0DPU2, P0DPU5, P0DPV2, P0DSI3, P10736, P10737, P12020, P16562, P16563, P35759, P35760, P35778, P35779, P35780, P35781, P35782, P35783

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance34
Likely benign4
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1071 predictions. Top by Δscore:

VariantEffectΔscore
6:49695922:CCA:Cacceptor_gain1.0000
6:49695923:CAC:Cacceptor_gain1.0000
6:49695925:C:CCacceptor_gain1.0000
6:49698356:TCTTA:Tdonor_loss1.0000
6:49698357:CTTAC:Cdonor_loss1.0000
6:49698358:TTACC:Tdonor_loss1.0000
6:49698359:TACC:Tdonor_loss1.0000
6:49698360:A:ATdonor_loss1.0000
6:49698506:ACCT:Aacceptor_loss1.0000
6:49698508:CTA:Cacceptor_loss1.0000
6:49698509:T:Cacceptor_loss1.0000
6:49699799:CATA:Cdonor_gain1.0000
6:49699802:A:ACdonor_gain1.0000
6:49699803:C:CCdonor_gain1.0000
6:49700004:C:CTdonor_gain1.0000
6:49700005:T:TTdonor_gain1.0000
6:49700652:CAGCA:Cdonor_gain1.0000
6:49700667:CCAT:Cdonor_gain1.0000
6:49700783:TC:Tacceptor_gain1.0000
6:49700784:CC:Cacceptor_gain1.0000
6:49700784:CCTAA:Cacceptor_loss1.0000
6:49700785:C:CCacceptor_gain1.0000
6:49700785:CTA:Cacceptor_loss1.0000
6:49700786:T:Aacceptor_loss1.0000
6:49712499:A:ACdonor_gain1.0000
6:49712500:C:CAdonor_gain1.0000
6:49712500:CT:Cdonor_gain1.0000
6:49712500:CTA:Cdonor_gain1.0000
6:49712500:CTAA:Cdonor_gain1.0000
6:49712500:CTAAT:Cdonor_gain1.0000

AlphaMissense

1600 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
6:49692810:C:GC232S0.996
6:49692811:A:TC232S0.996
6:49699886:C:AW63C0.996
6:49699886:C:GW63C0.996
6:49700707:C:AR48S0.996
6:49700707:C:GR48S0.996
6:49700708:C:GR48T0.996
6:49697926:C:GC150S0.995
6:49697927:A:TC150S0.995
6:49698416:A:CF121L0.995
6:49698416:A:TF121L0.995
6:49698418:A:GF121L0.995
6:49698458:C:AW107C0.995
6:49698458:C:GW107C0.995
6:49699842:C:GC78S0.995
6:49699843:A:TC78S0.995
6:49700708:C:AR48M0.995
6:49692864:C:GC214S0.994
6:49692865:A:TC214S0.994
6:49695838:C:GC201S0.994
6:49695839:A:TC201S0.994
6:49697875:C:TC167Y0.994
6:49697876:A:GC167R0.994
6:49697926:C:TC150Y0.994
6:49698460:A:GW107R0.994
6:49698460:A:TW107R0.994
6:49698488:A:CN97K0.994
6:49698488:A:TN97K0.994
6:49697874:G:CC167W0.993
6:49697875:C:GC167S0.993

dbSNP variants (sampled 300 via entrez): RS1000005963 (6:49690796 T>C), RS1000032616 (6:49695432 C>T), RS1000067331 (6:49690130 A>G), RS1000128221 (6:49696358 A>G), RS1000220330 (6:49715263 T>C), RS1000251738 (6:49696501 G>T), RS1000384550 (6:49709384 C>T), RS1000389362 (6:49679272 C>A), RS1000420013 (6:49690317 C>A,T), RS1000435915 (6:49713293 G>A), RS1000682289 (6:49700974 T>C), RS1000709541 (6:49714882 C>A,G,T), RS1000726978 (6:49708036 A>G), RS1000860059 (6:49684613 T>G), RS1000879091 (6:49714805 T>C)

Disease associations

OMIM: gene MIM:187430 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): megacolon (MONDO:0001273)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

StudyTraitp-value
GCST003102_6Bone mineral density (hip) and age at menarche9.000000e-06
GCST006585_1873Blood protein levels5.000000e-107

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0004703age at menarche
EFO:0007702hip bone mineral density

MeSH disease descriptors (1)

DescriptorNameTree numbers
D008531MegacolonC06.405.469.158.701

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

ChemicalActions (top 5)PubMed papers
arseniteincreases methylation1
pentanalincreases expression1
PKF115-584affects expression1
Decitabineincreases expression1
Arsenicaffects methylation1
Atrazineincreases expression1
Benzo(a)pyreneaffects methylation1
Cadmiumdecreases expression, increases abundance1
Doxorubicindecreases expression1
Tobacco Smoke Pollutiondecreases expression1
Valproic Aciddecreases methylation1
Aflatoxin B1decreases methylation1
Lithium Chloridedecreases expression1
Cadmium Chloridedecreases expression, increases abundance1

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT04340856Not specifiedCOMPLETEDRetrospective, Uncontrolled Cohort Study on the Therapy of Chronic Megalon
NCT07470892Not specifiedNOT_YET_RECRUITINGPreoperative Fish Oil PN and Prognosis After Constipation Surgery
  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): megacolon