CRISP1

Summary

CRISP1 (cysteine rich secretory protein 1, HGNC:304) is a protein-coding gene on chromosome 6p12.3, encoding Cysteine-rich secretory protein 1 (P54107). May have a role in sperm-egg fusion and maturation.

Fertilization consists of a sequence of specific cell-cell interactions culminating in the fusion of the sperm and egg plasma membranes. Recognition, binding, and fusion occur through the interaction of complementary molecules that are localized to specific domains of the sperm and egg plasma membranes. In the sperm, the postacrosomal region or equatorial segment is involved in sperm-egg plasma membrane fusion. The protein encoded by this gene is a member of the cysteine-rich secretory protein (CRISP) family. It is expressed in the epididymis, is secreted into the epididymal lumen, and binds to the postacrosomal region of the sperm head, where it plays a role in sperm-egg fusion. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 167 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_001131

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:304
Approved symbol	CRISP1
Name	cysteine rich secretory protein 1
Location	6p12.3
Locus type	gene with protein product
Status	Approved
Aliases	CRISP-1, ARP, HUMARP, HSCRISP1D, HSCRISP1G
Ensembl gene	ENSG00000124812
Ensembl biotype	protein_coding
OMIM	601193
Entrez	167

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000329411, ENST00000335847, ENST00000505118, ENST00000507853

RefSeq mRNA: 3 — MANE Select: NM_001131 NM_001131, NM_001205220, NM_170609

CCDS: CCDS4931, CCDS4932

Canonical transcript exons

ENST00000335847 — 8 exons

Exon	Start	End
ENSE00000850446	49838437	49838525
ENSE00000850447	49840898	49840995
ENSE00000850448	49846520	49846668
ENSE00000850449	49848209	49848299
ENSE00000850450	49852001	49852129
ENSE00001329211	49857335	49857402
ENSE00002047747	49866429	49866535
ENSE00003687056	49834257	49835443

Expression profiles

Bgee: expression breadth broad, 29 present calls, max score 99.87.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9258 / max 1276.1692, expressed in 10 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73934	0.6371	9
73936	0.1819	3
73935	0.0738	4
73937	0.0330	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.87	gold quality
cauda epididymis	UBERON:0004360	99.41	gold quality
sperm	CL:0000019	96.04	gold quality
male germ cell	CL:0000015	95.39	gold quality
seminal vesicle	UBERON:0000998	94.90	gold quality
type B pancreatic cell	CL:0000169	79.58	gold quality
olfactory bulb	UBERON:0002264	79.48	gold quality
diaphragm	UBERON:0001103	71.26	gold quality
caput epididymis	UBERON:0004358	66.74	gold quality
cardiac muscle of right atrium	UBERON:0003379	63.81	gold quality
left ventricle myocardium	UBERON:0006566	63.35	gold quality
hair follicle	UBERON:0002073	62.86	gold quality
mucosa of urinary bladder	UBERON:0001259	62.71	gold quality
testis	UBERON:0000473	59.10	gold quality
quadriceps femoris	UBERON:0001377	58.89	gold quality
vastus lateralis	UBERON:0001379	58.85	gold quality
nephron tubule	UBERON:0001231	58.84	gold quality
left testis	UBERON:0004533	58.70	gold quality
right testis	UBERON:0004534	58.00	gold quality
kidney epithelium	UBERON:0004819	57.59	gold quality
adult organism	UBERON:0007023	57.54	gold quality
thymus	UBERON:0002370	57.53	gold quality
myocardium	UBERON:0002349	57.50	gold quality
metanephric glomerulus	UBERON:0004736	57.28	gold quality
nasal cavity epithelium	UBERON:0005384	56.15	gold quality
pancreatic ductal cell	CL:0002079	55.93	silver quality
epithelial cell of pancreas	CL:0000083	54.87	gold quality
buccal mucosa cell	CL:0002336	54.36	silver quality
epithelium of nasopharynx	UBERON:0001951	53.99	gold quality
tibialis anterior	UBERON:0001385	50.93	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	1316.29
E-ANND-3	yes	3.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

67 targeting CRISP1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4719	99.73	72.10	3329

Literature-anchored findings (GeneRIF, showing 4)

• CRISP1 was in the seminal plasma of normal and vasovasostomized men, but not in that of vasectomized men. The soluble concentration of CRISP1 was significantly higher in the seminal plasma of vasovasostomized men as compared with that from normal men. (PMID:20378925)
• Seminal CRISP1 combined with neutral alpha glucosidase activity can potentially distinguish between obstructive and nonobstructive azoospermia. (PMID:23987519)
• Epididymal CRISP1 mediates sperm-zona pellucida binding through its interaction with ZP3. (PMID:24334245)
• The less conserved metal-binding site in human CRISP1 remains sensitive to zinc ions to permit protein oligomerization. (PMID:33750840)

Cross-species orthologs

49 orthologs

Organism	Symbol	Gene ID
danio_rerio	glipr1b	ENSDARG00000030078
danio_rerio	glipr1a	ENSDARG00000045224
danio_rerio		ENSDARG00000103034
mus_musculus	Crisp4	ENSMUSG00000025774
rattus_norvegicus	Crisp1	ENSRNOG00000013612
drosophila_melanogaster	Ag5r	FBGN0015010
drosophila_melanogaster	Ag5r2	FBGN0020508
drosophila_melanogaster	CG9400	FBGN0030562
drosophila_melanogaster	CG10651	FBGN0032853
drosophila_melanogaster	CG9822	FBGN0034623
drosophila_melanogaster	CG17974	FBGN0034624
drosophila_melanogaster	CG3640	FBGN0035042
drosophila_melanogaster	CG8072	FBGN0036070
drosophila_melanogaster	CG6628	FBGN0036072
drosophila_melanogaster	scpr-C	FBGN0037879
drosophila_melanogaster	scpr-B	FBGN0037888
drosophila_melanogaster	scpr-A	FBGN0037889
drosophila_melanogaster	CG8483	FBGN0038126
drosophila_melanogaster	CG30486	FBGN0050486
drosophila_melanogaster	antr	FBGN0050488
drosophila_melanogaster	CG31286	FBGN0051286
drosophila_melanogaster	CG32313	FBGN0052313
drosophila_melanogaster	CG32679	FBGN0052679
drosophila_melanogaster	CG34002	FBGN0054002
drosophila_melanogaster	CG17575	FBGN0250842
drosophila_melanogaster	CG42564	FBGN0260766
drosophila_melanogaster	CG42780	FBGN0261848
drosophila_melanogaster	CG43775	FBGN0264297
drosophila_melanogaster	CG43776	FBGN0264298
drosophila_melanogaster	CG43777	FBGN0264299
caenorhabditis_elegans		WBGENE00004742
caenorhabditis_elegans		WBGENE00007397
caenorhabditis_elegans		WBGENE00008027
caenorhabditis_elegans		WBGENE00008028
caenorhabditis_elegans		WBGENE00008029
caenorhabditis_elegans		WBGENE00008030
caenorhabditis_elegans		WBGENE00008625
caenorhabditis_elegans		WBGENE00009891
caenorhabditis_elegans		WBGENE00009895
caenorhabditis_elegans		WBGENE00009896
caenorhabditis_elegans		WBGENE00012816
caenorhabditis_elegans		WBGENE00013971
caenorhabditis_elegans		WBGENE00013972
caenorhabditis_elegans		WBGENE00015246
caenorhabditis_elegans		WBGENE00017055
caenorhabditis_elegans		WBGENE00017183
caenorhabditis_elegans		WBGENE00019178
caenorhabditis_elegans		WBGENE00019179
caenorhabditis_elegans		WBGENE00021780

Paralogs (13): CRISP3 (ENSG00000096006), R3HDML (ENSG00000101074), CRISPLD2 (ENSG00000103196), CRISPLD1 (ENSG00000121005), GLIPR2 (ENSG00000122694), CRISP2 (ENSG00000124490), PI15 (ENSG00000137558), GLIPR1 (ENSG00000139278), CLEC18B (ENSG00000140839), CLEC18A (ENSG00000157322), CLEC18C (ENSG00000157335), GLIPR1L1 (ENSG00000173401), GLIPR1L2 (ENSG00000180481)

Protein

Protein identifiers

Cysteine-rich secretory protein 1 — P54107 (reviewed: P54107)

Alternative names: AEG-like protein, ARP, Acidic epididymal glycoprotein homolog

All UniProt accessions (2): A0A0K0K1I1, P54107

UniProt curated annotations — full annotation on UniProt →

Function. May have a role in sperm-egg fusion and maturation.

Tissue specificity. Caput, corpus, and cauda regions of the epididymis, the ductus deferens, sperm and seminal plasma.

Similarity. Belongs to the CRISP family.

Isoforms (2)

UniProt ID	Names	Canonical?
P54107-1	Long	yes
P54107-2	Short, CRISP-1 delta

RefSeq proteins (3): NP_001122, NP_001192149, NP_733758 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001283	CRISP-related	Family
IPR002413	V5_allergen-like	Family
IPR003582	ShKT_dom	Domain
IPR013871	Cysteine_rich_secretory	Domain
IPR014044	CAP_dom	Domain
IPR018244	Allrgn_V5/Tpx1_CS	Conserved_site
IPR034117	SCP_CRISP	Domain
IPR035940	CAP_sf	Homologous_superfamily
IPR042076	Crisp-like_dom	Homologous_superfamily

Pfam: PF00188, PF08562

UniProt features (14 total): disulfide bond 5, splice variant 2, sequence conflict 2, domain 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54107-F1	93.21	0.83

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): 195–202, 198–207, 211–244, 220–238, 229–242

Glycosylation sites (1): 230

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_SINGLE_FERTILIZATION, NKX25_02, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, MORF_ZNF10, chr6p12, TGANTCA_AP1_C, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, MORF_EPHA7, MORF_BMPR2, GOBP_PLASMA_MEMBRANE_FUSION, GOBP_MEMBRANE_ORGANIZATION

GO Biological Process (3): binding of sperm to zona pellucida (GO:0007339), fusion of sperm to egg plasma membrane involved in single fertilization (GO:0007342), regulation of acrosome reaction (GO:0060046)

GO Molecular Function (1): calcium channel regulator activity (GO:0005246)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sperm-egg recognition	1
single fertilization	1
cellular process involved in reproduction in multicellular organism	1
acrosome reaction	1
regulation of reproductive process	1
calcium channel activity	1
ion channel regulator activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1170 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRISP1	IL4I1	Q96RQ9	677
CRISP1	PLB1	Q6P1J6	674
CRISP1	LTA4H	P09960	599
CRISP1	DEFB126	Q9BYW3	575
CRISP1	PLA2G2A	P14555	570
CRISP1	IZUMO1	Q8IYV9	567
CRISP1	PIGA	P37287	559
CRISP1	TMEM37	Q8WXS4	527
CRISP1	GLIPR2	Q9H4G4	527
CRISP1	PATE1	Q8WXA2	522
CRISP1	ZAN	Q9Y493	514
CRISP1	MTDH	Q86UE4	508
CRISP1	ADAM2	P78326	492
CRISP1	AKAP4	Q5JQC9	492
CRISP1	QPCT	Q16769	478

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CRISP1	ABCA2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): ABCA2 (Affinity Capture-MS)

ESM2 similar proteins: A1BQQ5, A6MFK9, A7X4T8, B0VXV6, B7FDI0, B7FDI1, D8VNS1, F7C0L1, F8J2D4, F8S0Y4, P0CB15, P0DMT4, P12020, P54107, P60623, P79845, P84805, P84808, Q03401, Q09GJ9, Q2XXP1, Q2XXP2, Q2XXP4, Q2XXP5, Q2XXQ0, Q2XXQ1, Q2XXQ2, Q2XXQ3, Q2XXQ4, Q2XXQ5, Q2XXQ6, Q2XXQ7, Q2XXR0, Q3SB05, Q3SB06, Q3SB07, Q7T1K6, Q7YT83, Q7ZT98, Q7ZT99

Diamond homologs: A1BQQ5, A2A5I3, A5D8T8, A6QLZ7, A7X3Z4, A7X3Z7, B2MVK7, B3A0P7, F7C0L1, O19010, O43692, P04284, P0DMB9, P0DMT4, P35793, P48060, P54107, P54108, P86686, Q04108, Q28670, Q2XXP1, Q2XXP5, Q2XXQ1, Q32LB5, Q3KPV7, Q40374, Q41495, Q4V9Y5, Q58D34, Q59ZX3, Q60477, Q6UWM5, Q6UXB8, Q6UXF7, Q7T141, Q7TSQ1, Q7Z156, Q8BS03, Q8BZQ2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

826 predictions. Top by Δscore:

Variant	Effect	Δscore
6:49838435:A:AC	donor_gain	1.0000
6:49838436:C:CA	donor_gain	1.0000
6:49838436:CT:C	donor_gain	1.0000
6:49838436:CTG:C	donor_gain	1.0000
6:49838436:CTGCA:C	donor_gain	1.0000
6:49838523:CCC:C	acceptor_gain	1.0000
6:49838524:CCC:C	acceptor_gain	1.0000
6:49838526:C:CC	acceptor_gain	1.0000
6:49838527:T:C	acceptor_gain	1.0000
6:49840896:A:AC	donor_gain	1.0000
6:49840897:C:CC	donor_gain	1.0000
6:49840897:CT:C	donor_gain	1.0000
6:49846515:GTTAC:G	donor_loss	1.0000
6:49846516:TTA:T	donor_loss	1.0000
6:49846517:TAC:T	donor_loss	1.0000
6:49846518:A:AG	donor_loss	1.0000
6:49846519:C:A	donor_loss	1.0000
6:49846666:TATCT:T	acceptor_loss	1.0000
6:49846668:TCTGA:T	acceptor_loss	1.0000
6:49846669:C:CA	acceptor_loss	1.0000
6:49846670:T:A	acceptor_loss	1.0000
6:49848203:A:AC	donor_gain	1.0000
6:49848204:C:CC	donor_gain	1.0000
6:49848204:CTTA:C	donor_gain	1.0000
6:49848205:TTA:T	donor_loss	1.0000
6:49848206:TACTT:T	donor_loss	1.0000
6:49848207:A:AC	donor_gain	1.0000
6:49848207:ACT:A	donor_loss	1.0000
6:49848208:C:CC	donor_gain	1.0000
6:49848295:CAACT:C	acceptor_gain	1.0000

AlphaMissense

1658 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:49846619:C:A	W112C	0.997
6:49846619:C:G	W112C	0.997
6:49848294:C:A	W67C	0.997
6:49848294:C:G	W67C	0.997
6:49852040:C:A	R52S	0.997
6:49852040:C:G	R52S	0.997
6:49852041:C:G	R52T	0.997
6:49852041:C:A	R52M	0.996
6:49838439:C:G	C207S	0.994
6:49838440:A:T	C207S	0.994
6:49840979:G:A	S151F	0.994
6:49840964:C:G	C156S	0.993
6:49840965:A:T	C156S	0.993
6:49846598:C:A	W119C	0.993
6:49846598:C:G	W119C	0.993
6:49846621:A:G	W112R	0.993
6:49846621:A:T	W112R	0.993
6:49846577:G:C	F126L	0.992
6:49846577:G:T	F126L	0.992
6:49846579:A:G	F126L	0.992
6:49840913:C:G	C173S	0.991
6:49840914:A:T	C173S	0.991
6:49846659:C:G	C99S	0.991
6:49846660:A:T	C99S	0.991
6:49840912:A:C	C173W	0.990
6:49840913:C:T	C173Y	0.990
6:49848250:C:G	C82S	0.990
6:49848251:A:T	C82S	0.990
6:49835353:C:G	C238S	0.989
6:49835354:A:T	C238S	0.989

dbSNP variants (sampled 300 via entrez): RS1000133029 (6:49857212 A>G), RS1000150895 (6:49844410 CT>C), RS1000164697 (6:49873833 T>G), RS1000217778 (6:49836267 C>T), RS1000255240 (6:49878731 G>A,C,T), RS1000284965 (6:49878890 T>C,G), RS1000291901 (6:49870724 G>A), RS1000316088 (6:49868554 A>G), RS1000365793 (6:49876202 A>C,G), RS1000428628 (6:49870933 C>A,G,T), RS1000525531 (6:49834764 C>T), RS1000535351 (6:49835100 A>C), RS1000537171 (6:49845952 G>C,T), RS1000552913 (6:49872990 G>A), RS1000592777 (6:49877663 A>G)

Disease associations

OMIM: gene MIM:601193 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
alpha phellandrene	decreases expression	1
quercitrin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
PKF115-584	affects expression	1
Benzo(a)pyrene	affects methylation	1
Asbestos, Serpentine	increases methylation	1

Clinical trials (associated diseases)

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