CRISPLD1

Summary

CRISPLD1 (cysteine rich secretory protein LCCL domain containing 1, HGNC:18206) is a protein-coding gene on chromosome 8q21.13, encoding Cysteine-rich secretory protein LCCL domain-containing 1 (Q9H336).

Involved in face morphogenesis. Located in extracellular exosome.

Source: NCBI Gene 83690 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 92 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_031461

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18206
Approved symbol	CRISPLD1
Name	cysteine rich secretory protein LCCL domain containing 1
Location	8q21.13
Locus type	gene with protein product
Status	Approved
Aliases	Cocoacrisp, DKFZp762F133
Ensembl gene	ENSG00000121005
Ensembl biotype	protein_coding
OMIM	621340
Entrez	83690

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000262207, ENST00000517786, ENST00000519798, ENST00000520277, ENST00000523524, ENST00000915998, ENST00000915999, ENST00000916000, ENST00000959492, ENST00000959493

RefSeq mRNA: 3 — MANE Select: NM_031461 NM_001286777, NM_001286778, NM_031461

CCDS: CCDS6219, CCDS69497, CCDS75754

Canonical transcript exons

ENST00000262207 — 15 exons

Exon	Start	End
ENSE00000819708	75014812	75014912
ENSE00000819710	75016565	75016705
ENSE00000819712	75016881	75016941
ENSE00000819714	75017047	75017113
ENSE00000819716	75017320	75017450
ENSE00000819718	75019870	75019913
ENSE00000819720	75020007	75020079
ENSE00000928530	75025546	75025621
ENSE00000928531	75029387	75029517
ENSE00001173683	74985926	74986245
ENSE00001278811	75032191	75034558
ENSE00002114268	74984505	74984920
ENSE00003526195	75013987	75014102
ENSE00003545302	75012890	75013022
ENSE00003654210	75012433	75012551

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 99.19.

FANTOM5 (CAGE): breadth broad, TPM avg 8.1123 / max 209.6585, expressed in 857 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89415	6.0812	764
89417	0.9779	474
89418	0.6318	318
89416	0.2744	171
89420	0.1025	49
89421	0.0241	12
89419	0.0203	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.19	gold quality
secondary oocyte	CL:0000655	95.85	gold quality
descending thoracic aorta	UBERON:0002345	94.84	gold quality
synovial joint	UBERON:0002217	94.80	gold quality
thoracic aorta	UBERON:0001515	93.68	gold quality
ascending aorta	UBERON:0001496	93.53	gold quality
layer of synovial tissue	UBERON:0007616	92.21	gold quality
tendon of biceps brachii	UBERON:0008188	91.59	gold quality
right coronary artery	UBERON:0001625	90.21	gold quality
calcaneal tendon	UBERON:0003701	89.90	gold quality
oocyte	CL:0000023	89.51	gold quality
cartilage tissue	UBERON:0002418	89.07	gold quality
aorta	UBERON:0000947	88.56	gold quality
epithelium of mammary gland	UBERON:0003244	88.36	gold quality
mammary duct	UBERON:0001765	88.35	gold quality
ventricular zone	UBERON:0003053	87.84	gold quality
tendon	UBERON:0000043	87.56	gold quality
parietal pleura	UBERON:0002400	87.46	gold quality
bronchial epithelial cell	CL:0002328	85.71	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.26	gold quality
bronchus	UBERON:0002185	85.20	gold quality
pigmented layer of retina	UBERON:0001782	84.89	gold quality
popliteal artery	UBERON:0002250	84.77	gold quality
tibial artery	UBERON:0007610	84.76	gold quality
artery	UBERON:0001637	84.32	gold quality
thoracic mammary gland	UBERON:0005200	83.95	gold quality
left coronary artery	UBERON:0001626	83.84	gold quality
mammary gland	UBERON:0001911	83.84	gold quality
coronary artery	UBERON:0001621	82.85	gold quality
gall bladder	UBERON:0002110	82.83	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	1089.48
E-GEOD-93593	yes	14.54
E-MTAB-7303	no	65.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

211 targeting CRISPLD1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588

Literature-anchored findings (GeneRIF, showing 2)

• These novel findings suggest that CRISPLD1 plays a role in Nonsyndromic cleft lip and palate (NSCLP) through the interaction with CRISPLD2 and folate pathway genes. (PMID:21254358)
• CRISPLD1: a novel conserved target in the transition to human heart failure; findings provide new pathophysiological data on Ca(2+) regulation in the transition to failure and novel candidate genes with promising potential for therapeutic interventions (PMID:32146539)

Cross-species orthologs

47 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000046021
mus_musculus	Crispld1	ENSMUSG00000025776
rattus_norvegicus	Crispld1	ENSRNOG00000017773
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), GLIPR2 (ENSG00000122694), CRISP2 (ENSG00000124490), CRISP1 (ENSG00000124812), PI15 (ENSG00000137558), GLIPR1 (ENSG00000139278), CLEC18B (ENSG00000140839), CLEC18A (ENSG00000157322), CLEC18C (ENSG00000157335), GLIPR1L1 (ENSG00000173401), GLIPR1L2 (ENSG00000180481)

Protein

Protein identifiers

Cysteine-rich secretory protein LCCL domain-containing 1 — Q9H336 (reviewed: Q9H336)

Alternative names: CocoaCrisp, Cysteine-rich secretory protein 10, LCCL domain-containing cysteine-rich secretory protein 1, Trypsin inhibitor Hl

All UniProt accessions (3): B7Z8V9, E5RJS4, Q9H336

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the CRISP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H336-1	1	yes
Q9H336-2	2

RefSeq proteins (3): NP_001273706, NP_001273707, NP_113649* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001283	CRISP-related	Family
IPR004043	LCCL	Domain
IPR014044	CAP_dom	Domain
IPR018244	Allrgn_V5/Tpx1_CS	Conserved_site
IPR035940	CAP_sf	Homologous_superfamily
IPR036609	LCCL_sf	Homologous_superfamily
IPR051957	CRISP-LCCL_domain	Family

Pfam: PF00188, PF03815

UniProt features (14 total): disulfide bond 4, domain 3, splice variant 2, signal peptide 1, chain 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H336-F1	80.72	0.54

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 (4): 422–445, 295–313, 317–337, 396–418

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 154 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_BODY_MORPHOGENESIS, GOBP_FACE_DEVELOPMENT, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, GOBP_HEAD_DEVELOPMENT, FUJII_YBX1_TARGETS_DN, MYB_Q3, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, CTTTGTA_MIR524, MYB_Q5_01, GOBP_HEAD_MORPHOGENESIS, VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_UP, GOBP_HOMEOSTATIC_PROCESS, GOBP_HOMEOSTASIS_OF_NUMBER_OF_CELLS

GO Biological Process (2): face morphogenesis (GO:0060325), hematopoietic stem cell homeostasis (GO:0061484)

GO Molecular Function (0):

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure morphogenesis	1
head morphogenesis	1
face development	1
homeostasis of number of cells	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

700 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRISPLD1	SEC22C	Q9BRL7	470
CRISPLD1	RUNDC3B	Q96NL0	449
CRISPLD1	RFLNA	Q6ZTI6	415
CRISPLD1	ZNRD2	O60232	414
CRISPLD1	GDAP1	Q8TB36	393
CRISPLD1	FAM169BP	Q8N8A8	383
CRISPLD1	ASB7	Q9H672	376
CRISPLD1	CILP2	Q8IUL8	359
CRISPLD1	ARMCX1	Q9P291	359
CRISPLD1	ITGBL1	O95965	352
CRISPLD1	TMTC2	Q8N394	352
CRISPLD1	HGSNAT	Q68CP4	343
CRISPLD1	SH3YL1	Q96HL8	342
CRISPLD1	INPP5K	Q9BT40	337
CRISPLD1	PBLD	P30039	332

IntAct

5 interactions, top by confidence:

A	B	Type	Score
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): CRISPLD1 (Affinity Capture-MS), CRISPLD1 (Affinity Capture-MS), CRISPLD1 (Affinity Capture-MS), CRISPLD1 (Affinity Capture-MS), CRISPLD1 (Affinity Capture-MS), CRISPLD1 (Affinity Capture-RNA), CRISPLD1 (Cross-Linking-MS (XL-MS)), CRISPLD1 (Co-fractionation), CRISPLD1 (Co-fractionation)

ESM2 similar proteins: A0A0N9E2K8, A0A1D5NSK0, A0A8M9PFP2, G5ECS8, G5EFD9, O15072, O18767, O43909, O60882, O62806, O77656, O93470, P07152, P22003, P23097, P28825, P29788, P33435, P49003, P57748, P79287, Q10835, Q11005, Q14703, Q16819, Q16820, Q19791, Q24025, Q3U435, Q568B8, Q61847, Q64230, Q6GQB9, Q6NP60, Q8CGD2, Q8K3F2, Q8N119, Q8R4K8, Q8VDA1, Q90YC2

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

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	74
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1527442	GRCh37/hg19 8q21.11-21.13(chr8:75197438-81685526)	Pathogenic
57417	GRCh38/hg38 8q21.11-21.13(chr8:73519300-82655582)x1	Pathogenic
253364	GRCh37/hg19 8q13.3-21.13(chr8:70971013-82019151)x3	Likely pathogenic

SpliceAI

1780 predictions. Top by Δscore:

Variant	Effect	Δscore
8:74984918:GAG:G	donor_gain	1.0000
8:74984920:GGTAA:G	donor_loss	1.0000
8:74984922:T:G	donor_loss	1.0000
8:75012549:A:T	donor_gain	1.0000
8:75014103:G:GG	donor_gain	1.0000
8:75016563:A:AG	acceptor_gain	1.0000
8:75016563:AGAAG:A	acceptor_gain	1.0000
8:75016564:G:GG	acceptor_gain	1.0000
8:75016564:GA:G	acceptor_gain	1.0000
8:75016564:GAA:G	acceptor_gain	1.0000
8:75016564:GAAGG:G	acceptor_gain	1.0000
8:75016701:AATGT:A	donor_gain	1.0000
8:75016702:ATGT:A	donor_gain	1.0000
8:75016704:GT:G	donor_gain	1.0000
8:75016706:G:GG	donor_gain	1.0000
8:75016879:A:AG	acceptor_gain	1.0000
8:75016880:G:GG	acceptor_gain	1.0000
8:75017042:TTTAG:T	acceptor_loss	1.0000
8:75017044:TAG:T	acceptor_loss	1.0000
8:75017045:A:AT	acceptor_loss	1.0000
8:75017046:GGT:G	acceptor_gain	1.0000
8:75017046:GGTAC:G	acceptor_gain	1.0000
8:75017110:AATG:A	donor_gain	1.0000
8:75017111:ATG:A	donor_gain	1.0000
8:75017112:TG:T	donor_gain	1.0000
8:75017112:TGGT:T	donor_loss	1.0000
8:75017113:GG:G	donor_gain	1.0000
8:75017114:G:GG	donor_gain	1.0000
8:75017115:TAAGT:T	donor_loss	1.0000
8:75017316:CAA:C	acceptor_loss	1.0000

AlphaMissense

3301 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:75012438:G:C	W88C	1.000
8:75012438:G:T	W88C	1.000
8:75012487:T:A	W105R	1.000
8:75012487:T:C	W105R	1.000
8:75012489:G:C	W105C	1.000
8:75012489:G:T	W105C	1.000
8:75012527:A:C	Q118P	1.000
8:75012531:T:A	N119K	1.000
8:75012531:T:G	N119K	1.000
8:75012921:T:A	W137R	1.000
8:75012921:T:C	W137R	1.000
8:75012923:G:C	W137C	1.000
8:75012923:G:T	W137C	1.000
8:75013005:T:A	C165S	1.000
8:75013006:G:A	C165Y	1.000
8:75013006:G:C	C165S	1.000
8:75013007:T:G	C165W	1.000
8:75013993:T:A	W173R	1.000
8:75013993:T:C	W173R	1.000
8:75013995:G:C	W173C	1.000
8:75013995:G:T	W173C	1.000
8:75014014:G:T	G180C	1.000
8:75014017:T:A	C181S	1.000
8:75014017:T:C	C181R	1.000
8:75014018:G:C	C181S	1.000
8:75014032:T:A	C186S	1.000
8:75014033:G:C	C186S	1.000
8:75014034:T:G	C186W	1.000
8:75014081:T:C	L202P	1.000
8:75014086:T:A	C204S	1.000

dbSNP variants (sampled 300 via entrez): RS1000016778 (8:74992032 C>A), RS1000075450 (8:74999300 C>A,G), RS1000168881 (8:75029106 C>G), RS1000170029 (8:75008739 A>G), RS1000281821 (8:75018436 G>C), RS1000310239 (8:75025225 T>C), RS1000369929 (8:75015673 C>T), RS1000430691 (8:75011723 C>G), RS1000485641 (8:75015890 G>C), RS1000590502 (8:74986354 A>C), RS1000592469 (8:75009325 A>G), RS1000792387 (8:75022823 C>T), RS1000800000 (8:75002992 T>C), RS1000802610 (8:74993097 A>G), RS1000874572 (8:74993419 T>C)

Disease associations

OMIM: gene MIM:621340 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004137_17	Optic cup area	1.000000e-08
GCST004137_33	Optic cup area	2.000000e-06
GCST006406_4	Cognitive flexibility	5.000000e-06
GCST007096_146	Pulse pressure	4.000000e-09
GCST011037_5	Parkinson’s disease progression (cognitive)	4.000000e-06
GCST012227_30	Hip circumference adjusted for BMI	2.000000e-10
GCST90020028_308	Hip circumference adjusted for BMI	1.000000e-08
GCST90020029_85	Waist circumference adjusted for body mass index	1.000000e-08
GCST90020029_86	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0009332	executive function measurement
EFO:0005763	pulse pressure measurement
EFO:0008336	disease progression measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
terbufos	increases methylation	1
perfluorooctanoic acid	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
acyline	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Calcitriol	increases expression	1
Citrulline	increases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Estradiol	increases expression	1
Ethinyl Estradiol	increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Parathion	increases methylation	1

Clinical trials (associated diseases)

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