CRIP3

Summary

CRIP3 (cysteine rich protein 3, HGNC:17751) is a protein-coding gene on chromosome 6p21.1, encoding Cysteine-rich protein 3 (Q6Q6R5).

Predicted to enable metal ion binding activity. Predicted to act upstream of or within T cell proliferation. Predicted to be located in cytoplasm.

Source: NCBI Gene 401262 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_206922

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17751
Approved symbol	CRIP3
Name	cysteine rich protein 3
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	TLP-A, bA480N24.2, TLP
Ensembl gene	ENSG00000146215
Ensembl biotype	protein_coding
Entrez	401262

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 18 protein_coding, 3 retained_intron

ENST00000274990, ENST00000372569, ENST00000416431, ENST00000451294, ENST00000477866, ENST00000485819, ENST00000487744, ENST00000875330, ENST00000875331, ENST00000875332, ENST00000875333, ENST00000917954, ENST00000917955, ENST00000917956, ENST00000917957, ENST00000917958, ENST00000917959, ENST00000917960, ENST00000917961, ENST00000917962, ENST00000917963

RefSeq mRNA: 2 — MANE Select: NM_206922 NM_001366068, NM_206922

CCDS: CCDS4894

Canonical transcript exons

ENST00000372569 — 8 exons

Exon	Start	End
ENSE00000974499	43308315	43308409
ENSE00000974501	43307612	43307743
ENSE00000974502	43306446	43306517
ENSE00000974503	43306219	43306313
ENSE00001458118	43305472	43305875
ENSE00003545360	43307839	43307896
ENSE00003570712	43306067	43306124
ENSE00003902020	43308750	43308826

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 95.03.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1956 / max 53.0668, expressed in 275 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73675	1.0381	246
73676	0.1574	90

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	95.03	gold quality
right testis	UBERON:0004534	92.37	gold quality
left testis	UBERON:0004533	92.14	gold quality
cerebellar hemisphere	UBERON:0002245	90.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.00	gold quality
cerebellar cortex	UBERON:0002129	89.98	gold quality
testis	UBERON:0000473	88.30	gold quality
cerebellum	UBERON:0002037	88.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.70	gold quality
right lobe of liver	UBERON:0001114	85.23	gold quality
granulocyte	CL:0000094	85.16	gold quality
heart left ventricle	UBERON:0002084	84.88	gold quality
cardiac ventricle	UBERON:0002082	84.43	gold quality
nucleus accumbens	UBERON:0001882	83.88	gold quality
right frontal lobe	UBERON:0002810	81.96	gold quality
putamen	UBERON:0001874	81.85	gold quality
caudate nucleus	UBERON:0001873	81.47	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.34	gold quality
amygdala	UBERON:0001876	81.14	gold quality
spleen	UBERON:0002106	80.55	gold quality
anterior cingulate cortex	UBERON:0009835	79.51	gold quality
hypothalamus	UBERON:0001898	79.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.06	gold quality
lymph node	UBERON:0000029	77.05	gold quality
heart	UBERON:0000948	76.87	gold quality
sperm	CL:0000019	76.36	silver quality
cortical plate	UBERON:0005343	76.34	gold quality
brain	UBERON:0000955	76.09	gold quality
liver	UBERON:0002107	75.49	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	75.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.54

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• TLP-mediated global transcriptional repression after double-strand DNA breaks slows down DNA repair and induces apoptosis. (PMID:30890736)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	crip3	ENSDARG00000043395
mus_musculus	Crip3	ENSMUSG00000023968
rattus_norvegicus	Crip3	ENSRNOG00000018613

Paralogs (20): FHL1 (ENSG00000022267), LMO3 (ENSG00000048540), LHX5 (ENSG00000089116), ZFHX4 (ENSG00000091656), LHX2 (ENSG00000106689), LHX6 (ENSG00000106852), LHX3 (ENSG00000107187), LHX4 (ENSG00000121454), LMO2 (ENSG00000135363), ZFHX2 (ENSG00000136367), LMX1B (ENSG00000136944), ZFHX3 (ENSG00000140836), LMO4 (ENSG00000143013), LHX9 (ENSG00000143355), LHX8 (ENSG00000162624), LMX1A (ENSG00000162761), LMO1 (ENSG00000166407), CRIP2 (ENSG00000182809), CRIP1 (ENSG00000213145), LHX1 (ENSG00000273706)

Protein

Protein identifiers

Cysteine-rich protein 3 — Q6Q6R5 (reviewed: Q6Q6R5)

Alternative names: Chromosome 6 LIM domain only protein

All UniProt accessions (3): Q6Q6R5, H0Y7Q9, Q5T045

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in most tissues, but not in skeletal muscle.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6Q6R5-1	1, C	yes
Q6Q6R5-2	2, B
Q6Q6R5-3	3, A
Q6Q6R5-4	4, D

RefSeq proteins (2): NP_001352997, NP_996805* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain

Pfam: PF00412

UniProt features (9 total): splice variant 3, domain 2, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6Q6R5-F1	74.81	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 44 (showing top): GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_DN, STK33_SKM_DN, ZNF322_TARGET_GENES, MIR4731_5P, GSE11057_EFF_MEM_VS_CENT_MEM_CD4_TCELL_DN, MIR423_5P, MIR3184_5P, MIR6759_3P, GSE12366_NAIVE_VS_MEMORY_BCELL_UP, MIR1911_5P, BLANCO_MELO_RESPIRATORY_SYNCYTIAL_VIRUS_INFECTION_A594_CELLS_DN, GSE15750_WT_VS_TRAF6KO_DAY10_EFF_CD8_TCELL_UP, HAY_BONE_MARROW_DENDRITIC_CELL, GSE17721_POLYIC_VS_CPG_16H_BMDC_UP, WRNIP1_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): metal ion binding (GO:0046872), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cation binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRIP3	TIRAP	P58753	576
CRIP3	HOXD8	P13378	538
CRIP3	MYD88	P78397	523
CRIP3	HOXD3	P31249	521
CRIP3	HTRA1	Q92743	479
CRIP3	SCO1	O75880	467
CRIP3	TGFB2	P08112	432
CRIP3	COA6	Q5JTJ3	395
CRIP3	H0YIS7	H0YIS7	393
CRIP3	TMEM128	Q5BJH2	391
CRIP3	TMEM179	Q6ZVK1	367
CRIP3	CIMIP2A	Q6J272	322
CRIP3	SARM1	Q6SZW1	317
CRIP3	SH2D4B	Q5SQS7	316
CRIP3	OR2A7	Q96R45	307

IntAct

1 interactions, top by confidence:

BioGRID (2): CRIP3 (Two-hybrid), FHL3 (Two-hybrid)

ESM2 similar proteins: A2YEZ6, A3BDI8, E0X9N4, O60711, O70209, O70400, O80839, P29675, P36201, P47226, P52943, P53777, Q0VFX8, Q16975, Q1LZA7, Q21192, Q24400, Q3EA33, Q3SX40, Q3SYZ8, Q3TJD7, Q4KM31, Q500W4, Q53GG5, Q5R7Y1, Q66HS7, Q679P3, Q6GLJ6, Q6INU3, Q6P7E4, Q6Q6R3, Q6Q6R5, Q6QGC0, Q7Y1W9, Q852K5, Q8BGB5, Q8H0X0, Q94JX5, Q99N69, Q9BIW5

Diamond homologs: A8DZE6, E1BKA3, F1MF74, F1QH17, F1QWK4, G3MWR8, O04193, O14014, O80839, P21291, P29675, P34416, P36201, P47875, P50238, P50460, P50461, P50462, P50463, P52943, P53410, P53777, P63254, P63255, P67966, P67967, P97314, P97315, Q04584, Q05158, Q0VFX8, Q13642, Q14192, Q16527, Q1ECF5, Q24400, Q2KI95, Q32LE9, Q3MHY1, Q4U0T9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2400 predictions. Top by Δscore:

Variant	Effect	Δscore
6:43299885:T:TA	acceptor_gain	1.0000
6:43299890:T:A	acceptor_gain	1.0000
6:43299891:G:A	acceptor_gain	1.0000
6:43299896:A:AG	acceptor_gain	1.0000
6:43299897:G:GG	acceptor_gain	1.0000
6:43301690:GTG:G	donor_gain	1.0000
6:43301698:G:GT	donor_gain	1.0000
6:43302761:CAGGT:C	donor_loss	1.0000
6:43302762:AGGT:A	donor_loss	1.0000
6:43302763:GG:G	donor_loss	1.0000
6:43302764:GTGA:G	donor_loss	1.0000
6:43302765:T:G	donor_loss	1.0000
6:43304669:A:AG	acceptor_gain	1.0000
6:43304670:G:GG	acceptor_gain	1.0000
6:43306123:TG:T	acceptor_gain	1.0000
6:43306131:C:CT	acceptor_gain	1.0000
6:43306314:C:CC	acceptor_gain	1.0000
6:43307610:A:AC	donor_gain	1.0000
6:43307611:C:CC	donor_gain	1.0000
6:43307611:CTTTT:C	donor_gain	1.0000
6:43308514:T:TA	donor_gain	1.0000
6:43299894:CCA:C	acceptor_loss	0.9900
6:43299895:CA:C	acceptor_loss	0.9900
6:43299896:A:T	acceptor_loss	0.9900
6:43299897:G:A	acceptor_loss	0.9900
6:43299897:GA:G	acceptor_gain	0.9900
6:43299897:GAGC:G	acceptor_gain	0.9900
6:43299897:GAGCT:G	acceptor_gain	0.9900
6:43299988:T:G	donor_gain	0.9900
6:43300063:TCTGG:T	donor_loss	0.9900

AlphaMissense

1340 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:43306454:A:T	V131D	0.996
6:43306282:C:A	W144C	0.995
6:43306282:C:G	W144C	0.995
6:43306109:A:C	Y171D	0.994
6:43306263:A:G	C151R	0.994
6:43306476:A:G	C124R	0.994
6:43306284:A:G	W144R	0.993
6:43306284:A:T	W144R	0.993
6:43307849:A:C	F62L	0.993
6:43307849:A:T	F62L	0.993
6:43307851:A:G	F62L	0.993
6:43308378:C:A	W25C	0.993
6:43308378:C:G	W25C	0.993
6:43308380:A:G	W25R	0.993
6:43308380:A:T	W25R	0.993
6:43306077:A:C	F181L	0.992
6:43306077:A:T	F181L	0.992
6:43306079:A:G	F181L	0.992
6:43306253:C:G	C154S	0.992
6:43306254:A:T	C154S	0.992
6:43306262:C:G	C151S	0.992
6:43306263:A:T	C151S	0.992
6:43306094:A:G	C176R	0.991
6:43306104:G:C	C172W	0.991
6:43306281:G:C	H145D	0.991
6:43307881:A:C	Y52D	0.991
6:43308359:A:G	C32R	0.991
6:43306268:A:G	L149P	0.990
6:43306279:G:C	H145Q	0.990
6:43306279:G:T	H145Q	0.990

dbSNP variants (sampled 300 via entrez): RS1002130301 (6:43306679 T>C), RS1002162974 (6:43306956 C>T), RS1002798038 (6:43309582 G>A), RS1002870266 (6:43309870 A>T), RS1003203414 (6:43308489 G>A), RS1004761361 (6:43306088 C>A,T), RS1004788366 (6:43309065 C>T), RS1004827097 (6:43310330 T>C), RS1005178609 (6:43305268 A>G), RS1005250663 (6:43305540 C>A), RS1005501185 (6:43310324 C>A,T), RS1006728651 (6:43305759 A>G,T), RS1007581094 (6:43308528 G>A,C), RS1008585250 (6:43306831 G>GCCA), RS1008846918 (6:43307235 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST004521_164	Autism spectrum disorder or schizophrenia	3.000000e-08
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
GCST006187_17	Diastolic blood pressure (cigarette smoking interaction)	1.000000e-10
GCST006188_32	Systolic blood pressure (cigarette smoking interaction)	8.000000e-21
GCST007096_193	Pulse pressure	3.000000e-06
GCST007099_135	Systolic blood pressure	1.000000e-09
GCST007703_139	Systolic blood pressure	4.000000e-10
GCST007704_105	Diastolic blood pressure	1.000000e-06
GCST007705_69	Pulse pressure	4.000000e-06
GCST007706_92	Mean arterial pressure	4.000000e-09
GCST007707_66	Hypertension	1.000000e-06
GCST008058_90	Estimated glomerular filtration rate	1.000000e-20
GCST008059_82	Estimated glomerular filtration rate	2.000000e-20
GCST008839_248	Height	4.000000e-08
GCST008899_1	Adult hearing difficulty	6.000000e-21
GCST012227_9	Hip circumference adjusted for BMI	2.000000e-08
GCST012442_37	Age-related hearing impairment	1.000000e-17

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006340	mean arterial pressure
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, decreases expression	2
Aflatoxin B1	decreases expression	2
propionaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	decreases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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