Mutagenetix > Incidental Mutation

Incidental Mutation 'R0030:Crip1'

15282

Institutional Source

Beutler Lab

Gene Symbol

Crip1

Ensembl Gene

ENSMUSG00000006360

Gene Name

cysteine-rich protein 1

Synonyms

CRP1, Crip

MMRRC Submission

038324-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.350) question?

Stock #

R0030 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

113115632-113117499 bp(+) (GRCm39)

Type of Mutation

critical splice donor site (1 bp from exon)

DNA Base Change (assembly)

G to A at 113116996 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000143680 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000006523] [ENSMUST00000049271] [ENSMUST00000196755] [ENSMUST00000200553] [ENSMUST00000199089] [ENSMUST00000200522]

AlphaFold

P63254

Predicted Effect

probably null
Transcript: ENSMUST00000006523

SMART Domains

Protein: ENSMUSP00000006523
Gene: ENSMUSG00000006360

Domain	Start	End	E-Value	Type
LIM	3	55	2e-14	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000049271

SMART Domains

Protein: ENSMUSP00000035351
Gene: ENSMUSG00000037466

Domain	Start	End	E-Value	Type
low complexity region	2	21	N/A	INTRINSIC
Pfam:DUF4509	41	221	4.8e-65	PFAM
low complexity region	233	245	N/A	INTRINSIC
Pfam:DUF4510	258	418	3.1e-73	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000196505

Predicted Effect

probably benign
Transcript: ENSMUST00000196755

SMART Domains

Protein: ENSMUSP00000143431
Gene: ENSMUSG00000037466

Domain	Start	End	E-Value	Type
low complexity region	1	20	N/A	INTRINSIC
Pfam:DUF4509	40	138	4.1e-32	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000196932

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000198072

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000198597

Predicted Effect

probably null
Transcript: ENSMUST00000200553

SMART Domains

Protein: ENSMUSP00000143680
Gene: ENSMUSG00000006360

Domain	Start	End	E-Value	Type
LIM	3	55	2e-14	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000198909

Predicted Effect

probably null
Transcript: ENSMUST00000199089

SMART Domains

Protein: ENSMUSP00000142803
Gene: ENSMUSG00000006360

Domain	Start	End	E-Value	Type
LIM	54	106	9.5e-17	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000199382

Predicted Effect

probably benign
Transcript: ENSMUST00000200522

Meta Mutation Damage Score

0.9493

Coding Region Coverage

1x: 78.5%
3x: 68.6%
10x: 42.5%
20x: 22.6%

Validation Efficiency

97% (72/74)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Cysteine-rich intestinal protein (CRIP) belongs to the LIM/double zinc finger protein family, members of which include cysteine- and glycine-rich protein-1 (CSRP1; MIM 123876), rhombotin-1 (RBTN1; MIM 186921), rhombotin-2 (RBTN2; MIM 180385), and rhombotin-3 (RBTN3; MIM 180386). CRIP may be involved in intestinal zinc transport (Hempe and Cousins, 1991 [PubMed 1946385]).[supplied by OMIM, Mar 2008]

Allele List at MGI

All alleles(8) : Targeted(2) Gene trapped(6)

Other mutations in this stock

Total: 30 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aebp2	A	C	6: 140,583,473 (GRCm39)	S316R	probably damaging	Het
Brwd1	A	G	16: 95,822,456 (GRCm39)	S1250P	probably damaging	Het
Cacna1s	T	C	1: 136,022,727 (GRCm39)		probably null	Het
Cass4	G	T	2: 172,269,762 (GRCm39)	E617*	probably null	Het
Cct4	T	C	11: 22,951,357 (GRCm39)		probably benign	Het
Cdh20	C	T	1: 110,065,798 (GRCm39)	Q691*	probably null	Het
Dnah5	A	T	15: 28,451,663 (GRCm39)	D4367V	probably benign	Het
Dock3	A	G	9: 106,789,512 (GRCm39)	V1514A	possibly damaging	Het
Eps15l1	A	G	8: 73,126,894 (GRCm39)	S646P	probably benign	Het
Faap24	A	T	7: 35,092,285 (GRCm39)	F211I	probably damaging	Het
Flrt3	A	T	2: 140,502,237 (GRCm39)	Y464N	probably damaging	Het
Foxi2	A	G	7: 135,013,345 (GRCm39)	T192A	probably damaging	Het
Gm7298	T	A	6: 121,751,009 (GRCm39)	F695L	probably benign	Het
Ifnk	T	G	4: 35,152,489 (GRCm39)	V139G	probably benign	Het
Kif18a	A	T	2: 109,163,663 (GRCm39)	I671L	probably benign	Het
Lcn10	T	C	2: 25,575,093 (GRCm39)	F154L	probably damaging	Het
Med12l	T	G	3: 59,156,076 (GRCm39)	L1198R	probably damaging	Het
Mmp23	G	A	4: 155,735,768 (GRCm39)	R268*	probably null	Het
Mrps30	T	C	13: 118,519,531 (GRCm39)	D298G	possibly damaging	Het
Myh7	T	A	14: 55,229,427 (GRCm39)	T124S	probably benign	Het
Odf4	T	A	11: 68,817,767 (GRCm39)	E9D	probably benign	Het
Ptchd4	T	A	17: 42,627,999 (GRCm39)	C153*	probably null	Het
Scp2	T	A	4: 107,964,887 (GRCm39)		probably null	Het
Slc16a10	A	G	10: 39,952,819 (GRCm39)	V225A	probably benign	Het
Slc66a1	A	G	4: 139,033,764 (GRCm39)	S52P	probably damaging	Het
Tbk1	A	G	10: 121,397,529 (GRCm39)	V381A	probably benign	Het
Tdrd6	T	C	17: 43,937,482 (GRCm39)	K1189E	possibly damaging	Het
Ttc39a	C	A	4: 109,280,170 (GRCm39)	H151N	probably benign	Het
Ush2a	C	T	1: 188,554,854 (GRCm39)	T3544M	possibly damaging	Het
Vnn1	A	G	10: 23,776,744 (GRCm39)	H365R	probably benign	Het

Other mutations in Crip1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00469:Crip1	APN	12	113,115,755 (GRCm39)	missense	probably damaging	1.00
IGL00562:Crip1	APN	12	113,117,232 (GRCm39)	splice site	probably null
IGL00563:Crip1	APN	12	113,117,232 (GRCm39)	splice site	probably null
R1879:Crip1	UTSW	12	113,116,952 (GRCm39)	missense	probably damaging	1.00
R4542:Crip1	UTSW	12	113,117,109 (GRCm39)	missense	probably damaging	1.00
R5918:Crip1	UTSW	12	113,117,287 (GRCm39)	splice site	probably null

Protein Function and Prediction

Cysteine-rich intestinal protein (CRIP) belongs to the LIM/double zinc finger protein family of proteins that are proposed to be involved in cellular growth and differentiation (1;2). CRIP binds zinc during transmucosal zinc transport (3). CRIP1 is proposed to influence various cellular and immunological signalling pathways involved in cellular differentiation, protein-protein interactions during transcription, immune response, and cytokine expression (1;2;4). CRIP1 has also been proposed to be a biomarker for breast cancer and precursor lesions (5) as well as in colorectal, cervical and prostatic cancer; downregulation of CRIP1 is observed in pancreatic carcinoma (6-8). Overexpression of CRIP1 results in significantly shorter overall survival in patients with gastric cancer (9).

Expression/Localization

In the rat, Crip is highly expressed in the small intestine, with lower levels in adult heart and spleen (1;10).

Background

CRIP transgenic mice challenged with lipopolysaccharide (LPS) had lower serum concentrations of interferon-gamma and tumor necrosis factor-alpha; IL-6 and IL-10 were higher (1;2).

References

1. Cousins, R. J., and Lanningham-Foster, L. (2000) Regulation of Cysteine-Rich Intestinal Protein, a Zinc Finger Protein, by Mediators of the Immune Response. J Infect Dis. 182 Suppl 1, S81-4.

2. Lanningham-Foster, L., Green, C. L., Langkamp-Henken, B., Davis, B. A., Nguyen, K. T., Bender, B. S., and Cousins, R. J. (2002) Overexpression of CRIP in Transgenic Mice Alters Cytokine Patterns and the Immune Response. Am J Physiol Endocrinol Metab. 282, E1197-203.

3. Hempe, J. M., and Cousins, R. J. (1991) Cysteine-Rich Intestinal Protein Binds Zinc during Transmucosal Zinc Transport. Proc Natl Acad Sci U S A. 88, 9671-9674.

4. Baumhoer, D., Elsner, M., Smida, J., Zillmer, S., Rauser, S., Schoene, C., Balluff, B., Bielack, S., Jundt, G., Walch, A., and Nathrath, M. (2011) CRIP1 Expression is Correlated with a Favorable Outcome and Less Metastases in Osteosarcoma Patients. Oncotarget. 2, 970-975.

5. Ma, X. J., Salunga, R., Tuggle, J. T., Gaudet, J., Enright, E., McQuary, P., Payette, T., Pistone, M., Stecker, K., Zhang, B. M., Zhou, Y. X., Varnholt, H., Smith, B., Gadd, M., Chatfield, E., Kessler, J., Baer, T. M., Erlander, M. G., and Sgroi, D. C. (2003) Gene Expression Profiles of Human Breast Cancer Progression. Proc Natl Acad Sci U S A. 100, 5974-5979.

6. Wang, Q., Williamson, M., Bott, S., Brookman-Amissah, N., Freeman, A., Nariculam, J., Hubank, M. J., Ahmed, A., and Masters, J. R. (2007) Hypomethylation of WNT5A, CRIP1 and S100P in Prostate Cancer. Oncogene. 26, 6560-6565.

7. Terris, B., Blaveri, E., Crnogorac-Jurcevic, T., Jones, M., Missiaglia, E., Ruszniewski, P., Sauvanet, A., and Lemoine, N. R. (2002) Characterization of Gene Expression Profiles in Intraductal Papillary-Mucinous Tumors of the Pancreas. Am J Pathol. 160, 1745-1754.

8. Chen, Y., Miller, C., Mosher, R., Zhao, X., Deeds, J., Morrissey, M., Bryant, B., Yang, D., Meyer, R., Cronin, F., Gostout, B. S., Smith-McCune, K., and Schlegel, R. (2003) Identification of Cervical Cancer Markers by cDNA and Tissue Microarrays. Cancer Res. 63, 1927-1935.

9. Balluff, B., Rauser, S., Meding, S., Elsner, M., Schone, C., Feuchtinger, A., Schuhmacher, C., Novotny, A., Jutting, U., Maccarrone, G., Sarioglu, H., Ueffing, M., Braselmann, H., Zitzelsberger, H., Schmid, R. M., Hofler, H., Ebert, M. P., and Walch, A. (2011) MALDI Imaging Identifies Prognostic Seven-Protein Signature of Novel Tissue Markers in Intestinal-Type Gastric Cancer. Am J Pathol. 179, 2720-2729.

10. Tsui, S. K., Yam, N. Y., Lee, C. Y., and Waye, M. M. (1994) Isolation and Characterization of a cDNA that Codes for a LIM-Containing Protein which is Developmentally Regulated in Heart. Biochem Biophys Res Commun. 205, 497-505.

Posted On

2012-12-17

Science Writer

Anne Murray