CSRP2

Summary

CSRP2 (cysteine and glycine rich protein 2, HGNC:2470) is a protein-coding gene on chromosome 12q21.2, encoding Cysteine and glycine-rich protein 2 (Q16527). Drastically down-regulated in response to PDGF-BB or cell injury, that promote smooth muscle cell proliferation and dedifferentiation.

CSRP2 is a member of the CSRP family of genes, encoding a group of LIM domain proteins, which may be involved in regulatory processes important for development and cellular differentiation. CRP2 contains two copies of the cysteine-rich amino acid sequence motif (LIM) with putative zinc-binding activity, and may be involved in regulating ordered cell growth. Other genes in the family include CSRP1 and CSRP3. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1466 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 25 total
• GTEx eGene: eQTL in 29 tissues, sQTL in 19 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.01 (unconstrained)
• MANE Select transcript: NM_001321

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2470
Approved symbol	CSRP2
Name	cysteine and glycine rich protein 2
Location	12q21.2
Locus type	gene with protein product
Status	Approved
Aliases	SmLIM, CRP2, LMO5
Ensembl gene	ENSG00000175183
Ensembl biotype	protein_coding
OMIM	601871
Entrez	1466

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 31 protein_coding, 5 nonsense_mediated_decay, 3 retained_intron

MANE Select: ENST00000311083

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 2

ENST00000311083, ENST00000546966, ENST00000547435, ENST00000547557, ENST00000548783, ENST00000551725, ENST00000552330, ENST00000909815, ENST00000909816, ENST00000909817, ENST00000909818, ENST00000909819, ENST00000909820, ENST00000909821, ENST00000909822, ENST00000919906, ENST00000919907, ENST00000919908, ENST00000919909, ENST00000919910, ENST00000919911, ENST00000919912, ENST00000919913, ENST00000919914, ENST00000919915, ENST00000919916, ENST00000965133, ENST00000975895, ENST00001055349, ENST00001072736, ENST00001072737, ENST00001072739, ENST00001072741, ENST00001072744, ENST00001072747, ENST00001072750, ENST00001093731, ENST00001131167, ENST00001141719

RefSeq mRNA: 9 — MANE Select: NM_001321 NM_001300965, NM_001321, NM_001413535, NM_001413537, NM_001413538, NM_001413539, NM_001413540, NM_001413541, NM_001413542

CCDS: CCDS9015

Canonical transcript exons

ENST00000311083 — 6 exons

Exon	Start	End
ENSE00001210521	76860284	76860413
ENSE00001210527	76863176	76863344
ENSE00001210540	76866149	76866261
ENSE00002337743	76878938	76879019
ENSE00002397508	76858709	76859028
ENSE00003587346	76859547	76859640

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.6958 / max 850.8149, expressed in 1455 samples.

Highest expression (Bgee): oocyte, secondary oocyte, cervix squamous epithelium, cortical plate, blood vessel layer.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CSRP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 19 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 48 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	sqtl	1.5e-51	-0.59	12:76867119:G:A
Adipose Subcutaneous	sqtl	8.7e-31	+0.55	12:76824094:T:A
Brain Caudate basal ganglia	eqtl	2.1e-27	+0.64	12:76921493:C:T
Brain Putamen basal ganglia	eqtl	2.6e-25	+0.72	12:76921493:C:T
Artery Aorta	sqtl	1.9e-24	+0.55	12:76824088:G:A
Brain Nucleus accumbens basal ganglia	eqtl	8.0e-23	+0.62	12:76919914:C:T
Esophagus Mucosa	sqtl	3.9e-16	+0.47	12:76816717:G:T
Esophagus Mucosa	eqtl	1.3e-14	-0.33	12:76881576:A:G
Skin Sun Exposed Lower leg	sqtl	2.4e-13	+0.45	12:76819987:A:C
Artery Tibial	eqtl	1.1e-11	-0.37	12:76905618:T:A
Nerve Tibial	sqtl	8.5e-11	+0.40	12:76845640:AAAAT:A
Adipose Visceral Omentum	sqtl	2.7e-10	+0.39	12:76860731:C:T
Brain Cortex	eqtl	8.9e-10	-0.41	12:77042264:T:C
Colon Sigmoid	eqtl	9.1e-10	-0.34	12:76860731:C:T
Breast Mammary Tissue	sqtl	9.6e-10	+0.39	12:76768533:G:T
Lung	sqtl	9.8e-10	+0.25	12:76835787:C:T
Esophagus Muscularis	sqtl	1.2e-09	+0.43	12:76845640:AAAAT:A
Artery Coronary	sqtl	2.2e-08	+0.61	12:76836978:C:A
Esophagus Gastroesophageal Junction	sqtl	4.1e-08	+0.47	12:76861798:T:C
Brain Spinal cord cervical c-1	eqtl	7.5e-08	+0.45	12:76919914:C:T

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
132231	19.6057	1455
132227	0.0318	5
132229	0.0282	10
132230	0.0257	7
132228	0.0044	2

Top tissues by expression

showing 100 of 301 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.86	gold quality
secondary oocyte	CL:0000655	99.82	gold quality
cervix squamous epithelium	UBERON:0006922	99.57	gold quality
cortical plate	UBERON:0005343	99.51	gold quality
blood vessel layer	UBERON:0004797	99.46	gold quality
ganglionic eminence	UBERON:0004023	99.08	gold quality
popliteal artery	UBERON:0002250	99.07	gold quality
tibial artery	UBERON:0007610	99.07	gold quality
embryo	UBERON:0000922	98.99	gold quality
artery	UBERON:0001637	98.96	gold quality
squamous epithelium	UBERON:0006914	98.92	gold quality
esophagus squamous epithelium	UBERON:0006920	98.91	gold quality
right coronary artery	UBERON:0001625	98.88	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.77	gold quality
parietal pleura	UBERON:0002400	98.70	gold quality
gingival epithelium	UBERON:0001949	98.60	gold quality
aorta	UBERON:0000947	98.54	gold quality
mucosa of stomach	UBERON:0001199	98.53	gold quality
gingiva	UBERON:0001828	98.50	gold quality
epithelium of esophagus	UBERON:0001976	98.50	gold quality
cranial nerve II	UBERON:0000941	98.49	gold quality
coronary artery	UBERON:0001621	98.40	gold quality
left coronary artery	UBERON:0001626	98.35	gold quality
descending thoracic aorta	UBERON:0002345	98.13	gold quality
thoracic aorta	UBERON:0001515	97.86	gold quality
pleura	UBERON:0000977	97.79	gold quality
ascending aorta	UBERON:0001496	97.79	gold quality
cervix epithelium	UBERON:0004801	97.78	gold quality
urethra	UBERON:0000057	97.50	gold quality
endothelial cell	CL:0000115	97.35	gold quality
renal medulla	UBERON:0000362	97.04	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.95	gold quality
esophagus mucosa	UBERON:0002469	96.92	gold quality
ventricular zone	UBERON:0003053	96.79	gold quality
esophagus	UBERON:0001043	96.71	gold quality
endocervix	UBERON:0000458	96.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.51	gold quality
visceral pleura	UBERON:0002401	96.50	gold quality
ectocervix	UBERON:0012249	96.50	gold quality
lower esophagus	UBERON:0013473	96.49	gold quality
uterine cervix	UBERON:0000002	96.47	gold quality
nephron tubule	UBERON:0001231	96.47	gold quality
gall bladder	UBERON:0002110	96.40	gold quality
mammalian vulva	UBERON:0000997	96.37	gold quality
vena cava	UBERON:0004087	96.35	gold quality
metanephros cortex	UBERON:0010533	96.29	gold quality
stromal cell of endometrium	CL:0002255	96.25	gold quality
right lung	UBERON:0002167	96.10	gold quality
choroid plexus epithelium	UBERON:0003911	96.09	gold quality
tibia	UBERON:0000979	95.98	gold quality
vagina	UBERON:0000996	95.70	gold quality
saphenous vein	UBERON:0007318	95.68	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.47	gold quality
mucosa of urinary bladder	UBERON:0001259	95.45	gold quality
adult mammalian kidney	UBERON:0000082	95.41	gold quality
pericardium	UBERON:0002407	95.39	gold quality
nasal cavity mucosa	UBERON:0001826	95.34	gold quality
penis	UBERON:0000989	95.24	gold quality
body of uterus	UBERON:0009853	95.24	gold quality
right lobe of thyroid gland	UBERON:0001119	95.21	gold quality
fundus of stomach	UBERON:0001160	95.11	gold quality
oral cavity	UBERON:0000167	95.00	gold quality
tongue squamous epithelium	UBERON:0006919	94.98	gold quality
adipose tissue	UBERON:0001013	94.94	gold quality
placenta	UBERON:0001987	94.94	gold quality
superficial temporal artery	UBERON:0001614	94.90	gold quality
palpebral conjunctiva	UBERON:0001812	94.78	gold quality
renal glomerulus	UBERON:0000074	94.77	gold quality
left lobe of thyroid gland	UBERON:0001120	94.69	gold quality
kidney epithelium	UBERON:0004819	94.64	gold quality
connective tissue	UBERON:0002384	94.60	gold quality
kidney	UBERON:0002113	94.58	gold quality
metanephric glomerulus	UBERON:0004736	94.45	gold quality
adult organism	UBERON:0007023	94.44	gold quality
eye	UBERON:0000970	94.39	gold quality
thyroid gland	UBERON:0002046	94.39	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.24	gold quality
metanephros	UBERON:0000081	94.21	gold quality
urinary bladder	UBERON:0001255	94.18	gold quality
cardia of stomach	UBERON:0001162	94.04	gold quality
omental fat pad	UBERON:0010414	94.03	gold quality
peritoneum	UBERON:0002358	94.02	gold quality
prostate gland	UBERON:0002367	93.94	gold quality
left uterine tube	UBERON:0001303	93.88	gold quality
fallopian tube	UBERON:0003889	93.74	gold quality
sperm	CL:0000019	93.72	gold quality
cortex of kidney	UBERON:0001225	93.52	gold quality
oviduct epithelium	UBERON:0004804	93.30	gold quality
vermiform appendix	UBERON:0001154	93.14	gold quality
male germ cell	CL:0000015	93.08	gold quality
pharyngeal mucosa	UBERON:0000355	93.05	gold quality
pigmented layer of retina	UBERON:0001782	93.04	gold quality
thoracic mammary gland	UBERON:0005200	92.97	gold quality
mammary gland	UBERON:0001911	92.93	gold quality
calcaneal tendon	UBERON:0003701	92.89	gold quality
uterus	UBERON:0000995	92.88	gold quality
upper leg skin	UBERON:0004262	92.70	gold quality
female reproductive system	UBERON:0000474	92.65	gold quality
right uterine tube	UBERON:0001302	92.63	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	1550.15
E-HCAD-5	yes	1426.55
E-GEOD-84465	yes	721.78
E-MTAB-9435	yes	680.11
E-MTAB-8205	yes	578.97
E-MTAB-10287	yes	66.82
E-MTAB-6701	yes	63.32
E-GEOD-137537	yes	33.32
E-HCAD-11	yes	28.18
E-MTAB-7316	yes	26.04
E-MTAB-8410	yes	25.82
E-CURD-46	yes	11.76
E-MTAB-9388	yes	10.91
E-MTAB-10290	no	370.11
E-MTAB-10137	no	8.15

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spinal cord	tissue	93.7
Esophagus	tissue	92.1	medium
Medulla oblongata	tissue	89.3
Hippocampal formation	tissue	83.1
Placenta	tissue	78.9	low
Periaqueductal gray	tissue	69.3
Substantia nigra	tissue	64.6
Vagina	tissue	64.1	medium
Midbrain	tissue	62.3
Pons	tissue	62.2
Retina	tissue	60.3
Gallbladder	tissue	57.7	high
Cerebral cortex	tissue	56.3	medium
Motor cortex	tissue	56.3
Kidney	tissue	52.9	high
Prefrontal cortex	tissue	52.8
Somatosensory cortex	tissue	48.5
Superior colliculi	tissue	47.2
Retrosplenial and cingulate cortex	tissue	47.0
Occipital cortex	tissue	46.4
Temporal cortex	tissue	46.1
Cervix	tissue	45.1	medium
Retrosplenial cortex	tissue	44.9
Hypothalamus	tissue	44.8
Urinary bladder	tissue	44.2	not detected
Insular cortex	tissue	43.8
Fallopian tube	tissue	43.7	not detected
Entorhinal cortex	tissue	43.2
Prostate	tissue	43.1	medium
Adipose tissue	tissue	42.5	not detected
Cerebellum	tissue	41.0	high
Thalamus	tissue	40.8
Septum	tissue	37.8
Endometrium 1	tissue	35.5	medium
Tonsil	tissue	35.1	high
Amygdala	tissue	35.0
Smooth muscle	tissue	34.7	not detected
Liver	tissue	34.0	not detected
Tongue	tissue	32.1
Basal ganglia	tissue	31.2	low
Thyroid gland	tissue	30.9	medium
Appendix	tissue	30.8	high
Putamen	tissue	29.2
Pituitary gland	tissue	28.5
Ventral forebrain	tissue	27.1
Lymph node	tissue	26.1	high
Epididymis	tissue	25.7	high
Olfactory bulb	tissue	25.6
Corpus callosum	tissue	25.1
Thymus	tissue	25.1
Ovary	tissue	24.4	not detected
Choroid plexus	tissue	22.0
Heart muscle	tissue	21.4	not detected
Lung	tissue	19.6	not detected
Testis	tissue	18.3	low
Spleen	tissue	18.1	high
Breast	tissue	17.5	medium
Nucleus accumbens	tissue	17.4
Duodenum	tissue	16.2	high
Colon	tissue	16.1	high

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (333.8), Ventral spinal cord (93.7), Dorsal spinal cord (91.4), Dorsal hippocampus (83.1), Ventral hippocampus (67.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CREB1, SMAD2, SMAD3, SP1, SRF

miRNA regulators (miRDB)

Targeting CSRP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

28 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-550B-2-5P	96.56	64.61	646
HSA-MIR-6858-3P	96.37	64.41	771

Functional genomics

gnomAD constraint: pLI 0.000409, LOEUF 1.01, missense Z 0.713 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000311083 — one region, missense o/e 0.90.

Literature-anchored findings (GeneRIF, showing 6)

• the effect of proteasome inhibition on IL-10 activation of the IL-10E1 pathway [Il-10E1] (PMID:12861049)
• CSRP2 promoted cell proliferation, cell-cycle progression, in vitro colony formation and cell migration ability. Abnormal CSRP2 expression was associated with resistance to chemotherapy; sensitivity was restored by down-regulating CSRP2 expression. (PMID:28415593)
• Study showed that CSRP2, an invadopodial actin bundling protein, is upregulated by hypoxia in various breast cancer cell lines, as well as in pre-clinical and clinical breast tumor specimens and functionally characterized two hypoxia responsive elements within the proximal promoter of CSRP2 gene which are targeted by hypoxia-inducible factor-1 (HIF-1) and required for promoter transactivation in response to hypoxia. (PMID:29976963)
• CSRP2 suppresses colorectal cancer progression via p130Cas/Rac1 axis-meditated ERK, PAK, and HIPPO signaling pathways. (PMID:33042270)
• Role of CRP2-MRTF interaction in functions of myofibroblasts. (PMID:37164693)
• Significance of the p38MAPK-CRP2 axis in myofibroblastic phenotypic transition. (PMID:37899269)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	csrp2	ENSDARG00000011961
mus_musculus	Csrp2	ENSMUSG00000020186
rattus_norvegicus	Csrp2	ENSRNOG00000003772
drosophila_melanogaster	Mlp84B	FBGN0014863
drosophila_melanogaster	Mlp60A	FBGN0259209
caenorhabditis_elegans		WBGENE00003375

Paralogs (2): CSRP3 (ENSG00000129170), CSRP1 (ENSG00000159176)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1202907) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal vascular wound healing	2
increased myocardial fiber size	1
abnormal vascular smooth muscle physiology	1
abnormal intercalated disk morphology	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	P67966	100.0%	Diamond
Coturnix japonica	P67967	100.0%	Diamond
Bos taurus	Q32LE9	100.0%	Diamond
Pongo abelii	Q5RCT4	99.5%	Diamond
Arabidopsis thaliana	O04193	85.0%	Diamond
Helianthus annuus	P29675	72.0%	Diamond
Dictyostelium discoideum	Q9BIW5	45.2%	Diamond
Schizosaccharomyces pombe 972h-	O14014	43.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ZDHHC17	protein-coding	23390
E2F7	protein-coding	144455

Protein

Protein identifiers

Cysteine and glycine-rich protein 2 — Q16527 (reviewed: Q16527)

Alternative names: Cysteine-rich protein 2, LIM domain only protein 5, Smooth muscle cell LIM protein

All UniProt accessions (4): Q16527, A0A024RBB5, F8VQR7, F8VW96

UniProt curated annotations — full annotation on UniProt →

Function. Drastically down-regulated in response to PDGF-BB or cell injury, that promote smooth muscle cell proliferation and dedifferentiation. Seems to play a role in the development of the embryonic vascular system.

Subunit / interactions. Interacts with KAT14. The LIM domain 1 is necessary and sufficient for this interaction. Interacts with GLRX3.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in the aorta, but not in heart and skeletal muscle.

RefSeq proteins (9): NP_001287894, NP_001312, NP_001400464, NP_001400466, NP_001400467, NP_001400468, NP_001400469, NP_001400470, NP_001400471 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain

Pfam: PF00412

UniProt features (10 total): modified residue 5, domain 2, chain 1, short sequence motif 1, cross-link 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16527-F1	71.07	0.00

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

Functional residue map

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

Post-translational modifications (6)

Type	Positions
N6-acetyllysine	112, 131, 137, 161
N6-succinyllysine	137
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	91

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 259 (showing top): MODULE_52, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_SARCOMERE_ORGANIZATION, MODULE_66, MODULE_118, WEI_MYCN_TARGETS_WITH_E_BOX, BROWNE_HCMV_INFECTION_48HR_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, MODULE_75, PAPASPYRIDONOS_UNSTABLE_ATEROSCLEROTIC_PLAQUE_DN, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, LE_EGR2_TARGETS_UP

GO Biological Process (3): cell differentiation (GO:0030154), sarcomere organization (GO:0045214), muscle tissue development (GO:0060537)

GO Molecular Function (4): structural constituent of muscle (GO:0008307), actinin binding (GO:0042805), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), focal adhesion (GO:0005925), Z disc (GO:0030018)

GO top-level categories

14 GO namespaces:

Category	Terms
cellular anatomical structure	2
cellular developmental process	1
myofibril assembly	1
actomyosin structure organization	1
tissue development	1
animal gross anatomical part developmental process	1
structural molecule activity	1
cytoskeletal protein binding	1
cation binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cell-substrate junction	1
I band	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
focal adhesion	CC	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 670 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSRP2	PIAS1	O75925	550
CSRP2	SPARC	P09486	529
CSRP2	LMO1	P25800	526
CSRP2	MED14	O60244	441
CSRP2	PRL	P01236	427
CSRP2	RNF168	Q8IYW5	427
CSRP2	PIAS4	Q8N2W9	419
CSRP2	TAGLN	Q01995	399
CSRP2	LMO2	P25791	393
CSRP2	RNF8	O76064	388
CSRP2	SEPTIN4	O43236	360
CSRP2	LMCD1	Q9NZU5	358
CSRP2	CBX5	P45973	355
CSRP2	MSX1	P28360	341
CSRP2	ZYX	Q15942	327

IntAct

Human interaction partners of CSRP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
ARC	physical association	0.560	3
COG6	physical association	0.560	3
TRIM23	physical association	0.560	3
TRIM27	physical association	0.560	3
STK4	physical association	0.370	1

BioGRID (92 interactions; top human partners by supporting records): CCNF (Affinity Capture-MS; 2 records), RFWD2 (Proximity Label-MS; 2 records), AAR2 (Affinity Capture-MS), ACE2 (Affinity Capture-MS), ACTG1 (Cross-Linking-MS (XL-MS)), AGO2 (Affinity Capture-RNA), AGPS (Co-fractionation), AIMP2 (Affinity Capture-MS), ARC (Two-hybrid), ARHGAP11B (Affinity Capture-MS), ATG16L1 (Proximity Label-MS), BAP1 (Affinity Capture-MS), BIRC3 (Affinity Capture-MS), BMI1 (Affinity Capture-MS), BSG (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for CSRP2: 25 ClinVar records (0 pathogenic / likely pathogenic); 7 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 645):

Position(s)	Effect	Δscore	Sites
12:76860283	donor_loss	1.0000	2
12:76860415	acceptor_gain	1.0000
12:76863174–76863175	donor_loss	1.0000	5
12:76860282–76860283	donor_loss	0.9900	3
12:76860417	acceptor_gain	0.9900
12:76863345–76863346	acceptor_loss	0.9900	6
12:76866147–76866148	donor_loss	0.9900	6
12:76878936–76878937	donor_loss	0.9900	5
12:76863972	donor_gain	0.9800
12:76866144–76866146	donor_loss	0.9800	3

AlphaMissense

788 missense substitutions predicted likely pathogenic (of 1,264 scored), across 166 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H140	8	0.998	0.999
H31	8	0.996	0.999
D45	8	0.982	0.998
D83	8	0.974	0.994
F35	8	0.968	0.998
F144	8	0.967	0.998
S46	8	0.966	0.999
H52	8	0.930	0.993
H19	8	0.877	0.972
C58	7	1.000	1.000
C40	7	0.999	1.000
C61	7	0.999	1.000
C119	7	0.999	1.000
C122	7	0.999	1.000
W139	7	0.999	1.000
C143	7	0.999	1.000
C146	7	0.999	1.000
C149	7	0.999	1.000
C167	7	0.999	1.000
C170	7	0.999	1.000

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Disease associations

OMIM: gene MIM:601871 | disease phenotypes:

GWAS associations

7 associations:

Study	Trait	p-value
GCST012301_14	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	2e-7
GCST012295_3	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	7e-7
GCST012298_4	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	9e-7
GCST003833_8	Adult asthma	2e-6
GCST012299_22	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	2e-6
GCST012292_6	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	3e-6
GCST012300_1	Schizophrenia, bipolar disorder or major depressive disorder	5e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295833 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	4
bisphenol A	affects expression, decreases expression, decreases methylation	3
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Temozolomide	decreases response to substance, increases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	2
Doxorubicin	affects expression, increases expression	2
Estradiol	affects expression, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, decreases expression	2
Aflatoxin B1	decreases expression	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
TL8-506	affects cotreatment, increases expression	1
tungsten carbide	affects cotreatment, increases expression	1
lead acetate	increases expression	1
sodium arsenate	increases abundance, increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chloride	decreases reaction, increases expression	1
2-amino-9H-pyrido(2,3-b)indole	decreases expression	1
cobaltous chloride	increases expression, decreases reaction	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
hydroquinone	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118574	Binding	Binding affinity to CSRP2 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — *Bioorg Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.