CACTIN

Summary

CACTIN (cactin, spliceosome C complex subunit, HGNC:29938) is a protein-coding gene on chromosome 19p13.3, encoding Splicing factor Cactin (Q8WUQ7). Plays a role in pre-mRNA splicing by facilitating excision of a subset of introns. It is a common-essential gene (DepMap: required in 96.1% of cancer cell lines).

Enables RNA binding activity. Involved in several processes, including cellular response to cytokine stimulus; negative regulation of cytokine production; and negative regulation of signal transduction. Located in nuclear speck. Part of catalytic step 2 spliceosome.

Source: NCBI Gene 58509 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 109 total
• Regional missense constraint (gnomAD): 3 of 8 regions constrained (≈10% of expected missense variation)
• GTEx eGene: eQTL in 28 tissues, sQTL in 23 (q < 0.05)
• Cancer dependency (DepMap): dependent in 96.1% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.47 (moderately constrained)
• MANE Select transcript: NM_001080543
• Notable: 109 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29938
Approved symbol	CACTIN
Name	cactin, spliceosome C complex subunit
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	NY-REN-24, fSAPc
Ensembl gene	ENSG00000105298
Ensembl biotype	protein_coding
OMIM	618536
Entrez	58509

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 5 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000429344

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 3: 1, TSL 5: 4

ENST00000429344, ENST00000221899, ENST00000248420, ENST00000585942, ENST00000587175, ENST00000588749, ENST00000589321, ENST00000591726, ENST00000591978, ENST00000592721, ENST00000918263, ENST00001033287, ENST00001064585, ENST00001064586, ENST00001064587, ENST00001139143

RefSeq mRNA: 2 — MANE Select: NM_001080543 NM_001080543, NM_021231

CCDS: CCDS45920

Canonical transcript exons

ENST00000429344 — 10 exons

Exon	Start	End
ENSE00000664365	3620707	3620802
ENSE00001672817	3610645	3612413
ENSE00003591531	3613464	3613586
ENSE00003620216	3614397	3614589
ENSE00003634395	3613058	3613365
ENSE00003644846	3619080	3619242
ENSE00003645665	3620127	3620272
ENSE00003662668	3618875	3618989
ENSE00003739939	3623688	3624162
ENSE00003845105	3626596	3626790

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 89.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.2302 / max 133.8733, expressed in 1803 samples.

Highest expression (Bgee): sural nerve, granulocyte, ovary, hemisphere of cerebellum, olfactory bulb.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CACTIN is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 28 tissues and its splicing (sQTL) in 23 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 51 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	4.0e-39	-0.43	19:3613348:G:A
Testis	sqtl	3.1e-29	+0.92	19:3617908:A:C
Skin Not Sun Exposed Suprapubic	sqtl	2.5e-22	+0.62	19:3615409:G:A
Skin Sun Exposed Lower leg	sqtl	2.0e-21	+0.55	19:3617908:A:C
Thyroid	eqtl	1.2e-18	-0.21	19:3614852:G:T
Nerve Tibial	sqtl	2.8e-18	+0.55	19:3617421:C:G
Cells Cultured fibroblasts	eqtl	2.9e-14	-0.15	19:3613348:G:A
Adipose Subcutaneous	sqtl	6.6e-14	-0.50	19:3611974:G:A
Muscle Skeletal	eqtl	1.1e-12	-0.15	19:3627763:G:C
Thyroid	sqtl	4.4e-11	-0.47	19:3609723:A:G
Artery Aorta	eqtl	1.4e-10	-0.23	19:3615409:G:A
Nerve Tibial	eqtl	2.6e-10	-0.14	19:3627763:G:C
Adipose Subcutaneous	eqtl	2.2e-09	-0.15	19:3610454:T:C
Lung	eqtl	6.4e-09	-0.16	19:3614852:G:T
Whole Blood	eqtl	1.3e-08	-0.13	19:3651202:C:T
Artery Tibial	eqtl	1.6e-07	-0.13	19:3623231:A:T
Adipose Visceral Omentum	eqtl	1.1e-06	-0.16	19:3627763:G:C
Breast Mammary Tissue	sqtl	1.5e-06	-0.45	19:3615409:G:A
Colon Transverse	sqtl	1.8e-06	-0.53	19:3617908:A:C
Breast Mammary Tissue	eqtl	2.1e-06	-0.17	19:3614852:G:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
178324	12.8624	1801
178323	0.3678	162

Top tissues by expression

showing 100 of 286 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	89.80	gold quality
granulocyte	CL:0000094	89.01	gold quality
right ovary	UBERON:0002118	87.72	gold quality
left ovary	UBERON:0002119	87.71	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.62	gold quality
olfactory bulb	UBERON:0002264	86.44	silver quality
lower esophagus mucosa	UBERON:0035834	86.29	gold quality
type B pancreatic cell	CL:0000169	86.25	gold quality
left uterine tube	UBERON:0001303	85.94	gold quality
cerebellar hemisphere	UBERON:0002245	85.66	gold quality
cerebellar cortex	UBERON:0002129	85.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.58	gold quality
lower esophagus	UBERON:0013473	85.56	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.55	gold quality
apex of heart	UBERON:0002098	85.31	gold quality
body of uterus	UBERON:0009853	85.22	gold quality
gastrocnemius	UBERON:0001388	85.15	gold quality
mucosa of transverse colon	UBERON:0004991	85.05	gold quality
popliteal artery	UBERON:0002250	84.90	gold quality
tibial artery	UBERON:0007610	84.89	gold quality
left testis	UBERON:0004533	84.67	gold quality
right testis	UBERON:0004534	84.66	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.63	gold quality
stromal cell of endometrium	CL:0002255	84.60	gold quality
cerebellum	UBERON:0002037	84.60	gold quality
tibial nerve	UBERON:0001323	84.59	gold quality
skin of leg	UBERON:0001511	84.54	gold quality
aorta	UBERON:0000947	84.48	gold quality
body of stomach	UBERON:0001161	84.42	gold quality
muscle of leg	UBERON:0001383	84.36	gold quality
spleen	UBERON:0002106	84.34	gold quality
right frontal lobe	UBERON:0002810	84.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.33	gold quality
endocervix	UBERON:0000458	84.24	gold quality
prefrontal cortex	UBERON:0000451	84.22	gold quality
ascending aorta	UBERON:0001496	84.05	gold quality
mucosa of stomach	UBERON:0001199	84.02	gold quality
thoracic aorta	UBERON:0001515	84.02	gold quality
right lobe of liver	UBERON:0001114	83.97	gold quality
skin of abdomen	UBERON:0001416	83.95	gold quality
ganglionic eminence	UBERON:0004023	83.88	gold quality
right lobe of thyroid gland	UBERON:0001119	83.83	gold quality
ventricular zone	UBERON:0003053	83.82	gold quality
right coronary artery	UBERON:0001625	83.80	gold quality
metanephros cortex	UBERON:0010533	83.79	gold quality
oocyte	CL:0000023	83.73	gold quality
left coronary artery	UBERON:0001626	83.69	gold quality
descending thoracic aorta	UBERON:0002345	83.66	gold quality
tongue squamous epithelium	UBERON:0006919	83.61	silver quality
coronary artery	UBERON:0001621	83.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.41	gold quality
esophagus	UBERON:0001043	83.39	gold quality
ovary	UBERON:0000992	83.37	gold quality
transverse colon	UBERON:0001157	83.28	gold quality
amygdala	UBERON:0001876	83.28	gold quality
left lobe of thyroid gland	UBERON:0001120	83.26	gold quality
ectocervix	UBERON:0012249	83.24	gold quality
triceps brachii	UBERON:0001509	83.23	silver quality
muscle organ	UBERON:0001630	83.22	gold quality
left adrenal gland cortex	UBERON:0035825	83.15	gold quality
putamen	UBERON:0001874	83.11	gold quality
fundus of stomach	UBERON:0001160	83.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.04	gold quality
cortical plate	UBERON:0005343	83.03	gold quality
left adrenal gland	UBERON:0001234	82.96	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	82.92	silver quality
adenohypophysis	UBERON:0002196	82.68	gold quality
nucleus accumbens	UBERON:0001882	82.54	gold quality
right uterine tube	UBERON:0001302	82.52	gold quality
adrenal cortex	UBERON:0001235	82.45	gold quality
testis	UBERON:0000473	82.44	gold quality
thyroid gland	UBERON:0002046	82.42	gold quality
omental fat pad	UBERON:0010414	82.36	gold quality
heart left ventricle	UBERON:0002084	82.35	gold quality
peritoneum	UBERON:0002358	82.33	gold quality
vena cava	UBERON:0004087	82.28	silver quality
right adrenal gland	UBERON:0001233	82.27	gold quality
gluteal muscle	UBERON:0002000	82.27	silver quality
cingulate cortex	UBERON:0003027	82.27	gold quality
zone of skin	UBERON:0000014	82.22	gold quality
cardiac ventricle	UBERON:0002082	82.22	gold quality
stomach	UBERON:0000945	82.17	gold quality
caudate nucleus	UBERON:0001873	82.15	gold quality
esophagus mucosa	UBERON:0002469	82.15	gold quality
minor salivary gland	UBERON:0001830	82.09	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.09	gold quality
nasal cavity epithelium	UBERON:0005384	82.07	silver quality
secondary oocyte	CL:0000655	82.04	gold quality
anterior cingulate cortex	UBERON:0009835	82.03	gold quality
pituitary gland	UBERON:0000007	82.02	gold quality
frontal cortex	UBERON:0001870	81.97	gold quality
neocortex	UBERON:0001950	81.87	gold quality
small intestine	UBERON:0002108	81.86	gold quality
thymus	UBERON:0002370	81.83	silver quality
upper lobe of left lung	UBERON:0008952	81.83	gold quality
right atrium auricular region	UBERON:0006631	81.82	gold quality
CA1 field of hippocampus	UBERON:0003881	81.75	silver quality
cardiac atrium	UBERON:0002081	81.74	gold quality
body of pancreas	UBERON:0001150	81.72	gold quality
right adrenal gland cortex	UBERON:0035827	81.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.16

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Hippocampus	tissue	16.4	medium
Vagina	tissue	14.2	high
Nucleus accumbens	tissue	14.2
Frontal cortex	tissue	13.8
Postcentral gyrus	tissue	13.7
Caudate putamen	tissue	13.4
Pituitary gland	tissue	13.1
Skeletal muscle	tissue	13.1	high
Locus coeruleus	tissue	12.1
Spleen	tissue	10.0	medium
Bone marrow	tissue	9.4	high
Skin 1	tissue	9.1	medium
Choroid plexus	tissue	9.1
Thymus	tissue	8.1
Ovary	tissue	7.9	high
Cerebellum	tissue	7.6	medium
Corpus callosum	tissue	7.5
Appendix	tissue	7.4	high
Lymph node	tissue	7.1	high
Putamen	tissue	7.1
Cerebral cortex	tissue	7.0	medium
Hippocampal formation	tissue	7.0
Somatosensory cortex	tissue	7.0
Motor cortex	tissue	6.9
Superior colliculi	tissue	6.8
Ventral forebrain	tissue	6.7
Olfactory bulb	tissue	6.7
Prefrontal cortex	tissue	6.6
Adipose tissue	tissue	6.6	not detected
Basal ganglia	tissue	6.6	medium
Midbrain	tissue	6.6
Entorhinal cortex	tissue	6.6
Insular cortex	tissue	6.6
Substantia nigra	tissue	6.5
Small intestine	tissue	6.5	high
Spinal cord	tissue	6.4
Occipital cortex	tissue	6.4
Stomach 1	tissue	6.3	high
Salivary gland	tissue	6.3	medium
Medulla oblongata	tissue	6.3
Retrosplenial and cingulate cortex	tissue	6.3
Temporal cortex	tissue	6.3
Periaqueductal gray	tissue	6.2
Thalamus	tissue	6.1
Hypothalamus	tissue	6.1
Septum	tissue	6.1
Amygdala	tissue	6.0
Retrosplenial cortex	tissue	6.0
Pancreas	tissue	5.9	medium
Pons	tissue	5.8
Duodenum	tissue	5.8	high
Tongue	tissue	5.7
Adrenal gland	tissue	5.4	high
Testis	tissue	5.3	high
Endometrium 1	tissue	5.3	medium
Colon	tissue	4.8	high
Prostate	tissue	4.6	medium
Lung	tissue	4.5	high
Retina	tissue	4.3
Placenta	tissue	4.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Nucleus ambiguus (18.5), Orbitofrontal gyrus, anterior (17.5), Central amygdala (17.2), Lateral amygdala (17.2), Basal amygdala (17.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

showing 30 of 39 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-6849-3P	97.25	64.57	1371

Functional genomics

gnomAD constraint: pLI 0.997, LOEUF 0.465, missense Z 1.34 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000429344 splits into 8 regions with different missense tolerance; 3 are missense-constrained (≈10% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
19:3,611,926–3,612,046	21 / 61.8	0.34	yes (p 2.1e-07)
19:3,612,047–3,612,147	50 / 51.6	0.97	no
19:3,612,148–3,612,218	5 / 32.3	0.15	yes (p 1.6e-06)
19:3,612,219–3,612,255	0 / 16.5	0.00	yes (p 4.9e-05)
19:3,612,256–3,612,306	13 / 27.0	0.48	no
19:3,612,307–3,613,521	243 / 239.9	1.01	no
19:3,613,522–3,623,852	304 / 444.3	0.68	no
19:3,623,853–3,626,762	261 / 243.8	1.07	no
DepMap (CRISPR cell-line fitness): dependent in 96.1% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): S-117 (-2.323), NCI-H226 (-2.23), SNU-1077 (-2.049), NCI-H1092 (-1.93), KP-3 (-1.853), KP-2 (-1.815), MFE-280 (-1.813), SNU-216 (-1.774), TUHR10TKB (-1.75), MJ (-1.729), KLE (-1.701), HEL 92.1.7 (-1.697), Caki-2 (-1.65), NCI-H1915 (-1.623), TC-71 (-1.606).

Literature-anchored findings (GeneRIF, showing 3)

• results indicate that PKC-mediated cortactin phosphorylation might be implicated in the maintenance of growth cone (PMID:26033110)
• TRIM39 negatively regulates the NFkappaB signaling pathway possibly via stabilization of cactin. (PMID:26363554)
• cellular complexes comprising cactin, DHX8 and SRRM2 sustain precise chromosome segregation, genome stability and cell proliferation by allowing faithful splicing of specific pre-mRNAs. (PMID:28062851)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cactin	ENSDARG00000059866
mus_musculus	Cactin	ENSMUSG00000034889
rattus_norvegicus	Cactin	ENSRNOG00000039852
drosophila_melanogaster	cactin	FBGN0031114
caenorhabditis_elegans		WBGENE00012230

Paralogs (2): PQBP1 (ENSG00000102103), MARVELD3 (ENSG00000140832)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1917562) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal heart morphology	1
enlarged heart	1
abnormal spleen morphology	1
enlarged spleen	1
abnormal thymus morphology	1
enlarged thymus	1
abnormal testis morphology	1
small testis	1
abnormal seminal vesicle morphology	1
enlarged seminal vesicle	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	1
embryonic lethality prior to tooth bud stage	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
Toxoplasma gondii VEG	B6KG46	56.1%	Diamond
Arabidopsis thaliana	F4I2J8	36.7%	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
PIP5K1C	protein-coding	23396
TJP3	protein-coding	27134
CACTIN-AS1	ncRNA	404665
TBXA2R	protein-coding	6915
APBA3	protein-coding	9546
TEKTIP1	protein-coding	100128569
HMG20B	protein-coding	10362
MFSD12	protein-coding	126321
GIPC3	protein-coding	126326
MRPL54	protein-coding	116541

Protein

Protein identifiers

Splicing factor Cactin — Q8WUQ7 (reviewed: Q8WUQ7)

Alternative names: Renal carcinoma antigen NY-REN-24

All UniProt accessions (5): Q8WUQ7, K7EIU6, K7EMQ0, K7ENY9, K7EQE3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in pre-mRNA splicing by facilitating excision of a subset of introns. Required for the splicing of CDCA5/Sororin, a regulator of sister chromatid cohesion. Involved in the regulation of innate immune response. Acts as a negative regulator of Toll-like receptor, interferon-regulatory factor (IRF) and canonical NF-kappa-B signaling pathways. Contributes to the regulation of transcriptional activation of NF-kappa-B target genes in response to endogenous pro-inflammatory stimuli.

Subunit / interactions. Interacts (via N-terminal domain) with NFKBIL1; the interaction occurs in a pro-inflammatory-independent manner. Does not interact with RELA NF-kappa-B subunit. Identified in the spliceosome C complex. Interacts with SF3B1. Interacts with SDE2. Interacts with SRRM2. Interacts with DHX8. Interacts with isoform 2 of TRIM39 (via domain B box-type).

Subcellular location. Nucleus. Cytoplasm. Cytosol.

Induction. Up-regulated by TNF/TNFA (at protein level).

Miscellaneous. Antigen recognized by autologous antibody in patients with renal-cell carcinoma. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the CACTIN family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WUQ7-1	1	yes
Q8WUQ7-2	2

RefSeq proteins (2): NP_001074012, NP_067054 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018816	Cactin_central	Domain
IPR019134	Cactin_C	Domain

Pfam: PF09732, PF10312

UniProt features (35 total): strand 11, compositionally biased region 6, helix 4, region of interest 3, modified residue 3, cross-link 2, coiled-coil region 2, chain 1, splice variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

6 structures by resolution:

PDB	Title	Method	Resolution (Å)
8C6J	Human spliceosomal PM5 C* complex	ELECTRON MICROSCOPY	2.8
9XU3	Human minor spliceosome exon-ligation-ready C* complex (prior to step-II)	ELECTRON MICROSCOPY	3
6QDV	Human post-catalytic P complex spliceosome	ELECTRON MICROSCOPY	3.3
9FMD	Integrative model of the human post-catalytic spliceosome (P-complex)	ELECTRON MICROSCOPY	3.3
7W5A	The cryo-EM structure of human pre-C*-II complex	ELECTRON MICROSCOPY	3.6
7W5B	The cryo-EM structure of human C* complex	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUQ7-F1	69.52	0.13

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear speckles; nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF supported

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 (5)

Type	Positions
Phosphoserine	126, 476
Phosphotyrosine	559
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	469, 484

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-72163	mRNA Splicing - Major Pathway	curated
R-HSA-8953854	Metabolism of RNA	—
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA	—
R-HSA-72172	mRNA Splicing	—

MSigDB gene sets: 187 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (18): mRNA splicing, via spliceosome (GO:0000398), negative regulation of protein phosphorylation (GO:0001933), negative regulation of lipopolysaccharide-mediated signaling pathway (GO:0031665), negative regulation of interferon-beta production (GO:0032688), negative regulation of interleukin-8 production (GO:0032717), negative regulation of tumor necrosis factor production (GO:0032720), negative regulation of toll-like receptor signaling pathway (GO:0034122), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), innate immune response (GO:0045087), mRNA cis splicing, via spliceosome (GO:0045292), negative regulation of innate immune response (GO:0045824), negative regulation of type I interferon-mediated signaling pathway (GO:0060339), cellular response to lipopolysaccharide (GO:0071222), cellular response to interleukin-1 (GO:0071347), cellular response to tumor necrosis factor (GO:0071356), immune system process (GO:0002376), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear speck (GO:0016607), catalytic step 2 spliceosome (GO:0071013)

Reactome top-level categories

3 top-level categories:

Category	Pathways
mRNA Splicing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

showing 60 of 61 GO namespaces:

Category	Terms
cellular anatomical structure	3
negative regulation of response to biotic stimulus	2
negative regulation of signal transduction	2
negative regulation of response to external stimulus	2
cellular response to cytokine stimulus	2
RNA processing	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
regulation of protein phosphorylation	1
protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
lipopolysaccharide-mediated signaling pathway	1
regulation of lipopolysaccharide-mediated signaling pathway	1
negative regulation of type I interferon production	1
interferon-beta production	1
regulation of interferon-beta production	1
negative regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
toll-like receptor signaling pathway	1
negative regulation of immune system process	1
regulation of toll-like receptor signaling pathway	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
mRNA splicing, via spliceosome	1
negative regulation of defense response	1
innate immune response	1
regulation of innate immune response	1
negative regulation of immune response	1
negative regulation of cytokine-mediated signaling pathway	1
negative regulation of innate immune response	1
type I interferon-mediated signaling pathway	1
regulation of type I interferon-mediated signaling pathway	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
response to interleukin-1	1
response to tumor necrosis factor	1
biological_process	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to interleukin-1	BP	direct assay
cellular response to lipopolysaccharide	BP	direct assay
cellular response to tumor necrosis factor	BP	direct assay
mRNA splicing, via spliceosome	BP	mutant phenotype
negative regulation of canonical NF-kappaB signal transduction	BP	direct assay
negative regulation of interferon-beta production	BP	mutant phenotype
negative regulation of interleukin-8 production	BP	direct assay
negative regulation of lipopolysaccharide-mediated signaling pathway	BP	mutant phenotype
negative regulation of protein phosphorylation	BP	mutant phenotype
negative regulation of toll-like receptor signaling pathway	BP	direct assay
negative regulation of tumor necrosis factor production	BP	direct assay
negative regulation of type I interferon-mediated signaling pathway	BP	mutant phenotype
catalytic step 2 spliceosome	CC	direct assay
nuclear speck	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 16 of 1,070 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACTIN	FAM32A	Q9Y421	641
CACTIN	SDE2	Q6IQ49	619
CACTIN	PRKRIP1	Q9H875	511
CACTIN	CRNKL1	Q9BZJ0	509
CACTIN	TRIM39	Q9HCM9	508
CACTIN	TRIM9	Q9C026	436
CACTIN	INTS10	Q9NVR2	432
CACTIN	UTP20	O75691	431
CACTIN	WDR75	Q8IWA0	430
CACTIN	COMMD3	Q9UBI1	416
CACTIN	QTRT2	Q9H974	407
CACTIN	CWC25	Q9NXE8	400
CACTIN	OR1F1	O43749	385
CACTIN	TRIM11	Q96F44	376
CACTIN	SLU7	O95391	370
CACTIN	RNF216	Q9NWF9	370

IntAct

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

4 partners by confidence:

Partner	Interaction type	MIscore	Records
CLK2	physical association	0.560	3
SPTAN1	physical association	0.400	1
HMGB2	physical association	0.370	2
LST1	physical association	0.000	1

BioGRID (152 interactions; top human partners by supporting records): DHX8 (Affinity Capture-MS; 4 records), TRIM39 (Two-hybrid; 4 records), CXorf56 (Affinity Capture-MS; 3 records), C11orf57 (Affinity Capture-MS; 2 records), CHCHD10 (Affinity Capture-MS; 2 records), CLEC3A (Affinity Capture-MS; 2 records), CSNK2B (Affinity Capture-MS; 2 records), JMJD6 (Affinity Capture-MS; 2 records), JPH4 (Affinity Capture-MS; 2 records), LLGL2 (Affinity Capture-MS; 2 records), LMNA (Proximity Label-MS; 2 records), ACER3 (Affinity Capture-MS), ACTC1 (Proximity Label-MS), ANKRD50 (Affinity Capture-MS), APEX1 (Proximity Label-MS)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
C complex spliceosome	80	RBM8A, ZCCHC8, EFTUD2, HNRNPK, PNN, SRSF1, CDC40, DHX35, HNRNPA2B1, HNRNPC, SF3B3, SYNCRIP, U2AF1, PLRG1, RBM22, SNRNP40, SNRPB2, EIF4A3, FRG1, GPATCH1, HNRNPA3, PPIL1, SF3B1, DHX38, HNRNPR, LSM2, LSM3, SNRPE, DDX23, HNRNPU, MTREX, SLU7, AQR, CWC15, CWC22, DDX41, PABPC1, SF3B2, SNRPD1, SNRPD2, DHX8, CWC27, HNRNPA1, HNRNPH1, MAGOH, SF3A1, PPIE, PPIL3, PRP4K, PRPF6, RALY, SNRPA1, SYF2, TFIP11, CACTIN, CRNKL1, DDX5, SF3A3, SNRNP200, SNRPD3, SNRPF, SRRM1, ALYREF, PPWD1, PRPF19, RBMX, SF3A2, SRRM2, WDR83, XAB2, CDC5L, HNRNPF, SART1, SNRPG, ESS2, ISY1, SNRPB, SNW1, HNRNPM, PRPF8

Disease & clinical

Genetic variants

Variant evidence for CACTIN: 109 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	6
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 1,110):

Position(s)	Effect	Δscore	Sites
19:3614590	acceptor_loss	1.0000
19:3618873–3618874	donor_loss	1.0000	5
19:3618885	donor_gain	1.0000
19:3618990–3618991	acceptor_loss	1.0000	6
19:3619078–3619079	donor_loss	1.0000	4
19:3619243–3619244	acceptor_loss	1.0000	6
19:3619245	acceptor_gain	1.0000
19:3620131	donor_gain	1.0000
19:3620170	donor_gain	1.0000
19:3620803	acceptor_loss	1.0000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Bladder Urothelial Carcinoma (TCGA)	favorable	0.000302

Disease associations

OMIM: gene MIM:618536 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST001762_156	Obesity-related traits	6e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004626	IGFBP-3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	increases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Zoledronic Acid	decreases expression	1
Fulvestrant	increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Vehicle Emissions	decreases expression	1
Cisplatin	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Ribonucleotides	affects binding	1
Thiram	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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