CWC27

Summary

CWC27 (CWC27 spliceosome associated cyclophilin, HGNC:10664) is a protein-coding gene on chromosome 5q12.3, encoding Spliceosome-associated protein CWC27 homolog (Q6UX04). As part of the spliceosome, plays a role in pre-mRNA splicing.

Predicted to enable peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of U2-type precatalytic spliceosome and catalytic step 2 spliceosome.

Source: NCBI Gene 10283 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): metaphyseal chondrodysplasia-retinitis pigmentosa syndrome (Definitive, ClinGen)
• GWAS associations: 34 (top 3% of genes corpus-wide)
• Clinical variants (ClinVar): 477 total — 28 pathogenic, 22 likely-pathogenic (top 7% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈6% of expected missense variation)
• GTEx eGene: eQTL in 15 tissues, sQTL in 41 (q < 0.05)
• Phenotypes (HPO): 65
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.18 (unconstrained)
• MANE Select transcript: NM_005869

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10664
Approved symbol	CWC27
Name	CWC27 spliceosome associated cyclophilin
Location	5q12.3
Locus type	gene with protein product
Status	Approved
Aliases	NY-CO-10, SDCCAG-10
Ensembl gene	ENSG00000153015
Ensembl biotype	protein_coding
OMIM	617170
Entrez	10283

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 19 protein_coding, 6 retained_intron, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

MANE Select: ENST00000381070

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 5: 1

ENST00000381070, ENST00000485990, ENST00000506168, ENST00000508024, ENST00000545000, ENST00000607786, ENST00000685023, ENST00000685147, ENST00000685234, ENST00000686041, ENST00000687101, ENST00000687188, ENST00000687314, ENST00000688107, ENST00000688318, ENST00000688564, ENST00000688896, ENST00000689534, ENST00000689574, ENST00000691921, ENST00000692005, ENST00000692572, ENST00000692660, ENST00000692763, ENST00000693121, ENST00000693303, ENST00000693571, ENST00000693640, ENST00000693660, ENST00001035813, ENST00001078276, ENST00001135135

RefSeq mRNA: 5 — MANE Select: NM_005869 NM_001297644, NM_001297645, NM_001318000, NM_001364478, NM_005869

CCDS: CCDS3982, CCDS75252, CCDS93718, CCDS93719, CCDS93720

Canonical transcript exons

ENST00000381070 — 14 exons

Exon	Start	End
ENSE00001008355	64800248	64800327
ENSE00001149201	64804229	64804386
ENSE00001487414	64768930	64769188
ENSE00001850478	65018159	65018750
ENSE00003468977	64788951	64789020
ENSE00003500695	64885443	64885546
ENSE00003522928	64774691	64774787
ENSE00003546185	64971703	64971812
ENSE00003550097	64801302	64801332
ENSE00003569576	64783836	64783979
ENSE00003572630	64785481	64785579
ENSE00003582136	64781921	64782033
ENSE00003662026	64977135	64977238
ENSE00003694653	64786524	64786627

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 98.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.8671 / max 932.9849, expressed in 1789 samples.

Highest expression (Bgee): tendon of biceps brachii, medial globus pallidus, globus pallidus, tendon, ganglionic eminence.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CWC27 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 41 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 56 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Muscularis	sqtl	7.6e-31	+0.84	5:64975734:A:C
Artery Tibial	sqtl	9.9e-31	+0.72	5:64976601:T:C
Cells Cultured fibroblasts	sqtl	1.4e-29	+0.65	5:64957013:G:A
Testis	eqtl	2.2e-29	+0.28	5:64880092:A:G
Esophagus Gastroesophageal Junction	sqtl	2.5e-25	+0.83	5:64944631:G:A
Nerve Tibial	sqtl	2.5e-24	+0.64	5:64977191:G:A
Artery Aorta	sqtl	3.6e-23	+0.74	5:64944631:G:A
Colon Sigmoid	sqtl	3.5e-20	+0.77	5:64963750:C:T
Brain Frontal Cortex BA9	sqtl	1.5e-19	+1.00	5:64944631:G:A
Adipose Visceral Omentum	sqtl	1.8e-17	+0.55	5:64982178:A:G
Testis	sqtl	1.3e-16	+0.57	5:64846088:G:A
Brain Putamen basal ganglia	sqtl	8.5e-16	+0.77	5:64976601:T:C
Colon Transverse	sqtl	2.0e-15	+0.58	5:64980066:C:T
Brain Nucleus accumbens basal ganglia	sqtl	4.6e-14	+0.84	5:64953073:A:G
Brain Cortex	sqtl	5.4e-14	+0.98	5:64976601:T:C
Thyroid	sqtl	1.6e-13	+0.45	5:64957013:G:A
Brain Hippocampus	sqtl	2.2e-13	+0.89	5:64976601:T:C
Brain Caudate basal ganglia	sqtl	1.5e-12	+0.75	5:64944631:G:A
Esophagus Mucosa	sqtl	6.1e-12	+0.42	5:64963750:C:T
Cells EBV-transformed lymphocytes	sqtl	7.5e-12	+0.75	5:64975734:A:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
56677	24.8542	1789
56679	0.6255	265
56680	0.3875	101

Top tissues by expression

showing 100 of 256 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.00	gold quality
medial globus pallidus	UBERON:0002477	95.91	gold quality
globus pallidus	UBERON:0001875	94.73	gold quality
tendon	UBERON:0000043	93.76	gold quality
ganglionic eminence	UBERON:0004023	93.74	gold quality
cortical plate	UBERON:0005343	93.04	gold quality
seminal vesicle	UBERON:0000998	93.01	gold quality
ventricular zone	UBERON:0003053	92.11	gold quality
postcentral gyrus	UBERON:0002581	91.75	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.74	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.66	gold quality
calcaneal tendon	UBERON:0003701	91.44	gold quality
lateral globus pallidus	UBERON:0002476	91.40	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.66	gold quality
parietal lobe	UBERON:0001872	90.60	gold quality
substantia nigra pars compacta	UBERON:0001965	90.54	gold quality
entorhinal cortex	UBERON:0002728	90.09	gold quality
islet of Langerhans	UBERON:0000006	89.69	gold quality
monocyte	CL:0000576	89.64	gold quality
left testis	UBERON:0004533	89.51	gold quality
leukocyte	CL:0000738	89.33	gold quality
testis	UBERON:0000473	89.21	gold quality
colonic epithelium	UBERON:0000397	89.13	gold quality
pylorus	UBERON:0001166	89.13	gold quality
right testis	UBERON:0004534	88.94	gold quality
primary visual cortex	UBERON:0002436	88.91	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.86	gold quality
superior frontal gyrus	UBERON:0002661	88.76	gold quality
corpus callosum	UBERON:0002336	88.66	gold quality
tibialis anterior	UBERON:0001385	88.61	silver quality
occipital lobe	UBERON:0002021	88.42	gold quality
putamen	UBERON:0001874	88.38	gold quality
pericardium	UBERON:0002407	88.32	gold quality
parietal pleura	UBERON:0002400	88.27	gold quality
deltoid	UBERON:0001476	88.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.05	gold quality
cardiac ventricle	UBERON:0002082	88.03	gold quality
heart left ventricle	UBERON:0002084	88.01	gold quality
nucleus accumbens	UBERON:0001882	87.94	gold quality
inferior vagus X ganglion	UBERON:0005363	87.86	gold quality
substantia nigra	UBERON:0002038	87.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.82	gold quality
Ammon’s horn	UBERON:0001954	87.81	gold quality
temporal lobe	UBERON:0001871	87.80	gold quality
caudate nucleus	UBERON:0001873	87.79	gold quality
hypothalamus	UBERON:0001898	87.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.57	gold quality
visceral pleura	UBERON:0002401	87.56	gold quality
medulla oblongata	UBERON:0001896	87.55	gold quality
gastrocnemius	UBERON:0001388	87.49	gold quality
amygdala	UBERON:0001876	87.49	gold quality
muscle of leg	UBERON:0001383	87.46	gold quality
midbrain	UBERON:0001891	87.44	gold quality
spinal cord	UBERON:0002240	87.39	gold quality
ventral tegmental area	UBERON:0002691	87.38	gold quality
heart right ventricle	UBERON:0002080	87.36	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.31	gold quality
cerebral cortex	UBERON:0000956	87.30	gold quality
renal medulla	UBERON:0000362	87.29	gold quality
heart	UBERON:0000948	87.26	gold quality
forebrain	UBERON:0001890	87.18	gold quality
biceps brachii	UBERON:0001507	87.15	gold quality
sural nerve	UBERON:0015488	87.12	gold quality
bone marrow cell	CL:0002092	87.09	gold quality
anterior cingulate cortex	UBERON:0009835	87.05	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.03	gold quality
right atrium auricular region	UBERON:0006631	86.91	gold quality
smooth muscle tissue	UBERON:0001135	86.85	gold quality
neocortex	UBERON:0001950	86.85	gold quality
apex of heart	UBERON:0002098	86.83	gold quality
brain	UBERON:0000955	86.80	gold quality
cardiac atrium	UBERON:0002081	86.73	gold quality
tibial artery	UBERON:0007610	86.72	gold quality
popliteal artery	UBERON:0002250	86.71	gold quality
superior vestibular nucleus	UBERON:0007227	86.61	gold quality
amniotic fluid	UBERON:0000173	86.57	gold quality
frontal cortex	UBERON:0001870	86.48	gold quality
mammary duct	UBERON:0001765	86.46	gold quality
quadriceps femoris	UBERON:0001377	86.45	gold quality
descending thoracic aorta	UBERON:0002345	86.43	gold quality
rectum	UBERON:0001052	86.41	gold quality
mucosa of transverse colon	UBERON:0004991	86.38	gold quality
epithelium of mammary gland	UBERON:0003244	86.37	gold quality
bone marrow	UBERON:0002371	86.36	gold quality
skeletal muscle tissue	UBERON:0001134	86.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.31	gold quality
aorta	UBERON:0000947	86.30	gold quality
vastus lateralis	UBERON:0001379	86.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.24	gold quality
lower esophagus	UBERON:0013473	86.23	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.19	gold quality
layer of synovial tissue	UBERON:0007616	86.11	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.09	gold quality
superficial temporal artery	UBERON:0001614	86.07	gold quality
esophagus squamous epithelium	UBERON:0006920	86.07	gold quality
prefrontal cortex	UBERON:0000451	85.99	gold quality
thymus	UBERON:0002370	85.96	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.92	gold quality
muscle tissue	UBERON:0002385	85.91	gold quality
right frontal lobe	UBERON:0002810	85.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.74
E-CURD-112	no	2.66

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Postcentral gyrus	tissue	44.2
Nucleus accumbens	tissue	39.5
Hippocampus	tissue	36.0	low
Choroid plexus	tissue	32.2
Locus coeruleus	tissue	31.2
Tongue	tissue	26.3
Skeletal muscle	tissue	23.0	medium
Bone marrow	tissue	22.4	high
Cerebellum	tissue	21.6	low
Thymus	tissue	21.2
Corpus callosum	tissue	20.4
Heart muscle	tissue	18.7	low
Ovary	tissue	18.7	medium
Olfactory bulb	tissue	18.3
Parathyroid gland	tissue	16.6	high
Putamen	tissue	16.6
Basal ganglia	tissue	16.5	low
Hippocampal formation	tissue	16.4
Septum	tissue	16.1
Periaqueductal gray	tissue	16.0
Ventral forebrain	tissue	15.9
Tonsil	tissue	15.6	medium
Spinal cord	tissue	15.5
Cerebral cortex	tissue	15.4	medium
Medulla oblongata	tissue	15.4
Retrosplenial and cingulate cortex	tissue	15.4
Lymph node	tissue	15.3	medium
Testis	tissue	15.2	high
Endometrium 1	tissue	15.2	medium
Temporal cortex	tissue	15.2
Occipital cortex	tissue	15.2
Retrosplenial cortex	tissue	15.1
Prefrontal cortex	tissue	15.0
Amygdala	tissue	15.0
Entorhinal cortex	tissue	15.0
Midbrain	tissue	14.8
Substantia nigra	tissue	14.8
Motor cortex	tissue	14.7
Insular cortex	tissue	14.7
Rectum	tissue	14.6	high
Hypothalamus	tissue	14.2
Placenta	tissue	14.2	high
Smooth muscle	tissue	14.1	medium
Somatosensory cortex	tissue	14.0
Thalamus	tissue	13.8
Thyroid gland	tissue	13.7	high
Kidney	tissue	13.7	high
Pons	tissue	13.5
Prostate	tissue	13.5	low
Superior colliculi	tissue	13.3
Adipose tissue	tissue	13.2	not detected
Breast	tissue	13.1	low
Urinary bladder	tissue	13.1	high
Appendix	tissue	13.0	medium
Adrenal gland	tissue	12.9	high
Colon	tissue	12.8	high
Spleen	tissue	12.7	not detected
Epididymis	tissue	12.4	low
Seminal vesicle	tissue	12.1	low
Esophagus	tissue	12.1	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Flocculonodular lobe (52.8), Vermis (51.9), Cerebellar cortex (51.5), Area striata (43.2), Parieto-temporal junction (white matter) (43.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TAL1

miRNA regulators (miRDB)

Targeting CWC27 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 34 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-3614-3P	97.81	67.15	582

Functional genomics

gnomAD constraint: pLI 4.16e-06, LOEUF 1.18, missense Z 0.755 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000381070 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈6% 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
5:64,769,147–65,018,169	463 / 498.1	0.93	no
5:65,018,170–65,018,255	12 / 34.1	0.35	yes (p 1.5e-04)
5:65,018,256–65,018,318	20 / 22.1	0.91	no

Literature-anchored findings (GeneRIF, showing 5)

• The crystal structure of a relatively protease-resistant N-terminal fragment of human Cwc27 containing the cyclophilin-type peptidyl-prolyl cis-trans isomerase domain was determined at 2.0 A resolution. (PMID:25478830)
• CWC27 overexpression is associated with Bladder Cancer. (PMID:27206850)
• By whole-exome sequencing, recessive protein-truncating mutations in CWC27 were found in seven unrelated families that show a range of clinical phenotypes, including retinal degeneration, brachydactyly, craniofacial abnormalities, short stature, and neurologic defects. (PMID:28285769)
• Structural and functional insights into CWC27/CWC22 heterodimer linking the exon junction complex to spliceosomes. (PMID:32329775)
• Further delineation of the CWC27-associated spliceosomeopathy: Case report and review of the literature. (PMID:36718996)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cwc27	ENSDARG00000043727
mus_musculus	Cwc27	ENSMUSG00000021715
rattus_norvegicus	Cwc27	ENSRNOG00000013252
drosophila_melanogaster	CG10907	FBGN0036207
caenorhabditis_elegans		WBGENE00000892

Paralogs (22): PPIE (ENSG00000084072), PPIL2 (ENSG00000100023), PPIF (ENSG00000108179), PPWD1 (ENSG00000113593), NKTR (ENSG00000114857), PPIL4 (ENSG00000131013), PPIL1 (ENSG00000137168), PPIG (ENSG00000138398), PPIB (ENSG00000166794), PPIC (ENSG00000168938), PPID (ENSG00000171497), PPIH (ENSG00000171960), PPIL6 (ENSG00000185250), PPIA (ENSG00000196262), PPIAL4G (ENSG00000236334), PPIL3 (ENSG00000240344), PPIAL4A (ENSG00000263353), PPIAL4H (ENSG00000270339), PPIAL4E (ENSG00000271567), PPIAL4F (ENSG00000279782), PPIAL4C (ENSG00000288867), PPIAL4D (ENSG00000289549)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914535) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, incomplete penetrance	2
postnatal growth retardation	1
abnormal immune system physiology	1
abnormal retina photoreceptor layer morphology	1
abnormal behavior	1
thin retina outer plexiform layer	1
abnormal blood homeostasis	1
prenatal growth retardation	1
decreased total retina thickness	1
decreased a-wave amplitude	1
decreased b-wave amplitude	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
Escherichia coli K-12	P0AFL3	100.0%	Diamond
Escherichia coli CFT073	P0AFL4	100.0%	Diamond
Escherichia coli O157:H7	P0AFL5	100.0%	Diamond
Cryptococcus deneoformans JEC21	P0CP84	100.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CP85	100.0%	Diamond
Mycobacterium tuberculosis variant bovis AF2122/97	P65763	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WHW2	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WHW3	100.0%	Diamond
Bos taurus	Q5E992	100.0%	Diamond
Pongo abelii	Q5NVL7	98.9%	Diamond
Macaca fascicularis	Q4R713	98.3%	Diamond
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2	P20753	95.8%	Diamond
Helicobacter pylori 26695	O25982	95.7%	Diamond
Helicobacter pylori J99	Q9ZJH5	95.7%	Diamond
Gallus gallus	Q5ZLV2	95.6%	Diamond
Aspergillus oryzae RIB40	Q2U6U0	93.8%	Diamond
Aspergillus nidulans FGSC A4	Q5ASQ0	93.8%	Diamond
Aspergillus fumigatus Af293	Q4WCR3	93.2%	Diamond
Aspergillus niger	Q8X191	93.0%	Diamond
Mycobacterium leprae TN	Q9CDE9	90.1%	Diamond
Fusarium graminearum PH-1	Q4I1Y1	80.4%	Diamond
Neurospora crassa OR74A	Q7SF72	79.4%	Diamond
Dickeya dadantii 3937	O53021	78.3%	Diamond
Schizosaccharomyces pombe 972h-	P87051	73.3%	Diamond
Rhizopus delemar RA 99-880	P0C1I5	73.1%	Diamond
Arabidopsis thaliana	Q9LPC7	73.0%	Diamond
Dictyostelium discoideum	Q54E95	71.1%	Diamond
Haemophilus influenzae Rd KW20	P44499	70.2%	Diamond
Mycosarcoma maydis	Q4PCH8	70.1%	Diamond
Xenopus laevis	Q6GLX7	67.2%	Diamond
Pseudomonas aeruginosa PAO1	Q59641	64.1%	Diamond
Acinetobacter baylyi ADP1	P42693	63.9%	Diamond
Streptococcus pyogenes MGAS10394	Q5XAQ1	63.8%	Diamond
Streptomyces anulatus	P77949	63.3%	Diamond
Synechococcus elongatus PCC 7942 = FACHB-805	P29820	63.1%	Diamond
Bacillus subtilis subsp. subtilis str. 168	P35137	59.6%	Diamond
Synechocystis sp. PCC 6803 substr. Kazusa	P72704	54.2%	Diamond
Yarrowia lipolytica CLIB122	Q6CGK4	44.2%	Diamond
Debaryomyces hansenii CBS767	Q6BWH6	41.8%	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
SREK1IP1	protein-coding	285672
ADAMTS6	protein-coding	11174
CENPK	protein-coding	64105
SHISAL2B	protein-coding	100132916

Protein

Protein identifiers

Spliceosome-associated protein CWC27 homolog — Q6UX04 (reviewed: Q6UX04)

Alternative names: Antigen NY-CO-10, Probable inactive peptidyl-prolyl cis-trans isomerase CWC27 homolog, Serologically defined colon cancer antigen 10

All UniProt accessions (19): Q6UX04, A0A8I5KP30, A0A8I5KP46, A0A8I5KPF6, A0A8I5KQK1, A0A8I5KQW2, A0A8I5KRF5, A0A8I5KRH9, A0A8I5KST0, A0A8I5KT14, A0A8I5KU89, A0A8I5KUR8, A0A8I5KUW8, A0A8I5KW10, A0A8I5KX65, A0A8I5KXM7, A0A8I5KY88, A0A8I5KZ67, D6REK3

UniProt curated annotations — full annotation on UniProt →

Function. As part of the spliceosome, plays a role in pre-mRNA splicing. Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.

Subunit / interactions. Part of the activated spliceosome B/catalytic step 1 spliceosome, one of the forms of the spliceosome which has a well-formed active site but still cannot catalyze the branching reaction and is composed at least of 52 proteins, the U2, U5 and U6 snRNAs and the pre-mRNA. Recruited during early steps of activated spliceosome B maturation, it is probably one of the first proteins released from this complex as he matures to the spliceosome C complex. Component of the minor spliceosome, which splices U12-type introns.

Subcellular location. Nucleus.

Disease relevance. Retinitis pigmentosa with or without skeletal anomalies (RPSKA) [MIM:250410] An autosomal recessive disease characterized by retinal degeneration, brachydactyly, short stature, craniofacial dysmorphism, and neurologic defects. Retinal defects are consistent with retinitis pigmentosa in most patients. Neurologic manifestations include mild-to-moderate intellectual disability and psychomotor retardation. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the cyclophilin-type PPIase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UX04-1	1	yes
Q6UX04-2	2

RefSeq proteins (5): NP_001284573, NP_001284574, NP_001304929, NP_001351407, NP_005860* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002130	Cyclophilin-type_PPIase_dom	Domain
IPR020892	Cyclophilin-type_PPIase_CS	Conserved_site
IPR029000	Cyclophilin-like_dom_sf	Homologous_superfamily
IPR044666	Cyclophilin_A-like	Family
IPR059998	CWC27_CTD	Domain

Pfam: PF00160

Enzyme classification (BRENDA)

• EC 5.2.1.8 — peptidylprolyl isomerase (BRENDA: 69 organisms, 374 substrates, 222 inhibitors, 24 Km, 30 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-SUCCINYL-ALA-GLU-(TRANS)-PRO-PHE-4-NITROANILID	0.17–0.7	5
N-SUCCINYL-ALA-ALA-(CIS)-PRO-PHE-4-NITROANILIDE	0.104–0.814	2
RNASE T1	0.0004–0.0006	2
SUCCINYL-ALA-ALA-PRO-PHE 4-NITROANILIDE	0.451–1.247	2
SUCCINYL-ALA-LYS-PRO-PHE-4-NITROANILIDE	0.585–0.788	2
ALA-GLY-PSI[CS-N]-PRO-PHE-4-NITROANILIDE	0.53	1
N-SUCCINYL-ALA-LEU-(CIS)-PRO-PHE-4-NITROANILIDE	0.059	1
SUCCINYL-ALA-GLU-PRO-PHE-7-AMIDO-4-METHYLCOUMARI	0.12	1
TRYWNAKMK-(CIS)-PFIFGA	2	1
SUCCINYL-ALA-ALA-(CIS)-PRO-LYS-4-METHYLCOUMARIN-	—	0
SUCCINYL-ALA-ALA-(CIS)-PRO-PHE 4-METHYLCOUMARIN	—	0

UniProt features (51 total): strand 11, compositionally biased region 8, helix 7, sequence variant 5, turn 5, modified residue 2, glycosylation site 2, splice variant 2, sequence conflict 2, region of interest 2, coiled-coil region 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

9 structures by resolution:

PDB	Title	Method	Resolution (Å)
2HQ6	Structure of the Cyclophilin_CeCYP16-Like Domain of the Serologically Defined Colon …	X-RAY DIFFRACTION	1.75
4R3E	Structure of the spliceosomal peptidyl-prolyl cis-trans isomerase Cwc27 from Homo sapiens	X-RAY DIFFRACTION	2
7DVQ	Cryo-EM Structure of the Activated Human Minor Spliceosome (minor Bact Complex)	ELECTRON MICROSCOPY	2.89
8I0R	The cryo-EM structure of human Bact-I complex	ELECTRON MICROSCOPY	3
6YVH	CWC22-CWC27-EIF4A3 Complex	X-RAY DIFFRACTION	3.19
6FF4	human Bact spliceosome core structure	ELECTRON MICROSCOPY	3.4
6FF7	human Bact spliceosome core structure	ELECTRON MICROSCOPY	4.5
5Z58	Cryo-EM structure of a human activated spliceosome (early Bact) at 4.9 angstrom.	ELECTRON MICROSCOPY	4.9
5Z56	cryo-EM structure of a human activated spliceosome (mature Bact) at 5.1 angstrom.	ELECTRON MICROSCOPY	5.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UX04-F1	73.93	0.27

Human Protein Atlas

Protein class: Metabolic proteins, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, Human disease related genes, Congenital malformations, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF enhanced

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 (2)

Type	Positions
N-acetylserine	2
Phosphoserine	346

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	109, 201

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 1 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-9918481	Dengue Virus-Host Interactions ⚕	curated
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: 301 (showing top): GOBP_PROTEIN_MATURATION, JAZAG_TGFB1_SIGNALING_DN, WANG_LMO4_TARGETS_DN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, KMCATNNWGGA_UNKNOWN, GOBP_RNA_SPLICING, GOBP_PROTEIN_FOLDING, REACTOME_MRNA_SPLICING, FISCHER_DREAM_TARGETS, chr5q12, ACEVEDO_LIVER_CANCER_UP, DANG_BOUND_BY_MYC, REACTOME_METABOLISM_OF_RNA, GOCC_U2_TYPE_SPLICEOSOMAL_COMPLEX, GOCC_PRECATALYTIC_SPLICEOSOME

GO Biological Process (3): mRNA splicing, via spliceosome (GO:0000398), protein folding (GO:0006457), protein peptidyl-prolyl isomerization (GO:0000413)

GO Molecular Function (2): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), isomerase activity (GO:0016853)

GO Cellular Component (4): nucleoplasm (GO:0005654), U2-type precatalytic spliceosome (GO:0071005), catalytic step 2 spliceosome (GO:0071013), nucleus (GO:0005634)

Reactome top-level categories

4 top-level categories:

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

GO top-level categories

20 GO namespaces:

Category	Terms
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
cellular process	1
protein maturation	1
peptidyl-proline modification	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
nuclear lumen	1
cellular anatomical structure	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1
catalytic complex	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
U2-type precatalytic spliceosome	CC	direct assay
catalytic step 2 spliceosome	CC	direct assay
nucleoplasm	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,350 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CWC27	RNF113A	O15541	752
CWC27	CWC25	Q9NXE8	737
CWC27	CWC22	Q9HCG8	693
CWC27	YJU2	Q9BW85	691
CWC27	SNRNP200	O75643	669
CWC27	SLU7	O95391	654
CWC27	DHX38	Q92620	634
CWC27	DHX16	O60231	580
CWC27	BUD13	Q9BRD0	532
CWC27	EFTUD2	Q15029	528
CWC27	PRPF3	O43395	520
CWC27	PRPF18	Q99633	517
CWC27	SF3B4	Q15427	486
CWC27	CDC5L	Q99459	476
CWC27	SF3A2	Q15428	473

IntAct

Human interaction partners of CWC27 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
FRA10AC1	physical association	0.370	1
E2F1	physical association	0.000	1

BioGRID (89 interactions; top human partners by supporting records): EDA (Affinity Capture-MS; 3 records), VTI1B (Affinity Capture-MS; 3 records), EPB41L5 (Affinity Capture-MS; 2 records), FRA10AC1 (Two-hybrid; 2 records), IGSF6 (Affinity Capture-MS; 2 records), LMNA (Proximity Label-MS; 2 records), AMBRA1 (Proximity Label-MS), ARRDC3 (Affinity Capture-MS), ASAP1 (Co-fractionation), ATG16L1 (Affinity Capture-MS), C9orf78 (Affinity Capture-MS), CAMKV (Affinity Capture-MS), CBX3 (Proximity Label-MS), CD3EAP (Proximity Label-MS), CHD8 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
CWC27	up-regulates	Spliceosomal_snRNP_assembly

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 CWC27: 477 ClinVar records (50 pathogenic / likely pathogenic); 34 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	22
Uncertain significance	189
Likely benign	178
Benign	17

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 50 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
426073	NM_005869.4(CWC27):c.1002dup (p.Val335fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
426071	NM_005869.4(CWC27):c.495G>A (p.Glu165=)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
850590	NM_005869.4(CWC27):c.1156dup (p.Leu386fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
987419	NM_005869.4(CWC27):c.666_669del (p.Ser222fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1172712	NM_005869.4(CWC27):c.1066_1070del (p.Ala356fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1068418	NM_005869.4(CWC27):c.938+2T>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	6
1068272	NM_005869.4(CWC27):c.1152+2T>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1693112	NM_005869.4(CWC27):c.397-1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3779554	NM_005869.4(CWC27):c.249_252+22del	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
843649	NM_005869.4(CWC27):c.77_78del (p.Ile26fs)	Pathogenic	criteria provided, single submitter	1
1074824	NM_005869.4(CWC27):c.1033dup (p.Arg345fs)	Pathogenic	criteria provided, single submitter	1
1076530	NM_005869.4(CWC27):c.1156del (p.Ala387fs)	Pathogenic	criteria provided, single submitter	1
1419612	NM_005869.4(CWC27):c.606del (p.Phe202fs)	Pathogenic	criteria provided, single submitter	1
1432599	NM_005869.4(CWC27):c.225dup (p.Glu76fs)	Pathogenic	criteria provided, single submitter	1
1441533	NM_005869.4(CWC27):c.17_20del (p.Ile6fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CWC27’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 1,006):

Position(s)	Effect	Δscore	Sites
5:64769186	donor_gain	1.0000
5:64769189–64769190	donor_loss	1.0000	5
5:64774689–64774690	acceptor_loss	1.0000	6
5:64774788–64774789	donor_loss	1.0000	5
5:64781919–64781920	acceptor_loss	1.0000	6
5:64783828–64783830	acceptor_gain	1.0000	2
5:64783835	acceptor_loss	1.0000	2
5:64783980	donor_loss	1.0000	2
5:64788943	acceptor_gain	1.0000
5:64789021	donor_loss	1.0000	2

AlphaMissense

1,433 missense substitutions predicted likely pathogenic (of 3,160 scored), across 312 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
F207	8	0.997	1.000
D67	8	0.993	0.997
H233	8	0.993	0.999
H88	8	0.992	0.999
D234	8	0.991	0.997
D448	8	0.991	0.999
F54	8	0.985	0.999
H55	8	0.984	0.999
S231	8	0.981	0.999
F392	8	0.981	0.999
F83	8	0.980	0.998
F113	8	0.980	0.999
F130	8	0.979	0.996
F114	8	0.978	0.998
D85	8	0.977	0.998
N39	8	0.976	0.999
D435	8	0.975	0.990
F40	8	0.973	0.998
S2	8	0.972	0.998
F93	8	0.969	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

6 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.5e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000169
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.00026
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	0.000417
Breast Invasive Carcinoma (validation)	unfavorable	0.000775
Lung Adenocarcinoma (TCGA)	unfavorable	0.000967

Disease associations

OMIM: gene MIM:617170 | disease phenotypes: MIM:250410, MIM:268000

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
metaphyseal chondrodysplasia-retinitis pigmentosa syndrome	Definitive	Autosomal recessive	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
metaphyseal chondrodysplasia-retinitis pigmentosa syndrome	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
DDG2P	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Retinal disorders	green

Mondo (3): metaphyseal chondrodysplasia-retinitis pigmentosa syndrome (MONDO:0009598), retinitis pigmentosa (MONDO:0019200), inherited retinal dystrophy (MONDO:0019118)

Orphanet (3): Brachydactyly-short stature-retinitis pigmentosa syndrome (Orphanet:166035), Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

showing 60 of 65 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000085	Horseshoe kidney
HP:0000107	Renal cyst
HP:0000256	Macrocephaly
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000430	Underdeveloped nasal alae
HP:0000494	Downslanted palpebral fissures
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000546	Retinal degeneration
HP:0000561	Absent eyelashes
HP:0000653	Sparse eyelashes
HP:0000662	Nyctalopia
HP:0000707	Abnormality of the nervous system
HP:0000750	Delayed speech and language development
HP:0000818	Abnormality of the endocrine system
HP:0000957	Cafe-au-lait spot
HP:0001123	Visual field defect
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001319	Neonatal hypotonia
HP:0001363	Craniosynostosis
HP:0001511	Intrauterine growth retardation
HP:0001596	Alopecia
HP:0001629	Ventricular septal defect
HP:0001763	Pes planus
HP:0001792	Small nail
HP:0001822	Hallux valgus
HP:0001999	Abnormal facial shape
HP:0002007	Frontal bossing
HP:0002120	Cerebral cortical atrophy
HP:0002194	Delayed gross motor development
HP:0002223	Absent eyebrow
HP:0002308	Chiari malformation
HP:0002342	Moderate intellectual disability
HP:0003577	Congenital onset
HP:0003621	Juvenile onset
HP:0004322	Short stature
HP:0005345	Abnormal vena cava morphology
HP:0005871	Metaphyseal chondrodysplasia
HP:0007099	Chiari type I malformation
HP:0007994	Peripheral visual field loss
HP:0008064	Ichthyosis
HP:0008070	Sparse hair
HP:0009882	Short distal phalanx of finger
HP:0009890	High anterior hairline
HP:0010049	Short metacarpal
HP:0010761	Broad columella
HP:0011463	Childhood onset
HP:0011968	Feeding difficulties
HP:0012471	Thick vermilion border
HP:0025159	Hypoautofluorescent retinal lesion
HP:0030148	Heart murmur
HP:0030455	Abnormality of pattern visual evoked potentials
HP:0030674	Antenatal onset

GWAS associations

showing 30 of 34 associations:

Study	Trait	p-value
GCST010796_743	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-40
GCST010796_1437	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-39
GCST010796_730	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-38
GCST010796_732	Electrocardiogram morphology (amplitude at temporal datapoints)	9e-37
GCST010796_739	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-36
GCST010796_738	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-36
GCST010796_740	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-35
GCST010796_737	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-34
GCST010796_733	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-33
GCST010796_729	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-33
GCST010796_736	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-32
GCST010796_734	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-31
GCST010796_735	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-30
GCST010796_728	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-25
GCST010002_104	Refractive error	2e-16
GCST010796_727	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-16
GCST010796_741	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-14
GCST010796_742	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-14
GCST003384_1	Bladder cancer	5e-11
GCST009414_19	Central corneal thickness	6e-11
GCST006366_3	Central corneal thickness	2e-10
GCST006586_9	Urinary albumin excretion	2e-10
GCST006628_42	Systolic blood pressure	5e-10
GCST008794_56	Urinary albumin-to-creatinine ratio	6e-10
GCST009640_34	Urinary albumin-to-creatinine ratio	8e-10
GCST008790_21	Urinary albumin-to-creatinine ratio	1e-9
GCST006479_4	Diverticular disease	3e-9
GCST011216_7	Left ventricular global radial strain	9e-9
GCST006463_18	Urinary albumin excretion (no hypertensive medication)	1e-8
GCST010988_445	Adult body size	1e-8

EFO canonical traits (from GWAS)

7 canonical traits:

EFO ID	Trait name
EFO:0005112	gestational age
EFO:0005213	central corneal thickness
EFO:0004285	albuminuria
EFO:0009959	diverticular disease
EFO:0006335	systolic blood pressure
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004327	electrocardiography

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C565398	Metaphyseal Chondrodysplasia with Retinitis Pigmentosa *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724776 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.15	Kd	71	nM	MOLIBRESIB
7.05	IC50	90	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179183: Binding affinity against SDCCAG10 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0710	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	5
sodium arsenite	increases abundance, increases expression	2
Cisplatin	decreases expression, affects cotreatment	2
Valproic Acid	decreases expression, increases expression	2
Particulate Matter	increases reaction, decreases expression, increases abundance, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
cylindrospermopsin	increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	affects expression, increases reaction	1
Daunorubicin	affects response to substance	1
Dexamethasone	affects cotreatment, increases expression	1
Dietary Carbohydrates	decreases expression	1
Estradiol	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Rotenone	decreases expression	1
T-2 Toxin	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697341	Binding	Inhibition of SDCCAG10 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — *Nature*

Clinical trials (associated diseases)

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

showing 60 of 271 trials:

NCT	Phase	Status	Title
NCT00717080	Phase 4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT04224207	Phase 3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	Phase 3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT00000114	Phase 3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	Phase 3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	Phase 3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	Phase 3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04636853	Phase 3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	Phase 3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	Phase 3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	Phase 3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	Phase 3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07290530	Phase 3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT07710196	Phase 3	NOT_YET_RECRUITING	A 24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT03763227	Phase 2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	Phase 2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	Phase 2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT00100230	Phase 2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	Phase 2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	Phase 2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	Phase 2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	Phase 2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	Phase 2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	Phase 2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	Phase 2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	Phase 2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	Phase 2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	Phase 2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	Phase 2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04356716	Phase 2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	Phase 2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	Phase 2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	Phase 2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT05085964	Phase 2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	Phase 2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	Phase 2	ACTIVE_NOT_RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	Phase 2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	Phase 2	ACTIVE_NOT_RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT07796646	Phase 2	NOT_YET_RECRUITING	Study to Evaluate the Long-Term Safety of Ultevursen in Participants With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT05902962	Phase 1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	Phase 1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	Phase 1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT01064505	Phase 1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	Phase 1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT00063765	Phase 1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	Phase 1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	Phase 1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa
NCT01068561	Phase 1	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT01482195	Phase 1	COMPLETED	Trial of Subretinal Injection of (rAAV2-VMD2-hMERTK)
NCT01531348	Phase 1	COMPLETED	Intravitreal Injection of MSCs in Retinitis Pigmentosa
NCT01543906	Phase 1	COMPLETED	Oral QLT091001 in Retinitis Pigmentosa (RP) Subjects With an Autosomal Dominant Mutation in Retinal Pigment Epithelial 65 Protein (RPE65)
NCT01604356	Phase 1	COMPLETED	Acupuncture for the Treatment of Vision Loss Due to Retinitis Pigmentosa
NCT01736059	Phase 1	ACTIVE_NOT_RECRUITING	Clinical Trial of Autologous Intravitreal Bone-marrow CD34+ Stem Cells for Retinopathy
NCT02280135	Phase 1	COMPLETED	Clinical Trial of Intravitreal Injection of Autologous Bone Marrow Stem Cells in Patients With Retinitis Pigmentosa
NCT03063021	Phase 1	COMPLETED	The FIGHT-RP1 Study
NCT03772938	Phase 1	UNKNOWN	Stem Cells Therapy in Degenerative Diseases of the Retina
NCT03944239	Phase 1	ACTIVE_NOT_RECRUITING	Safety and Efficacy of Subretinal Transplantation of Clinical Human Embryonic Stem Cell Derived Retinal Pigment Epitheliums in Treatment of Retinitis Pigmentosa
NCT03999021	Phase 1	ACTIVE_NOT_RECRUITING	FIGHT-RP 1 Extension Study
NCT04284293	Phase 1	ACTIVE_NOT_RECRUITING	CNS10-NPC for the Treatment of RP
NCT04925687	Phase 1	COMPLETED	Phase 1 Study of Intravitreal Autologous CD34+ Stem Cell Therapy for Retinitis Pigmentosa

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CWC27 across ~30M SureChEMBL compounds — explore on Sugi Predict.