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 protein folding. Located in nucleoplasm. Part of U2-type precatalytic spliceosome and catalytic step 2 spliceosome.

Source: NCBI Gene 10283 — RefSeq curated summary.

At a glance

• Gene–disease (curated): metaphyseal chondrodysplasia-retinitis pigmentosa syndrome (Definitive, ClinGen)
• GWAS associations: 34
• Clinical variants (ClinVar): 436 total — 32 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 65
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• 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: 29 — 18 protein_coding, 6 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

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

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.

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

256 total, 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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TAL1

miRNA regulators (miRDB)

34 targeting CWC27, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

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

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)

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

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 (50 total): strand 11, compositionally biased region 8, helix 6, 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.

PDB	Method	Resolution (Å)
2HQ6	X-RAY DIFFRACTION	1.75
4R3E	X-RAY DIFFRACTION	2
7DVQ	ELECTRON MICROSCOPY	2.89
8I0R	ELECTRON MICROSCOPY	3
6YVH	X-RAY DIFFRACTION	3.19
6FF4	ELECTRON MICROSCOPY	3.4
6FF7	ELECTRON MICROSCOPY	4.5
5Z58	ELECTRON MICROSCOPY	4.9
5Z56	ELECTRON MICROSCOPY	5.1

Predicted structure (AlphaFold)

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

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): 2, 346

Glycosylation sites (2): 109, 201

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9918481	Dengue Virus-Host Interactions

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 (5): nucleoplasm (GO:0005654), U2-type precatalytic spliceosome (GO:0071005), catalytic step 2 spliceosome (GO:0071013), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
mRNA Splicing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
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
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

Protein interactions and networks

STRING

2856 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CWC27	RNF113A	O15541	864
CWC27	CWC22	Q9HCG8	818
CWC27	CWC25	Q9NXE8	759
CWC27	BUD13	Q9BRD0	745
CWC27	YJU2	Q9BW85	742
CWC27	CDC5L	Q99459	718
CWC27	SLU7	O95391	691
CWC27	SNRNP200	O75643	689
CWC27	DHX38	Q92620	686
CWC27	PRPF8	Q6P2Q9	616
CWC27	CWC15	Q9P013	614
CWC27	PRPF18	Q99633	569
CWC27	CRNKL1	Q9BZJ0	556
CWC27	DHX15	O43143	540
CWC27	EFTUD2	Q15029	540

IntAct

40 interactions, top by confidence:

A	B	Type	Score
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
IGSF6	CETN3	psi-mi:“MI:0914”(association)	0.530
E	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L5	SETD1A	psi-mi:“MI:0914”(association)	0.530
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
CWC27	FRA10AC1	psi-mi:“MI:0915”(physical association)	0.370
YWHAZ	WDR62	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
VTI1B	NBAS	psi-mi:“MI:0914”(association)	0.350
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.350
EPB41L5	AP3B1	psi-mi:“MI:0914”(association)	0.350
HMGA1	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
ESR2		psi-mi:“MI:0914”(association)	0.350
ARRDC3	ESYT2	psi-mi:“MI:0914”(association)	0.350
SYT2	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
PLCD3	AP3B1	psi-mi:“MI:0914”(association)	0.350
SF3B1	RBM10	psi-mi:“MI:0914”(association)	0.350
SF3B1	FAM83G	psi-mi:“MI:0914”(association)	0.350
KRAS	IGKV2D-29	psi-mi:“MI:0914”(association)	0.350
ARMC7	RNF113A	psi-mi:“MI:0915”(physical association)	0.320
LMNA	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
BUD13	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
DGCR8	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (88): CWC27 (Affinity Capture-MS), CWC27 (Affinity Capture-MS), CWC27 (Affinity Capture-MS), LSM2 (Co-fractionation), LSM6 (Co-fractionation), CWC27 (Biochemical Activity), CWC27 (Affinity Capture-MS), CWC27 (Affinity Capture-MS), CWC27 (Affinity Capture-MS), CWC27 (Affinity Capture-MS), CWC27 (Affinity Capture-MS), CWC27 (Affinity Capture-MS), CWC27 (Affinity Capture-MS), CWC27 (Affinity Capture-MS), CWC27 (Proximity Label-MS)

ESM2 similar proteins: B2RY56, F4ICK8, F4IDC2, O15042, O15541, O42964, O48713, O49413, P49756, Q04870, Q17QX9, Q3SWT4, Q3TKY6, Q3TQI7, Q4IJ11, Q4P7X6, Q4R713, Q4WSM6, Q5AAR0, Q5BEG5, Q5R4D6, Q5R7W3, Q5R7X2, Q5XIB2, Q5XJE5, Q5ZM19, Q641X2, Q67ER4, Q6BQ49, Q6CGB2, Q6CVL1, Q6FVX3, Q6NV83, Q6UX04, Q75EH2, Q7ZW86, Q803E1, Q870S2, Q8C1D8, Q8CH02

Diamond homologs: D4AY02, G5EEW6, O42941, O74942, O93826, P0C196, P0C1I4, P0C1I5, P0C1I6, P0C1J0, P0C1J1, P0C1J2, P0CP84, P0CP85, P0CP86, P0CP87, P0CP88, P0CP89, P0CP90, P0CP91, P0CP92, P0CP93, P23284, P23285, P24367, P24369, P34790, P52012, P52013, P52014, P52017, P73789, P80311, P87051, Q08E11, Q09637, Q09928, Q13356, Q17QX9, Q27774

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CWC27	up-regulates	Spliceosomal_snRNP_assembly

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA Splicing - Major Pathway	9	15.4×	1e-06
Processing of Capped Intron-Containing Pre-mRNA	5	12.8×	3e-03
Dengue Virus-Host Interactions	6	8.6×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	8	17.0×	7e-06
RNA splicing	6	12.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	17
Uncertain significance	178
Likely benign	158
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074824	NM_005869.4(CWC27):c.1033dup (p.Arg345fs)	Pathogenic
1076530	NM_005869.4(CWC27):c.1156del (p.Ala387fs)	Pathogenic
1172712	NM_005869.4(CWC27):c.1066_1070del (p.Ala356fs)	Pathogenic
1419612	NM_005869.4(CWC27):c.606del (p.Phe202fs)	Pathogenic
1432599	NM_005869.4(CWC27):c.225dup (p.Glu76fs)	Pathogenic
1435690	NM_005869.4(CWC27):c.1002del (p.Lys334_Val335insTer)	Pathogenic
1441533	NM_005869.4(CWC27):c.17_20del (p.Ile6fs)	Pathogenic
1446771	NM_005869.4(CWC27):c.994del (p.Gln332fs)	Pathogenic
1454227	NM_005869.4(CWC27):c.94G>T (p.Glu32Ter)	Pathogenic
1454480	NM_005869.4(CWC27):c.1101T>G (p.Tyr367Ter)	Pathogenic
1458608	NM_005869.4(CWC27):c.926C>G (p.Ser309Ter)	Pathogenic
1687405	NM_005869.4(CWC27):c.427C>T (p.Arg143Ter)	Pathogenic
2023736	NM_005869.4(CWC27):c.829G>T (p.Glu277Ter)	Pathogenic
2146929	NM_005869.4(CWC27):c.1120C>T (p.Gln374Ter)	Pathogenic
2425424	NC_000005.9:g.(?64064974)(64100233_?)del	Pathogenic
2425425	NC_000005.9:g.(?64064974)(64181393_?)del	Pathogenic
2425426	NC_000005.9:g.(?64077728)(64096174_?)del	Pathogenic
2425427	NC_000005.9:g.(?64096055)(64100233_?)del	Pathogenic
2576223	NM_005869.4(CWC27):c.669+1G>A	Pathogenic
2769599	NM_005869.4(CWC27):c.326del (p.Asn109fs)	Pathogenic
2816802	NM_005869.4(CWC27):c.120dup (p.Ile41fs)	Pathogenic
2864998	NM_005869.4(CWC27):c.922A>T (p.Lys308Ter)	Pathogenic
2971458	NM_005869.4(CWC27):c.355C>T (p.Arg119Ter)	Pathogenic
3720904	NM_005869.4(CWC27):c.676A>T (p.Lys226Ter)	Pathogenic
426071	NM_005869.4(CWC27):c.495G>A (p.Glu165=)	Pathogenic
426072	NM_005869.4(CWC27):c.943G>T (p.Glu315Ter)	Pathogenic
426073	NM_005869.4(CWC27):c.1002dup (p.Val335fs)	Pathogenic
426074	NM_005869.4(CWC27):c.617C>A (p.Ser206Ter)	Pathogenic
4689671	NM_005869.4(CWC27):c.1122_1125del (p.Ser375fs)	Pathogenic
4766260	NM_005869.4(CWC27):c.1117del (p.Gln373fs)	Pathogenic

SpliceAI

2317 predictions. Top by Δscore:

Variant	Effect	Δscore
5:64768499:CCTTA:C	donor_loss	1.0000
5:64768500:CTTAC:C	donor_loss	1.0000
5:64768501:TTAC:T	donor_loss	1.0000
5:64768502:TAC:T	donor_loss	1.0000
5:64768503:A:AC	donor_gain	1.0000
5:64768504:C:CA	donor_loss	1.0000
5:64768504:C:CC	donor_gain	1.0000
5:64769186:A:T	donor_gain	1.0000
5:64769187:AGGTG:A	donor_loss	1.0000
5:64774686:TACA:T	acceptor_loss	1.0000
5:64774688:CAGGT:C	acceptor_loss	1.0000
5:64774689:A:AG	acceptor_gain	1.0000
5:64774689:AGGT:A	acceptor_loss	1.0000
5:64774690:G:GA	acceptor_gain	1.0000
5:64774690:GGTT:G	acceptor_gain	1.0000
5:64774690:GGTTT:G	acceptor_gain	1.0000
5:64774783:GGAAG:G	donor_gain	1.0000
5:64774784:GAAGG:G	donor_gain	1.0000
5:64774786:AGGTA:A	donor_loss	1.0000
5:64774787:GGTA:G	donor_loss	1.0000
5:64774788:GTAT:G	donor_loss	1.0000
5:64774789:T:A	donor_loss	1.0000
5:64781917:TCA:T	acceptor_loss	1.0000
5:64781918:CAG:C	acceptor_loss	1.0000
5:64781919:A:AG	acceptor_gain	1.0000
5:64781920:G:GA	acceptor_gain	1.0000
5:64781920:GCTT:G	acceptor_gain	1.0000
5:64781920:GCTTA:G	acceptor_gain	1.0000
5:64782034:G:GG	donor_gain	1.0000
5:64783827:A:AG	acceptor_gain	1.0000

AlphaMissense

3160 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:64774733:T:A	W29R	1.000
5:64774733:T:C	W29R	1.000
5:64781978:G:A	G66E	1.000
5:64783855:T:C	L91S	1.000
5:64783879:T:A	V99D	1.000
5:64783882:C:A	A100D	1.000
5:64783975:G:A	G131E	1.000
5:64788965:T:A	L205H	1.000
5:64788965:T:C	L205P	1.000
5:64788970:T:C	F207L	1.000
5:64788971:T:C	F207S	1.000
5:64788971:T:G	F207C	1.000
5:64788972:T:A	F207L	1.000
5:64788972:T:G	F207L	1.000
5:64769183:G:A	G13R	0.999
5:64769183:G:C	G13R	0.999
5:64769183:G:T	G13W	0.999
5:64769184:G:A	G13E	0.999
5:64774713:G:A	G22E	0.999
5:64774725:T:A	I26K	0.999
5:64774731:T:C	L28S	0.999
5:64774734:G:C	W29S	0.999
5:64774735:G:C	W29C	0.999
5:64774735:G:T	W29C	0.999
5:64774759:C:G	C37W	0.999
5:64774765:T:A	N39K	0.999
5:64774765:T:G	N39K	0.999
5:64781942:T:C	F54S	0.999
5:64781944:C:G	H55D	0.999
5:64781949:A:C	R56S	0.999

dbSNP variants (sampled 300 via entrez): RS1000026321 (5:64951232 T>C), RS1000033352 (5:64999982 A>C,G), RS1000058079 (5:64953706 TC>T), RS1000075203 (5:64862597 A>C), RS1000077612 (5:64914485 G>A), RS1000119627 (5:64868763 G>C), RS1000121820 (5:64770438 A>G), RS1000126330 (5:64907235 T>C), RS1000136132 (5:65009633 A>G), RS1000143507 (5:64864197 G>A), RS1000176640 (5:64932646 A>G), RS1000184825 (5:64777372 G>A), RS1000196053 (5:64802577 A>G), RS1000201467 (5:64822427 G>T), RS1000212104 (5:64869050 A>G)

Disease associations

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

GenCC curated gene-disease

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

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
metaphyseal chondrodysplasia-retinitis pigmentosa syndrome	Definitive	AR

Mondo (4): inherited retinal dystrophy (MONDO:0019118), metaphyseal chondrodysplasia-retinitis pigmentosa syndrome (MONDO:0009598), optic atrophy (MONDO:0003608), retinitis pigmentosa (MONDO:0019200)

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

HPO phenotypes

65 total (30 of 65 shown, 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

GWAS associations

34 associations (top):

Study	Trait	p-value
GCST001762_502	Obesity-related traits	9.000000e-06
GCST003081_4	Glucocorticoid-induced osteonecrosis (age 10 years and older)	3.000000e-06
GCST003384_1	Bladder cancer	5.000000e-11
GCST006366_2	Central corneal thickness	2.000000e-10
GCST006463_10	Urinary albumin excretion (no hypertensive medication)	1.000000e-08
GCST006479_133	Diverticular disease	3.000000e-09
GCST006586_16	Urinary albumin excretion	2.000000e-10
GCST006628_42	Systolic blood pressure	5.000000e-10
GCST008790_21	Urinary albumin-to-creatinine ratio	1.000000e-09
GCST008794_60	Urinary albumin-to-creatinine ratio	6.000000e-10
GCST009414_1	Central corneal thickness	6.000000e-11
GCST009640_50	Urinary albumin-to-creatinine ratio	8.000000e-10
GCST010002_29	Refractive error	2.000000e-16
GCST010796_1087	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-39
GCST010796_351	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_352	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-16
GCST010796_353	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-25
GCST010796_354	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-33
GCST010796_355	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-38
GCST010796_357	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-37
GCST010796_358	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-33
GCST010796_359	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-31
GCST010796_360	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-30
GCST010796_361	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-32
GCST010796_362	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-34
GCST010796_363	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-36
GCST010796_364	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-36
GCST010796_365	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-35
GCST010796_366	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-14
GCST010796_367	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-14

EFO canonical traits (7, from GWAS)

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 (4)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
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

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

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	decreases expression, increases abundance, affects expression, increases reaction	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)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)