# CWC22

> Gene · canonical: https://sugi.bio/atlas/gene/CWC22/
> Atlas v1.12.2 · generated 2026-10-13T13:32:47+00:00

## Summary

**CWC22** (CWC22 spliceosome associated protein, HGNC:29322) is a protein-coding gene on chromosome 2q31.3, encoding **Pre-mRNA-splicing factor CWC22 homolog** (Q9HCG8). Required for pre-mRNA splicing as component of the spliceosome. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nuclear speck. Part of U2-type catalytic step 1 spliceosome; U2-type catalytic step 2 spliceosome; and U2-type precatalytic spliceosome.

*Source: [NCBI Gene 57703](https://www.ncbi.nlm.nih.gov/gene/57703) — automated summary from GO annotations (Alliance of Genome Resources).*

**At a glance**

- **GWAS associations:** 6
- **Clinical variants (ClinVar):** 153 total
- **GTEx eGene:** eQTL in 23 tissues, sQTL in 2 (q < 0.05)
- **ChEMBL bioactivity:** 1 clinical-phase molecule tested; no curated mechanism-of-action drug
- **Cancer dependency (DepMap):** dependent in 99.7% of screened cell lines (common-essential)
- **Constraint (gnomAD):** pLI 0.00 (LoF-tolerant), LOEUF 0.88 (unconstrained)
- **MANE Select transcript:** `NM_020943`
- **Notable:** 153 clinical variants but no curated precision-oncology (CIViC) evidence yet




## Identifiers

### Gene identifiers

| Field | Value |
| --- | --- |
| HGNC ID | HGNC:29322 |
| Approved symbol | CWC22 |
| Name | CWC22 spliceosome associated protein |
| Location | 2q31.3 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | KIAA1604, EIF4GL, fSAPb, NCM |
| Ensembl gene | ENSG00000163510 |
| Ensembl biotype | protein_coding |
| OMIM | 615186 |
| Entrez | 57703 |

## Gene structure

### Transcript identifiers

**Ensembl transcripts: 18** — 12 protein_coding, 6 nonsense_mediated_decay

**MANE Select:** `ENST00000410053`

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

`ENST00000410053`, `ENST00000404136`, `ENST00000910802`, `ENST00000910803`, `ENST00000918074`, `ENST00000962033`, `ENST00000991800`, `ENST00000991802`, `ENST00000991803`, `ENST00001018788`, `ENST00001018789`, `ENST00001018790`, `ENST00001089234`, `ENST00001108107`, `ENST00001108108`, `ENST00001108109`, `ENST00001114122`, `ENST00001138810`

**RefSeq mRNA: 5** — MANE Select: `NM_020943`
`NM_001376029`, `NM_001376030`, `NM_001376032`, `NM_001376033`, `NM_020943`

**CCDS:** `CCDS46465`

#### Canonical transcript exons

`ENST00000410053` — 20 exons

| Exon | Start | End |
| --- | --- | --- |
| ENSE00001075491 | 179964547 | 179964628 |
| ENSE00001075494 | 179970501 | 179970563 |
| ENSE00001075498 | 179986695 | 179986805 |
| ENSE00001075504 | 179965878 | 179965982 |
| ENSE00001075505 | 179944876 | 179945715 |
| ENSE00001075506 | 179954957 | 179955034 |
| ENSE00001075507 | 179993315 | 179993454 |
| ENSE00001075509 | 179959022 | 179959082 |
| ENSE00001075511 | 179952471 | 179952598 |
| ENSE00001075514 | 179950512 | 179950732 |
| ENSE00001075517 | 179970941 | 179971076 |
| ENSE00001075520 | 179950825 | 179950926 |
| ENSE00001075522 | 179970650 | 179970856 |
| ENSE00001075525 | 179981752 | 179981997 |
| ENSE00001075529 | 179954205 | 179954357 |
| ENSE00001075532 | 179988577 | 179988644 |
| ENSE00001075534 | 179973193 | 179973246 |
| ENSE00001558768 | 180006867 | 180007297 |
| ENSE00001577932 | 179973634 | 179973802 |
| ENSE00001578434 | 179978190 | 179978318 |

### Expression profiles

**Bgee:** expression breadth **ubiquitous**, 251 present calls, max score 95.40.

**FANTOM5 (CAGE):** breadth **ubiquitous**, TPM avg 22.0498 / max 1277.4717, expressed in 1789 samples.

**Highest expression (Bgee):** epithelial cell of pancreas, calcaneal tendon, tendon, layer of synovial tissue, tendon of biceps brachii.

#### Genetic regulation across tissues (GTEx eQTL / sQTL)

CWC22 is an **eGene** in GTEx v10 — its expression is genetically regulated (eQTL) in **23** tissues and its splicing (sQTL) in **2** (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant's alternative allele.

showing 20 of 25 significant tissue × QTL associations:

| Tissue | QTL | q-value | Slope | Lead variant |
| --- | --- | --- | --- | --- |
| Whole Blood | eqtl | 5.5e-51 | +0.25 | 2:180004430:C:T |
| Thyroid | eqtl | 2.1e-13 | +0.37 | 2:179984363:A:T |
| Testis | eqtl | 2.3e-13 | +0.27 | 2:179984363:A:T |
| Pancreas | eqtl | 1.1e-12 | +0.57 | 2:179916817:C:T |
| Nerve Tibial | eqtl | 4.0e-08 | +0.27 | 2:179916817:C:T |
| Spleen | eqtl | 4.1e-07 | +0.41 | 2:179918444:G:A |
| Esophagus Mucosa | eqtl | 1.5e-06 | +0.22 | 2:179984363:A:T |
| Stomach | eqtl | 2.2e-06 | +0.34 | 2:179919676:A:G |
| Adipose Visceral Omentum | eqtl | 5.4e-06 | +0.23 | 2:180007524:A:T |
| Skin Not Sun Exposed Suprapubic | eqtl | 5.9e-05 | +0.20 | 2:179918444:G:A |
| Artery Tibial | eqtl | 6.8e-05 | +0.14 | 2:180007524:A:T |
| Colon Transverse | eqtl | 8.0e-05 | +0.70 | 2:179979343:C:T |
| Prostate | eqtl | 2.2e-04 | +0.33 | 2:179984363:A:T |
| Skin Sun Exposed Lower leg | eqtl | 3.3e-04 | +0.17 | 2:179984363:A:T |
| Esophagus Muscularis | eqtl | 7.7e-04 | +0.20 | 2:180007524:A:T |
| Pituitary | eqtl | 8.4e-04 | +0.37 | 2:179984363:A:T |
| Brain Cerebellar Hemisphere | eqtl | 2.6e-03 | +0.32 | 2:179984363:A:T |
| Adrenal Gland | eqtl | 4.2e-03 | +0.36 | 2:179918444:G:A |
| Brain Hypothalamus | eqtl | 9.2e-03 | -0.33 | 2:179510847:C:T |
| Brain Hippocampus | eqtl | 1.0e-02 | +0.36 | 2:179918444:G:A |

#### FANTOM5 promoters

2 alternative TSS:

| Promoter ID | TPM avg | Samples expressed |
| --- | --- | --- |
| 32708 | 19.7068 | 1780 |
| 32709 | 2.3430 | 1113 |

#### Top tissues by expression

showing 100 of 252 tissues by Bgee expression score (0-100, higher = more expressed):

| Tissue | Anatomy ID | Expression score | Quality |
| --- | --- | --- | --- |
| epithelial cell of pancreas | CL:0000083 | 95.40 | gold quality |
| calcaneal tendon | UBERON:0003701 | 92.78 | gold quality |
| tendon | UBERON:0000043 | 91.80 | gold quality |
| layer of synovial tissue | UBERON:0007616 | 91.49 | gold quality |
| tendon of biceps brachii | UBERON:0008188 | 89.87 | gold quality |
| amniotic fluid | UBERON:0000173 | 88.28 | gold quality |
| synovial joint | UBERON:0002217 | 88.17 | gold quality |
| epithelium of nasopharynx | UBERON:0001951 | 87.99 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 87.96 | gold quality |
| ventricular zone | UBERON:0003053 | 87.86 | gold quality |
| superficial temporal artery | UBERON:0001614 | 87.79 | gold quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 87.19 | gold quality |
| parietal pleura | UBERON:0002400 | 86.72 | gold quality |
| oral cavity | UBERON:0000167 | 86.70 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 86.29 | gold quality |
| endometrium | UBERON:0001295 | 86.21 | gold quality |
| visceral pleura | UBERON:0002401 | 86.10 | gold quality |
| biceps brachii | UBERON:0001507 | 86.02 | gold quality |
| islet of Langerhans | UBERON:0000006 | 85.85 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 85.57 | gold quality |
| leukocyte | CL:0000738 | 85.57 | gold quality |
| monocyte | CL:0000576 | 85.55 | gold quality |
| kidney epithelium | UBERON:0004819 | 85.55 | silver quality |
| lymph node | UBERON:0000029 | 85.39 | gold quality |
| gingival epithelium | UBERON:0001949 | 85.39 | gold quality |
| seminal vesicle | UBERON:0000998 | 85.35 | gold quality |
| upper arm skin | UBERON:0004263 | 85.24 | silver quality |
| gingiva | UBERON:0001828 | 85.20 | gold quality |
| popliteal artery | UBERON:0002250 | 85.16 | gold quality |
| tibial artery | UBERON:0007610 | 85.15 | gold quality |
| deltoid | UBERON:0001476 | 84.75 | gold quality |
| ganglionic eminence | UBERON:0004023 | 84.70 | gold quality |
| mucosa of paranasal sinus | UBERON:0005030 | 84.69 | gold quality |
| secondary oocyte | CL:0000655 | 84.66 | gold quality |
| sural nerve | UBERON:0015488 | 84.65 | gold quality |
| upper leg skin | UBERON:0004262 | 84.63 | gold quality |
| placenta | UBERON:0001987 | 84.56 | gold quality |
| uterus | UBERON:0000995 | 84.48 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 84.29 | gold quality |
| aorta | UBERON:0000947 | 84.23 | gold quality |
| gastrocnemius | UBERON:0001388 | 84.17 | gold quality |
| skin of hip | UBERON:0001554 | 84.11 | gold quality |
| left ovary | UBERON:0002119 | 83.94 | gold quality |
| cortical plate | UBERON:0005343 | 83.93 | gold quality |
| vermiform appendix | UBERON:0001154 | 83.91 | gold quality |
| rectum | UBERON:0001052 | 83.90 | gold quality |
| ovary | UBERON:0000992 | 83.89 | gold quality |
| tonsil | UBERON:0002372 | 83.89 | gold quality |
| female reproductive system | UBERON:0000474 | 83.70 | gold quality |
| gall bladder | UBERON:0002110 | 83.69 | gold quality |
| urinary bladder | UBERON:0001255 | 83.66 | gold quality |
| muscle of leg | UBERON:0001383 | 83.66 | gold quality |
| tibia | UBERON:0000979 | 83.61 | gold quality |
| body of uterus | UBERON:0009853 | 83.54 | gold quality |
| myocardium | UBERON:0002349 | 83.47 | silver quality |
| mucosa of sigmoid colon | UBERON:0004993 | 83.35 | gold quality |
| endocervix | UBERON:0000458 | 83.34 | gold quality |
| thymus | UBERON:0002370 | 83.30 | gold quality |
| right ovary | UBERON:0002118 | 83.26 | gold quality |
| muscle tissue | UBERON:0002385 | 83.24 | gold quality |
| subcutaneous adipose tissue | UBERON:0002190 | 83.18 | gold quality |
| left uterine tube | UBERON:0001303 | 83.05 | gold quality |
| thoracic aorta | UBERON:0001515 | 83.04 | gold quality |
| skeletal muscle tissue | UBERON:0001134 | 82.98 | gold quality |
| pigmented layer of retina | UBERON:0001782 | 82.98 | gold quality |
| adrenal tissue | UBERON:0018303 | 82.92 | gold quality |
| ascending aorta | UBERON:0001496 | 82.91 | gold quality |
| parotid gland | UBERON:0001831 | 82.88 | gold quality |
| pericardium | UBERON:0002407 | 82.88 | gold quality |
| colonic mucosa | UBERON:0000317 | 82.87 | gold quality |
| jejunum | UBERON:0002115 | 82.85 | gold quality |
| left coronary artery | UBERON:0001626 | 82.83 | gold quality |
| adipose tissue | UBERON:0001013 | 82.76 | gold quality |
| ectocervix | UBERON:0012249 | 82.72 | gold quality |
| coronary artery | UBERON:0001621 | 82.66 | gold quality |
| myometrium | UBERON:0001296 | 82.64 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 82.61 | gold quality |
| mucosa of stomach | UBERON:0001199 | 82.58 | gold quality |
| palpebral conjunctiva | UBERON:0001812 | 82.57 | gold quality |
| peritoneum | UBERON:0002358 | 82.55 | gold quality |
| omental fat pad | UBERON:0010414 | 82.55 | gold quality |
| tibialis anterior | UBERON:0001385 | 82.54 | silver quality |
| fallopian tube | UBERON:0003889 | 82.50 | gold quality |
| quadriceps femoris | UBERON:0001377 | 82.48 | silver quality |
| ileal mucosa | UBERON:0000331 | 82.47 | gold quality |
| caecum | UBERON:0001153 | 82.45 | gold quality |
| bone marrow | UBERON:0002371 | 82.41 | gold quality |
| right coronary artery | UBERON:0001625 | 82.34 | gold quality |
| uterine cervix | UBERON:0000002 | 82.31 | gold quality |
| esophagogastric junction muscularis propria | UBERON:0035841 | 82.28 | gold quality |
| pancreatic ductal cell | CL:0002079 | 82.23 | silver quality |
| adipose tissue of abdominal region | UBERON:0007808 | 82.19 | gold quality |
| lower esophagus | UBERON:0013473 | 82.16 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 82.16 | gold quality |
| vastus lateralis | UBERON:0001379 | 82.14 | silver quality |
| cauda epididymis | UBERON:0004360 | 82.14 | gold quality |
| jejunal mucosa | UBERON:0000399 | 82.10 | gold quality |
| pancreas | UBERON:0001264 | 82.08 | gold quality |
| vagina | UBERON:0000996 | 81.99 | gold quality |
| cartilage tissue | UBERON:0002418 | 81.99 | gold quality |

#### Single-cell (SCXA)

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

| Experiment | Marker? | Max mean expression |
| --- | --- | --- |
| [E-MTAB-7303](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-7303) | no | 68.52 |
| [E-ANND-3](https://www.ebi.ac.uk/gxa/sc/experiments/E-ANND-3) | no | 0.00 |

#### HPA expression

RNA tissue specificity: **Low tissue specificity**

showing 60 of 79 HPA tissues / cells by nTPM:

| Tissue / cell | Axis | nTPM | Protein (IHC) |
| --- | --- | --- | --- |
| Cerebellum | tissue | 29.3 | high |
| Thymus | tissue | 20.3 |  |
| Olfactory bulb | tissue | 19.3 |  |
| Hippocampal formation | tissue | 18.5 |  |
| Putamen | tissue | 18.4 |  |
| Cerebral cortex | tissue | 18.2 | high |
| Midbrain | tissue | 18.2 |  |
| Occipital cortex | tissue | 18.2 |  |
| Spinal cord | tissue | 17.9 |  |
| Corpus callosum | tissue | 17.9 |  |
| Superior colliculi | tissue | 17.8 |  |
| Postcentral gyrus | tissue | 17.8 |  |
| Septum | tissue | 17.7 |  |
| Pons | tissue | 17.6 |  |
| Somatosensory cortex | tissue | 17.6 |  |
| Lymph node | tissue | 17.3 | medium |
| Nucleus accumbens | tissue | 17.1 |  |
| Medulla oblongata | tissue | 17.1 |  |
| Thalamus | tissue | 17.0 |  |
| Tonsil | tissue | 17.0 | high |
| Retrosplenial and cingulate cortex | tissue | 16.8 |  |
| Prefrontal cortex | tissue | 16.6 |  |
| Substantia nigra | tissue | 16.6 |  |
| Ventral forebrain | tissue | 16.6 |  |
| Retrosplenial cortex | tissue | 16.5 |  |
| Entorhinal cortex | tissue | 16.4 |  |
| Motor cortex | tissue | 16.3 |  |
| Periaqueductal gray | tissue | 16.3 |  |
| Choroid plexus | tissue | 16.2 |  |
| Hypothalamus | tissue | 16.1 |  |
| Basal ganglia | tissue | 16.0 | high |
| Endometrium 1 | tissue | 15.8 | high |
| Hippocampus | tissue | 15.8 | high |
| Temporal cortex | tissue | 15.8 |  |
| Liver | tissue | 15.7 | high |
| Ovary | tissue | 15.6 | medium |
| Amygdala | tissue | 15.2 |  |
| Bone marrow | tissue | 15.1 | high |
| Thyroid gland | tissue | 15.0 | high |
| Insular cortex | tissue | 14.4 |  |
| Breast | tissue | 14.0 | high |
| Spleen | tissue | 13.9 | medium |
| Tongue | tissue | 13.6 |  |
| Placenta | tissue | 13.6 | high |
| Cervix | tissue | 13.2 | high |
| Urinary bladder | tissue | 13.1 | high |
| Smooth muscle | tissue | 13.0 | high |
| Locus coeruleus | tissue | 12.8 |  |
| Parathyroid gland | tissue | 12.7 | medium |
| Kidney | tissue | 12.5 | high |
| Appendix | tissue | 12.4 | high |
| Caudate putamen | tissue | 12.2 |  |
| Adipose tissue | tissue | 11.9 | medium |
| Esophagus | tissue | 11.7 | high |
| Prostate | tissue | 11.7 | high |
| Retina | tissue | 11.5 |  |
| Gallbladder | tissue | 11.3 | high |
| Fallopian tube | tissue | 11.3 | high |
| Rectum | tissue | 11.1 | high |
| Vagina | tissue | 10.9 | high |

**Brain sub-regions (HPA Brain Atlas):** detected in 192; highest nTPM — Cerebellar cortex (29.4), Flocculonodular lobe (27.0), Vermis (26.8), Angular gyrus (white matter) (19.4), Corpus callosum, genu (white matter) (19.3).

### Regulation

**Is transcription factor: no**

#### miRNA regulators (miRDB)

Targeting CWC22 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 48 miRNAs:

| miRNA | Max score | Avg score | miRNA target_count |
| --- | --- | --- | --- |
| HSA-MIR-340-5P | 100.00 | 72.50 | 4437 |
| HSA-MIR-3163 | 100.00 | 77.23 | 8605 |
| HSA-LET-7A-3P | 100.00 | 74.03 | 3932 |
| HSA-LET-7B-3P | 100.00 | 74.08 | 3913 |
| HSA-LET-7F-1-3P | 100.00 | 74.02 | 3928 |
| HSA-MIR-98-3P | 100.00 | 74.08 | 3907 |
| HSA-MIR-3646 | 100.00 | 73.56 | 5283 |
| HSA-MIR-5692A | 100.00 | 74.40 | 6850 |
| HSA-MIR-513B-5P | 99.99 | 69.96 | 2150 |
| HSA-MIR-3662 | 99.99 | 73.82 | 5684 |
| HSA-MIR-4775 | 99.98 | 75.00 | 6394 |
| HSA-LET-7F-2-3P | 99.98 | 70.98 | 2588 |
| HSA-MIR-1185-1-3P | 99.98 | 71.04 | 2593 |
| HSA-MIR-1185-2-3P | 99.98 | 71.04 | 2593 |
| HSA-MIR-4789-5P | 99.98 | 70.76 | 2721 |
| HSA-MIR-520D-5P | 99.98 | 73.34 | 4883 |
| HSA-MIR-524-5P | 99.98 | 73.43 | 4882 |
| HSA-MIR-607 | 99.97 | 73.62 | 5593 |
| HSA-MIR-570-3P | 99.96 | 72.41 | 4910 |
| HSA-MIR-4666A-3P | 99.96 | 71.71 | 3434 |
| HSA-MIR-548AT-5P | 99.96 | 70.83 | 2666 |
| HSA-MIR-590-3P | 99.96 | 74.34 | 6478 |
| HSA-MIR-1250-3P | 99.96 | 70.04 | 4038 |
| HSA-MIR-3910 | 99.95 | 71.13 | 2227 |
| HSA-MIR-381-3P | 99.93 | 71.87 | 2854 |
| HSA-MIR-300 | 99.92 | 71.76 | 2856 |
| HSA-MIR-5195-3P | 99.92 | 70.92 | 1877 |
| HSA-MIR-145-5P | 99.92 | 71.13 | 1836 |
| HSA-MIR-1305 | 99.91 | 71.43 | 3443 |
| HSA-MIR-3671 | 99.90 | 73.04 | 3897 |

### Functional genomics

**gnomAD constraint:** pLI 1.94e-07, LOEUF 0.875, missense Z 0.968 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). [gnomAD](https://gnomad.broadinstitute.org/)

#### Regional missense constraint (gnomAD)

`ENST00000410053` splits into 3 regions with different missense tolerance; **0 are missense-constrained**. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. [gnomAD](https://gnomad.broadinstitute.org/)

| Region (GRCh38) | Missense obs / exp | o/e | Constrained |
| --- | --- | --- | --- |
| 2:179,945,132–179,950,709 | 306 / 296.8 | 1.03 | no |
| 2:179,950,710–179,954,976 | 115 / 169.8 | 0.68 | no |
| 2:179,954,977–179,993,341 | 559 / 602.3 | 0.93 | no |
**DepMap (CRISPR cell-line fitness):** dependent in 99.7% of screened cell lines, common-essential.

**Most-dependent cell lines** *(DepMap gene-effect, lower = stronger; ≤ −0.5 shown)*: MFE-280 (-3.023), RERF-GC-1B (-3.0), NCI-H226 (-2.932), Calu-6 (-2.876), SLR 20 (-2.7), HCC1187 (-2.578), AU565 (-2.461), SK-BR-3 (-2.394), COR-L311 (-2.388), NCI-H747 (-2.376), MCF-7 (-2.371), VCaP (-2.365), 42-MG-BA (-2.339), EFO-21 (-2.284), CCF-STTG1 (-2.276).

### Literature-anchored findings (GeneRIF, showing 6)

- CWC22 connects pre-mRNA splicing and exon junction complex assembly. (PMID:22959432)
- CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly (PMID:22961380)
- The essential splicing factor CWC22 has acquired functions in exon junction complex assembly and nonsense-mediated decay during evolution from single-celled to complex eukaryotes. (PMID:23236153)
- The binding mode of CWC22 to eIF4AIII reveals a facet of how MIF4G domains use their versatile structural frameworks to activate or inhibit DEAD-box proteins. (PMID:24218557)
- Structural and functional insights into CWC27/CWC22 heterodimer linking the exon junction complex to spliceosomes. (PMID:32329775)
- Gene expression network analysis of lymph node involvement in colon cancer identifies AHSA2, CDK10, and CWC22 as possible prognostic markers. (PMID:32345988)

### Cross-species orthologs

**15 orthologs**

| Organism | Symbol | Gene ID |
| --- | --- | --- |
| danio_rerio | cwc22 | ENSDARG00000014008 |
| mus_musculus | Cwc22 | ENSMUSG00000027014 |
| mus_musculus | Cwc22rt6 | ENSMUSG00000079247 |
| mus_musculus | Cwc22rt1 | ENSMUSG00000094125 |
| mus_musculus | Cwc22rt2 | ENSMUSG00000094336 |
| mus_musculus | Cwc22rt7 | ENSMUSG00000095824 |
| mus_musculus | Cwc22rt5 | ENSMUSG00000096337 |
| mus_musculus | Cwc22rt4 | ENSMUSG00000096484 |
| mus_musculus | Cwc22rt3 | ENSMUSG00000096729 |
| rattus_norvegicus | Cwc22 | ENSRNOG00000012651 |
| rattus_norvegicus | LOC134479416 | ENSRNOG00000071808 |
| rattus_norvegicus |  | ENSRNOG00000082394 |
| rattus_norvegicus | LOC134479417 | ENSRNOG00000085537 |
| drosophila_melanogaster | ncm | FBGN0086707 |
| caenorhabditis_elegans |  | WBGENE00002957 |

**Paralogs (1):** NOM1 (ENSG00000146909)

#### Mouse-model phenotypes

Observed phenotypes of the mouse ortholog ([MGI:2136773](https://www.informatics.jax.org/marker/MGI:2136773)) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

| Mouse phenotype (MP) | Records |
| --- | --- |
| abnormal liver morphology | 1 |
| abnormal spleen morphology | 1 |
| hemorrhage | 1 |
| spina bifida | 1 |
| increased circulating aspartate transaminase level | 1 |
| urinary bladder obstruction | 1 |
| increased bone mineral content | 1 |
| preweaning lethality, complete penetrance | 1 |
| cystolithiasis | 1 |
| embryonic lethality prior to organogenesis | 1 |
| prenatal lethality prior to heart atrial septation | 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 |
| --- | --- | --- | --- |
| Musca domestica | [P0DP80](https://www.uniprot.org/uniprotkb/P0DP80/entry) | 99.8% | Diamond |
| Cryptococcus deneoformans JEC21 | [P0CM96](https://www.uniprot.org/uniprotkb/P0CM96/entry) | 99.7% | Diamond |
| Cryptococcus deneoformans B-3501A | [P0CM97](https://www.uniprot.org/uniprotkb/P0CM97/entry) | 99.7% | Diamond |
| Pongo abelii | [Q5RA93](https://www.uniprot.org/uniprotkb/Q5RA93/entry) | 96.0% | Diamond |
| Aspergillus fumigatus Af293 | [Q4WKB9](https://www.uniprot.org/uniprotkb/Q4WKB9/entry) | 92.1% | Diamond |
| Aspergillus nidulans FGSC A4 | [Q5BGP1](https://www.uniprot.org/uniprotkb/Q5BGP1/entry) | 92.1% | Diamond |
| Xenopus laevis | [Q52KN9](https://www.uniprot.org/uniprotkb/Q52KN9/entry) | 88.6% | Diamond |
| Gallus gallus | [Q5ZKA3](https://www.uniprot.org/uniprotkb/Q5ZKA3/entry) | 88.6% | Diamond |
| Caenorhabditis briggsae | [A8WT19](https://www.uniprot.org/uniprotkb/A8WT19/entry) | 87.9% | Diamond |
| Neurospora crassa OR74A | [Q7RX84](https://www.uniprot.org/uniprotkb/Q7RX84/entry) | 77.5% | Diamond |
| Pyricularia oryzae 70-15 | [Q52B63](https://www.uniprot.org/uniprotkb/Q52B63/entry) | 75.7% | Diamond |
| Schizosaccharomyces pombe 972h- | [Q9P6R9](https://www.uniprot.org/uniprotkb/Q9P6R9/entry) | 65.5% | Diamond |
| Mycosarcoma maydis | [Q4PCY0](https://www.uniprot.org/uniprotkb/Q4PCY0/entry) | 65.0% | Diamond |
| Yarrowia lipolytica CLIB122 | [Q6C8C5](https://www.uniprot.org/uniprotkb/Q6C8C5/entry) | 52.4% | Diamond |
| Debaryomyces hansenii CBS767 | [Q6BU84](https://www.uniprot.org/uniprotkb/Q6BU84/entry) | 50.8% | Diamond |
| Candida albicans SC5314 | [Q59XY0](https://www.uniprot.org/uniprotkb/Q59XY0/entry) | 50.7% | Diamond |
| Saccharomyces cerevisiae S288C | [P53333](https://www.uniprot.org/uniprotkb/P53333/entry) | 34.5% | Diamond |
| Eremothecium gossypii ATCC 10895 | [Q751P4](https://www.uniprot.org/uniprotkb/Q751P4/entry) | 33.9% | 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 |
| --- | --- | --- |
| [ZNF385B](/atlas/gene/ZNF385B/) | protein-coding | 151126 |
| [EPCART](/atlas/gene/EPCART/) | ncRNA | 105373767 |
| [MIR1258](/atlas/gene/MIR1258/) | ncRNA | 100302172 |
| [SESTD1](/atlas/gene/SESTD1/) | protein-coding | 91404 |

<a id="protein-Q9HCG8"></a>

## Protein

### Protein identifiers

**Pre-mRNA-splicing factor CWC22 homolog** — `Q9HCG8` (reviewed: Q9HCG8)

**Alternative names:** Nucampholin homolog, fSAPb

**All UniProt accessions (2):** `Q9HCG8`, `B7WP74`

#### UniProt curated annotations — [full annotation on UniProt →](https://www.uniprot.org/uniprotkb/Q9HCG8/entry)

**Function.** Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. Promotes exon-junction complex (EJC) assembly. Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay.

**Subunit / interactions.** Component of the pre-catalytic spliceosome B and the catalytic spliceosome C complexes. Component of the minor spliceosome, which splices U12-type introns. Interacts with EIF4A3 and PRPF19 in an RNA-independent manner. Direct interaction with EIF4A3 is mediated by the MIF4G domain. Full interaction with EIF4A3 occurs only when EIF4A3 is not part of the EJC and prevents EIF4A3 binding to RNA.

**Subcellular location.** Nucleus. Nucleus speckle.

**Similarity.** Belongs to the CWC22 family.

**RefSeq proteins (5):** `NP_001362958`, `NP_001362959`, `NP_001362961`, `NP_001362962`, `NP_065994`*  (*=MANE)

#### Domains & families (InterPro)

| ID | Name | Type |
| --- | --- | --- |
| IPR003890 | MIF4G-like_typ-3 | Domain |
| IPR003891 | Initiation_fac_eIF4g_MI | Domain |
| IPR016024 | ARM-type_fold | Homologous_superfamily |
| IPR050781 | CWC22_splicing_factor | Family |

**Pfam:** `PF02847`, `PF02854`

**UniProt features (79 total):** helix 30, compositionally biased region 11, sequence conflict 7, strand 7, modified residue 5, mutagenesis site 5, turn 5, sequence variant 3, region of interest 3, domain 2, chain 1

### Structure

#### Experimental structures (PDB)

29 structures by resolution:

| PDB | Title | Method | Resolution (Å) |
| --- | --- | --- | --- |
| 4C9B | Crystal structure of eIF4AIII-CWC22 complex | X-RAY DIFFRACTION | 2 |
| 8C6J | Human spliceosomal PM5 C\* complex | ELECTRON MICROSCOPY | 2.8 |
| 7DVQ | Cryo-EM Structure of the Activated Human Minor Spliceosome (minor Bact Complex) | ELECTRON MICROSCOPY | 2.89 |
| 9XTT | Human minor spliceosome branching-completed C complex (after step-I) | ELECTRON MICROSCOPY | 2.92 |
| 6ICZ | Cryo-EM structure of a human post-catalytic spliceosome (P complex) at 3.0 angstrom | ELECTRON MICROSCOPY | 3 |
| 8I0R | The cryo-EM structure of human Bact-I complex | ELECTRON MICROSCOPY | 3 |
| 8I0T | The cryo-EM structure of human Bact-III complex | ELECTRON MICROSCOPY | 3 |
| 8I0V | The cryo-EM structure of human post-Bact complex | ELECTRON MICROSCOPY | 3 |
| 9XU3 | Human minor spliceosome exon-ligation-ready C\* complex (prior to step-II) | ELECTRON MICROSCOPY | 3 |
| 7QTT | Structural organization of a late activated human spliceosome (Baqr, core region) | ELECTRON MICROSCOPY | 3.1 |
| 6YVH | CWC22-CWC27-EIF4A3 Complex | X-RAY DIFFRACTION | 3.19 |
| 6QDV | Human post-catalytic P complex spliceosome | ELECTRON MICROSCOPY | 3.3 |
| 8I0U | The cryo-EM structure of human Bact-IV complex | ELECTRON MICROSCOPY | 3.3 |
| 9FMD | Integrative model of the human post-catalytic spliceosome (P-complex) | ELECTRON MICROSCOPY | 3.3 |
| 6ZYM | Human C Complex Spliceosome - High-resolution CORE | ELECTRON MICROSCOPY | 3.4 |
| 8I0W | The cryo-EM structure of human C complex | ELECTRON MICROSCOPY | 3.4 |
| 5XJC | Cryo-EM structure of the human spliceosome just prior to exon ligation at 3.6 angstrom | ELECTRON MICROSCOPY | 3.6 |
| 7W59 | The cryo-EM structure of human pre-C\*-I complex | ELECTRON MICROSCOPY | 3.6 |
| 7W5A | The cryo-EM structure of human pre-C\*-II complex | ELECTRON MICROSCOPY | 3.6 |
| 5YZG | The Cryo-EM Structure of Human Catalytic Step I Spliceosome (C complex) at 4.1 angstrom … | ELECTRON MICROSCOPY | 4.1 |
| 8I0S | The cryo-EM structure of human Bact-II complex | ELECTRON MICROSCOPY | 4.2 |
| 7W5B | The cryo-EM structure of human C\* complex | ELECTRON MICROSCOPY | 4.3 |
| 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 |
| 7A5P | Human C Complex Spliceosome - Medium-resolution PERIPHERY | ELECTRON MICROSCOPY | 5 |
| 5Z56 | cryo-EM structure of a human activated spliceosome (mature Bact) at 5.1 angstrom. | ELECTRON MICROSCOPY | 5.1 |
| 5MQF | Cryo-EM structure of a human spliceosome activated for step 2 of splicing (C\* complex) | ELECTRON MICROSCOPY | 5.9 |
| 8CH6 | Structure of a late-stage activated spliceosome (BAqr) arrested with a dominant-negative … | ELECTRON MICROSCOPY | 5.9 |
| 5Z57 | Cryo-EM structure of the human activated spliceosome (late Bact) at 6.5 angstrom | ELECTRON MICROSCOPY | 6.5 |

#### Predicted structure (AlphaFold)

| Model | pLDDT | Fraction very-high |
| --- | --- | --- |
| AF-Q9HCG8-F1 | 65.00 | 0.32 |

### Human Protein Atlas

**Protein class:** Predicted intracellular proteins, Essential proteins

**Protein evidence:** Evidence at protein level

**Subcellular location (HPA, imaging):** nuclear speckles; 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 | 39, 61, 107, 786, 829 |

#### Mutagenesis-validated functional residues (5)

| Position | Phenotype |
| --- | --- |
| 168 | no effect on eif4a3 incorporation into ejcs. |
| 171–174 | loss of eif4a3-binding. |
| 171–172 | loss of eif4a3-binding. |
| 331 | decreased eif4a3-binding; when associated with a-334. |
| 334 | decreased eif4a3-binding; when associated with a-331. |

## 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: 127** (showing top):
`RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP`, `REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA`, `GOBP_RNA_SPLICING`, `REACTOME_MRNA_SPLICING`, `WANG_TARGETS_OF_MLL_CBP_FUSION_DN`, `GOBP_REGULATION_OF_MRNA_SPLICING_VIA_SPLICEOSOME`, `GOBP_REGULATION_OF_RNA_SPLICING`, `REACTOME_METABOLISM_OF_RNA`, `GOCC_U2_TYPE_SPLICEOSOMAL_COMPLEX`, `GOCC_NUCLEAR_SPECK`, `GOCC_PRECATALYTIC_SPLICEOSOME`, `GOCC_NUCLEAR_BODY`, `GOCC_RIBONUCLEOPROTEIN_GRANULE`, `GOCC_CATALYTIC_STEP_2_SPLICEOSOME`, `GOCC_SPLICEOSOMAL_COMPLEX`

**GO Biological Process (4):**
mRNA splicing, via spliceosome (GO:0000398), regulation of mRNA splicing, via spliceosome (GO:0048024), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

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

**GO Cellular Component (8):**
nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), nuclear speck (GO:0016607), U2-type precatalytic spliceosome (GO:0071005), U2-type catalytic step 1 spliceosome (GO:0071006), U2-type catalytic step 2 spliceosome (GO:0071007), catalytic step 2 spliceosome (GO:0071013)

#### 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

27 GO namespaces:

| Category | Terms |
| --- | --- |
| U2-type spliceosomal complex | 3 |
| U2 snRNP | 3 |
| RNA processing | 2 |
| U6 snRNP | 2 |
| RNA splicing, via transesterification reactions with bulged adenosine as nucleophile | 1 |
| mRNA processing | 1 |
| mRNA splicing, via spliceosome | 1 |
| regulation of RNA splicing | 1 |
| regulation of mRNA processing | 1 |
| mRNA metabolic process | 1 |
| nucleic acid binding | 1 |
| binding | 1 |
| intracellular membrane-bounded organelle | 1 |
| nuclear lumen | 1 |
| cellular anatomical structure | 1 |
| nuclear protein-containing complex | 1 |
| ribonucleoprotein complex | 1 |
| nuclear ribonucleoprotein granule | 1 |
| U1 snRNP | 1 |
| U4/U6 x U5 tri-snRNP complex | 1 |
| precatalytic spliceosome | 1 |
| catalytic step 1 spliceosome | 1 |
| catalytic step 2 spliceosome | 1 |
| Prp19 complex | 1 |
| spliceosomal complex | 1 |
| U5 snRNP | 1 |
| catalytic complex | 1 |

#### Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

| GO term | NS | Evidence |
| --- | --- | --- |
| [mRNA splicing, via spliceosome](https://amigo.geneontology.org/amigo/term/GO:0000398) | BP | direct assay |
| [U2-type catalytic step 1 spliceosome](https://amigo.geneontology.org/amigo/term/GO:0071006) | CC | direct assay |
| [U2-type catalytic step 2 spliceosome](https://amigo.geneontology.org/amigo/term/GO:0071007) | CC | direct assay |
| [U2-type precatalytic spliceosome](https://amigo.geneontology.org/amigo/term/GO:0071005) | CC | direct assay |
| [catalytic step 2 spliceosome](https://amigo.geneontology.org/amigo/term/GO:0071013) | CC | direct assay |
| [nuclear speck](https://amigo.geneontology.org/amigo/term/GO:0016607) | CC | direct assay |
| [nucleus](https://amigo.geneontology.org/amigo/term/GO:0005634) | CC | direct assay |
| [spliceosomal complex](https://amigo.geneontology.org/amigo/term/GO:0005681) | CC | direct assay |
| [RNA binding](https://amigo.geneontology.org/amigo/term/GO:0003723) | MF | direct assay |

### Protein interactions and networks

#### STRING

showing 15 of 1,565 interactions by confidence (×1000):

| Protein A | Protein B | Partner UniProt | Score |
| --- | --- | --- | --- |
| CWC22 | CWC25 | Q9NXE8 | 747 |
| CWC22 | YJU2 | Q9BW85 | 730 |
| CWC22 | SLU7 | O95391 | 694 |
| CWC22 | CWC27 | Q6UX04 | 693 |
| CWC22 | XAB2 | Q9HCS7 | 653 |
| CWC22 | DHX8 | Q14562 | 650 |
| CWC22 | CDC5L | Q99459 | 647 |
| CWC22 | MAGOHB | Q96A72 | 645 |
| CWC22 | MAGOH | P50606 | 645 |
| CWC22 | PRPF18 | Q99633 | 635 |
| CWC22 | BUD13 | Q9BRD0 | 630 |
| CWC22 | RNF113A | O15541 | 628 |
| CWC22 | EIF4A3 | P38919 | 628 |
| CWC22 | DHX38 | Q92620 | 619 |
| CWC22 | EFTUD2 | Q15029 | 607 |

#### IntAct

Human interaction partners of CWC22 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

| Partner | Interaction type | MIscore | Records |
| --- | --- | --- | --- |
| EIF4A3 | direct interaction | 0.860 | 5 |
| KLHL2 | physical association | 0.560 | 3 |
| PTPN21 | physical association | 0.560 | 3 |
| FAM32A | physical association | 0.510 | 2 |
| FRG1 | physical association | 0.510 | 2 |
| CFTR | physical association | 0.370 | 1 |
| EXOSC8 | physical association | 0.000 | 1 |
| YWHAB | physical association | 0.000 | 1 |

**BioGRID (170 interactions; top human partners by supporting records):** EIF4A3 (Affinity Capture-Western; 11 records), FAM32A (Two-hybrid; 4 records), CAMKV (Affinity Capture-MS; 3 records), CTDSP2 (Affinity Capture-MS; 3 records), DENND2D (Affinity Capture-MS; 3 records), DOK4 (Affinity Capture-MS; 3 records), EDA (Affinity Capture-MS; 3 records), FAM9A (Affinity Capture-MS; 3 records), FMR1NB (Affinity Capture-MS; 3 records), FRG1 (Two-hybrid; 3 records), GPR183 (Affinity Capture-MS; 3 records), PTGER3 (Affinity Capture-MS; 3 records), VTI1B (Affinity Capture-MS; 3 records), C11orf57 (Affinity Capture-MS; 2 records), EPB41L2 (Affinity Capture-MS; 2 records)

#### Protein complexes (CORUM) (2)

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

2 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 |
| Spliceosome, C complex | 39 | MAGOH, PPWD1, RBM8A, SNRPF, SNRPG, SYF2, PPIE, SNRPB2, SNRPA1, BCAS2, BUD31, CWC25, SNRPD2, SNRPD3, CASC3, EIF4A3, PRPF19, SNRPD1, SNRPE, YJU2, SRRM2, XAB2, CWC22, RBM22, SNRNP200, AQR, CWC15, EFTUD2, ISY1, PPIG, CDC40, CDC5L, DHX38, PLRG1, PPIL1, PRPF8, SNRPB, SNW1, CRNKL1 |

## Disease & clinical

### Genetic variants

**Variant evidence for CWC22:** [153 ClinVar records](#clinvar) (0 pathogenic / likely pathogenic); [6 GWAS associations](#gwas-assoc).

#### ClinVar

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

| Classification | Count (floor) |
| --- | --- |
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 122 |
| Likely benign | 8 |
| Benign | 4 |

#### SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 40 predictions of 1,290):

| Position(s) | Effect | Δscore | Sites |
| --- | --- | --- | --- |
| 2:179945722 | acceptor_gain | 1.0000 |  |
| 2:179950927–179950928 | acceptor_loss | 1.0000 | 6 |
| 2:179952469–179952470 | donor_loss | 1.0000 | 5 |
| 2:179952474 | donor_gain | 1.0000 |  |
| 2:179954203–179954204 | donor_loss | 1.0000 | 5 |
| 2:179954358–179954359 | acceptor_loss | 1.0000 | 6 |
| 2:179954361 | acceptor_gain | 1.0000 |  |
| 2:179964545–179964546 | donor_loss | 1.0000 | 5 |
| 2:179964629–179964630 | acceptor_loss | 1.0000 | 6 |
| 2:179965876–179965877 | donor_loss | 1.0000 | 4 |

#### AlphaMissense

2,505 missense substitutions predicted likely pathogenic (of 6,045 scored), across 478 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 |
| --- | --- | --- | --- |
| M492 | 9 | 0.997 | 1.000 |
| M335 | 9 | 0.965 | 0.997 |
| M479 | 9 | 0.874 | 0.986 |
| H474 | 8 | 0.999 | 1.000 |
| N171 | 8 | 0.998 | 1.000 |
| D446 | 8 | 0.998 | 0.999 |
| D495 | 8 | 0.998 | 0.999 |
| N629 | 8 | 0.998 | 1.000 |
| H537 | 8 | 0.997 | 1.000 |
| N189 | 8 | 0.995 | 1.000 |
| F626 | 8 | 0.995 | 1.000 |
| S466 | 8 | 0.992 | 1.000 |
| F211 | 8 | 0.991 | 1.000 |
| F385 | 8 | 0.989 | 1.000 |
| F340 | 8 | 0.987 | 0.999 |
| N546 | 8 | 0.986 | 1.000 |
| D388 | 8 | 0.985 | 0.997 |
| F582 | 8 | 0.985 | 0.999 |
| H368 | 8 | 0.984 | 0.998 |
| H324 | 8 | 0.983 | 0.998 |

### HPA cancer prognostics

**RNA cancer specificity:** Low cancer specificity

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

3 prognostic cancer types:

| Cancer | Prognostic | p-value |
| --- | --- | --- |
| Kidney Renal Clear Cell Carcinoma (TCGA) | favorable | 6.3e-06 |
| Kidney Renal Clear Cell Carcinoma (validation) | favorable | 0.000344 |
| Kidney Chromophobe (TCGA) | unfavorable | 0.00098 |

### Disease associations

**OMIM:** gene `MIM:615186` | disease phenotypes: 

#### GWAS associations

6 associations:

| Study | Trait | p-value |
| --- | --- | --- |
| GCST004904_17 | Body mass index | 2e-13 |
| GCST010988_474 | Adult body size | 3e-13 |
| GCST004904_208 | Body mass index | 5e-8 |
| GCST007201_315 | Schizophrenia | 1e-6 |
| GCST010396_150 | Gut microbiota (bacterial taxa, hurdle binary method) | 1e-6 |
| GCST009391_844 | Metabolite levels | 5e-6 |

#### EFO canonical traits (from GWAS)

3 canonical traits:

| EFO ID | Trait name |
| --- | --- |
| EFO:0004340 | body mass index |
| EFO:0010400 | triacylglycerol 46:0 measurement |
| EFO:0007874 | gut microbiome measurement |

## Drugs & pharmacology

### Drug and pharmacology data

**Is drug target: yes**

**ChEMBL targets (1):** CHEMBL5724778 (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 |
| --- | --- | --- | --- | --- |
| 7.82 | Kd | 15 | nM | [MOLIBRESIB](https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1232461/) |
| 7.70 | IC50 | 20 | nM | [MOLIBRESIB](https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1232461/) |

#### 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 | [2179153](https://pubchem.ncbi.nlm.nih.gov/bioassay/2179153/): Binding affinity against CWC22 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis | kd | 0.0150 | uM |

#### CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

| Chemical | Actions (top 5) | PubMed papers |
| --- | --- | --- |
| Valproic Acid | decreases expression, affects expression, decreases methylation, affects cotreatment | 7 |
| sodium arsenite | affects methylation, decreases expression, increases abundance, increases expression | 4 |
| trichostatin A | affects cotreatment, decreases expression | 3 |
| perfluorooctane sulfonic acid | decreases expression | 2 |
| Phenylmercuric Acetate | affects cotreatment, decreases expression | 2 |
| aristolochic acid I | decreases expression | 1 |
| FR900359 | affects phosphorylation | 1 |
| TAK-243 | decreases sumoylation | 1 |
| dicrotophos | decreases expression | 1 |
| arsenite | decreases reaction, affects binding | 1 |
| zinc chromate | increases abundance, increases expression | 1 |
| coumarin | affects phosphorylation | 1 |
| chromium hexavalent ion | increases expression, increases abundance | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | decreases expression, affects cotreatment | 1 |
| ICG 001 | decreases expression | 1 |
| abrine | increases expression | 1 |
| dorsomorphin | affects cotreatment, decreases expression | 1 |
| jinfukang | affects cotreatment, decreases expression | 1 |
| (+)-JQ1 compound | decreases expression | 1 |
| Arsenic | increases abundance, increases expression | 1 |
| Benzo(a)pyrene | decreases methylation | 1 |
| Cisplatin | affects cotreatment, decreases expression | 1 |
| Copper | increases expression | 1 |
| Formaldehyde | decreases expression | 1 |
| Ribonucleotides | affects binding | 1 |
| Thiram | increases expression | 1 |
| Tobacco Smoke Pollution | increases expression | 1 |
| Cyclosporine | increases expression | 1 |
| Asbestos, Crocidolite | 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 |
| --- | --- | --- | --- |
| CHEMBL5697219 | Binding | Inhibition of CWC22 (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.

#### Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CWC22 across ~30M SureChEMBL compounds — [explore on Sugi Predict](https://sugi.bio/predict/target/CWC22/).

## Related Atlas pages

*No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.*