DCAF13

Summary

DCAF13 (DDB1 and CUL4 associated factor 13, HGNC:24535) is a protein-coding gene on chromosome 8q22.3, encoding DDB1- and CUL4-associated factor 13 (Q9NV06). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

Enables nuclear estrogen receptor binding activity and ubiquitin-like ligase-substrate adaptor activity. Involved in several processes, including decidualization; epigenetic programming in the zygotic pronuclei; and spindle assembly involved in female meiosis. Located in several cellular components, including centrosome; cytosol; and nuclear lumen. Part of Cul4-RING E3 ubiquitin ligase complex.

Source: NCBI Gene 25879 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neuromuscular disease (Limited, GenCC)
• Clinical variants (ClinVar): 110 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_015420

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24535
Approved symbol	DCAF13
Name	DDB1 and CUL4 associated factor 13
Location	8q22.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP564O0463, Gm83, HSPC064, Sof1
Ensembl gene	ENSG00000164934
Ensembl biotype	protein_coding
OMIM	616196
Entrez	25879

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 3 retained_intron

ENST00000297579, ENST00000518554, ENST00000519682, ENST00000521716, ENST00000521971, ENST00000521999, ENST00000611541, ENST00000612750, ENST00000616836, ENST00000875739, ENST00000875740, ENST00000875741, ENST00000920238, ENST00000920239, ENST00000947280, ENST00000947281

RefSeq mRNA: 2 — MANE Select: NM_015420 NM_001416065, NM_015420

CCDS: CCDS34934

Canonical transcript exons

ENST00000612750 — 11 exons

Exon	Start	End
ENSE00002099768	103442795	103443453
ENSE00003495844	103426056	103426145
ENSE00003508735	103420975	103421082
ENSE00003519411	103420264	103420463
ENSE00003546576	103427097	103427252
ENSE00003599775	103441455	103441618
ENSE00003612790	103440136	103440271
ENSE00003668858	103432659	103432741
ENSE00003669432	103435626	103435790
ENSE00003712455	103430612	103430689
ENSE00003731195	103415386	103415516

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 96.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.9409 / max 1240.9486, expressed in 1815 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90119	42.4296	1809
205282	0.9326	587
90118	0.5786	181

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.95	gold quality
oocyte	CL:0000023	96.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.64	gold quality
colonic epithelium	UBERON:0000397	95.26	gold quality
esophagus squamous epithelium	UBERON:0006920	95.10	gold quality
tibia	UBERON:0000979	94.88	gold quality
parietal pleura	UBERON:0002400	94.56	gold quality
ventricular zone	UBERON:0003053	94.48	gold quality
visceral pleura	UBERON:0002401	94.22	gold quality
gingival epithelium	UBERON:0001949	94.08	gold quality
germinal epithelium of ovary	UBERON:0001304	93.75	gold quality
ganglionic eminence	UBERON:0004023	93.67	gold quality
epithelium of nasopharynx	UBERON:0001951	93.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.53	gold quality
cortical plate	UBERON:0005343	93.49	gold quality
gingiva	UBERON:0001828	93.47	gold quality
pleura	UBERON:0000977	92.97	gold quality
adrenal tissue	UBERON:0018303	92.95	gold quality
palpebral conjunctiva	UBERON:0001812	92.70	gold quality
islet of Langerhans	UBERON:0000006	92.63	gold quality
sperm	CL:0000019	92.48	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.32	gold quality
stromal cell of endometrium	CL:0002255	91.78	gold quality
oral cavity	UBERON:0000167	91.53	gold quality
endometrium	UBERON:0001295	91.52	gold quality
colonic mucosa	UBERON:0000317	91.22	gold quality
calcaneal tendon	UBERON:0003701	90.93	gold quality
bronchial epithelial cell	CL:0002328	90.89	gold quality
amniotic fluid	UBERON:0000173	90.40	gold quality
rectum	UBERON:0001052	90.21	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	20.20
E-CURD-112	yes	9.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting DCAF13, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 12)

• This study suggests that non-synonymous WDSOF1 polymorphisms play a role in the genetic susceptibility to osteoporosis. (PMID:20601284)
• our findings revealed that the overexpression of DCAF13 in hepatocellular carcinoma was significantly associated with poor survival and may participate in the regulation of cell cycle progression (PMID:28631558)
• Two novel variants in the DCAF13 and NOV genes were identified that are associated with familial cortical myoclonic tremor with epilepsy in a Chinese pedigree. (PMID:30003937)
• The DCAF13 deficiency resulted in pre-rRNA accumulation in oocytes, whereas the total mRNA level was not altered. Further exploration showed that DCAF13 participated in the 18S rRNA processing in growing oocytes. (PMID:30283081)
• DCAF13 promotes triple-negative breast cancer metastasis by mediating DTX3 mRNA degradation. (PMID:33300431)
• Doxorubicin promotes breast cancer cell migration and invasion via DCAF13. (PMID:34775691)
• DCAF13 promotes breast cancer cell proliferation by ubiquitin inhibiting PERP expression. (PMID:35178836)
• DCAF13 is essential for the pathogenesis of preeclampsia through its involvement in endometrial decidualization. (PMID:35932979)
• A biallelic variant of DCAF13 implicated in a neuromuscular disorder in humans. (PMID:36797467)
• A multidimensional pan-cancer analysis of DCAF13 and its protumorigenic effect in lung adenocarcinoma. (PMID:36884358)
• CRL4[DCAF13] E3 ubiquitin ligase targets MeCP2 for degradation to prevent DNA hypermethylation and ensure normal transcription in growing oocytes. (PMID:38578457)
• DCAF13 promotes ovarian cancer progression by activating FRAS1-mediated FAK signaling pathway. (PMID:39367995)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dcaf13	ENSDARG00000002267
mus_musculus	Dcaf13	ENSMUSG00000022300
rattus_norvegicus	Dcaf13	ENSRNOG00000004301
drosophila_melanogaster	CG7275	FBGN0036500
caenorhabditis_elegans		WBGENE00022742

Protein

Protein identifiers

DDB1- and CUL4-associated factor 13 — Q9NV06 (reviewed: Q9NV06)

Alternative names: WD repeat and SOF domain-containing protein 1

All UniProt accessions (5): A0A087WT20, A0A087X1F8, B3KME9, E5RHM4, Q9NV06

UniProt curated annotations — full annotation on UniProt →

Function. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Participates in the 18S rRNA processing in growing oocytes, being essential for oocyte nonsurrounded nucleolus (NSN) to surrounded nucleolus (SN) transition. Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex that plays a key role in embryo preimplantation and is required for normal meiotic cycle progression in oocytes. Acts as a maternal factor that regulates oocyte and zygotic chromatin tightness during maternal to zygotic transition. Also involved in the transformation of the endometrium into the decidua, known as decidualization, providing a solid foundation for implantation of blastocysts. Recognizes the histone methyltransferases SUV39H1 and SUV39H2 and directs them to polyubiquitination and proteasomal degradation, which facilitates the H3K9me3 removal and early zygotic gene expression, essential steps for progressive genome reprogramming and the establishment of pluripotency during preimplantation embryonic development. Supports the spindle assembly and chromosome condensation during oocyte meiotic division by targeting the polyubiquitination and degradation of PTEN, a lipid phosphatase that inhibits PI3K pathway as well as oocyte growth and maturation. Targets PMP22 for polyubiquitination and proteasomal degradation.

Subunit / interactions. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Component of the DCX(DCAF13) E3 ubiquitin ligase complex, at least composed of CUL4 (CUL4A or CUL4B), DDB1, DCAF13 and RBX1. Interacts (via WD40 domain) with DDB1. Interacts with ESR1 and LATS1.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Expressed in the endometrium during decidualization. Expression is down-regulated in preeclampsia decidual tissues.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the WD repeat DCAF13/WDSOF1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NV06-1	1	yes
Q9NV06-2	2

RefSeq proteins (2): NP_001402994, NP_056235* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR007287	Sof1	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR051733	WD_repeat_DCAF13/WDSOF1	Family

Pfam: PF00400, PF04158

UniProt features (17 total): repeat 7, sequence conflict 3, splice variant 2, sequence variant 2, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7MQA	ELECTRON MICROSCOPY	2.7
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NV06-F1	92.84	0.82

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 (1): 49

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-8951664	Neddylation

MSigDB gene sets: 202 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_MATURATION_OF_SSU_RRNA, GOBP_GROWTH, GOBP_OOGENESIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_DECIDUALIZATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_ORGANELLE_FISSION, MYCMAX_01, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS

GO Biological Process (11): maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462), oocyte growth (GO:0001555), rRNA processing (GO:0006364), spindle assembly involved in female meiosis (GO:0007056), protein ubiquitination (GO:0016567), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), epigenetic programming in the zygotic pronuclei (GO:0044725), decidualization (GO:0046697), female gamete generation (GO:0007292), ribosome biogenesis (GO:0042254), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898)

GO Molecular Function (4): RNA binding (GO:0003723), nuclear estrogen receptor binding (GO:0030331), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (9): nucleoplasm (GO:0005654), nucleolus (GO:0005730), centrosome (GO:0005813), cytosol (GO:0005829), cell junction (GO:0030054), small-subunit processome (GO:0032040), Cul4-RING E3 ubiquitin ligase complex (GO:0080008), nucleus (GO:0005634), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	2
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
developmental process involved in reproduction	2
nuclear lumen	2
maturation of SSU-rRNA	1
developmental cell growth	1
oocyte development	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
female meiotic nuclear division	1
meiotic spindle assembly	1
protein modification by small protein conjugation	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
epigenetic programming of gene expression	1
maternal placenta development	1
tissue development	1
gamete generation	1
ribonucleoprotein complex biogenesis	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
negative regulation of intracellular signal transduction	1
nucleic acid binding	1
nuclear receptor binding	1
enzyme-substrate adaptor activity	1
binding	1
intracellular membraneless organelle	1
centriole	1
microtubule organizing center	1
cytoplasm	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
cullin-RING ubiquitin ligase complex	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

2357 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCAF13	CUL4B	Q13620	617
DCAF13	WDR12	Q9GZL7	557
DCAF13	RBX1	P62877	536
DCAF13	BOP1	Q14137	532
DCAF13	SLC25A32	Q9H2D1	515
DCAF13	RIMS2	Q9UQ26	507
DCAF13	PTEN	P60484	495
DCAF13	FAM163A	Q96GL9	480
DCAF13	DCAF1	Q9Y4B6	449
DCAF13	EIF4E3	Q8N5X7	447
DCAF13	MRPS23	Q9Y3D9	446
DCAF13	BYSL	Q13895	431
DCAF13	TMEM74	Q96NL1	428
DCAF13	UTP4	Q969X6	422
DCAF13	DDB1	Q16531	420

IntAct

97 interactions, top by confidence:

A	B	Type	Score
S100B	S100A4	psi-mi:“MI:0914”(association)	0.870
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
PDCL3	PEX7	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT5	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT7	TXNDC9	psi-mi:“MI:0914”(association)	0.640
WDR83	SH2B2	psi-mi:“MI:0914”(association)	0.530
HSP90AA1	EDRF1	psi-mi:“MI:0914”(association)	0.530
CCT7	PEX7	psi-mi:“MI:0914”(association)	0.530
DCAF5	PFDN6	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ESR1	LATS1	psi-mi:“MI:0914”(association)	0.500
ESR1	DCAF13	psi-mi:“MI:0915”(physical association)	0.500
DCAF13	CHEK2	psi-mi:“MI:0915”(physical association)	0.400
DCAF13	TK1	psi-mi:“MI:0915”(physical association)	0.370
DCAF13	WARS1	psi-mi:“MI:0915”(physical association)	0.370
ATM	RBM47	psi-mi:“MI:0914”(association)	0.350
NDE1	AMZ2	psi-mi:“MI:0914”(association)	0.350
Set	ZKSCAN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (394): DCAF13 (Affinity Capture-MS), DCAF13 (Affinity Capture-MS), DCAF13 (Co-fractionation), DCAF13 (Co-fractionation), DCAF13 (Co-fractionation), DCAF13 (Co-fractionation), DCAF13 (Co-fractionation), DCAF13 (Co-fractionation), DCAF13 (Co-fractionation), DCAF13 (Co-fractionation), DCAF13 (Co-fractionation), DCAF13 (Co-fractionation), DCAF13 (Co-fractionation), DCAF13 (Co-fractionation), TBL3 (Co-fractionation)

ESM2 similar proteins: A2RRU3, A7MB12, A8QBF3, A8WVX8, A8XYW9, O14021, O43071, O74340, O74879, O94365, P20053, P27133, P27766, P33750, P39984, P40055, P40968, P91341, Q04305, Q0VA16, Q10051, Q32LB0, Q3MKM6, Q3TWF6, Q59RH5, Q5EB92, Q5F3D7, Q5R4T8, Q5REE0, Q5XGE2, Q5ZLK1, Q6CSI1, Q6GPP0, Q6NVS5, Q6PAC3, Q7KWL3, Q7S7N3, Q7ZW33, Q7ZXZ2, Q7ZYQ6

Diamond homologs: A4IIX9, D9N129, F1DLK1, O74184, P38262, P41318, Q3MKM6, Q3MV14, Q4IBR4, Q54HW5, Q5R4T8, Q5R650, Q6DDF0, Q6FLI3, Q7RZI0, Q8CBE3, Q9BYB4, Q9EQ15, Q9NV06, Q9Y2I8, O74340, P33750, Q2UGK1, Q5ZLK1, Q6NVS5, Q6PAC3, Q7KWL3, Q7ZYQ6, Q803X4, B0W517, E3LB80, O16023, O43071, O75530, Q24338, Q26458, Q28DT7, Q2KJJ5, Q3SZ25, Q54JS5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 125 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
Formation of tubulin folding intermediates by CCT/TriC	5	27.8×	2e-04
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	5	26.8×	2e-04
Prefoldin mediated transfer of substrate to CCT/TriC	5	25.9×	2e-04
Chaperonin-mediated protein folding	5	19.8×	7e-04
Protein folding	5	17.1×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	6	40.0×	5e-06
chromosome segregation	6	9.5×	5e-03
protein stabilization	11	6.7×	2e-04
protein folding	7	6.6×	9e-03
cell division	11	4.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	76
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4075897	GRCh37/hg19 8q22.3(chr8:104418038-105005666)x1	Pathogenic

SpliceAI

2061 predictions. Top by Δscore:

Variant	Effect	Δscore
8:103414781:TA:T	donor_loss	1.0000
8:103414782:A:AC	donor_gain	1.0000
8:103414782:ACC:A	donor_loss	1.0000
8:103414783:C:CC	donor_gain	1.0000
8:103414783:C:CT	donor_loss	1.0000
8:103414783:CCGG:C	donor_gain	1.0000
8:103415512:GAGAG:G	donor_gain	1.0000
8:103415514:GAG:G	donor_gain	1.0000
8:103415517:G:A	donor_loss	1.0000
8:103415517:G:GG	donor_gain	1.0000
8:103415518:T:A	donor_loss	1.0000
8:103415522:A:G	donor_gain	1.0000
8:103420262:A:AG	acceptor_gain	1.0000
8:103420263:G:GG	acceptor_gain	1.0000
8:103420974:GGTTA:G	acceptor_gain	1.0000
8:103421078:TCACT:T	donor_gain	1.0000
8:103421079:CACT:C	donor_gain	1.0000
8:103421080:ACT:A	donor_gain	1.0000
8:103421081:CT:C	donor_gain	1.0000
8:103421081:CTG:C	donor_loss	1.0000
8:103421082:TGTA:T	donor_loss	1.0000
8:103421083:G:GG	donor_gain	1.0000
8:103421084:TAA:T	donor_loss	1.0000
8:103421085:A:AC	donor_loss	1.0000
8:103421086:AG:A	donor_loss	1.0000
8:103426142:A:T	donor_gain	1.0000
8:103427223:A:G	donor_gain	1.0000
8:103430610:A:AG	acceptor_gain	1.0000
8:103430611:G:GG	acceptor_gain	1.0000
8:103430611:GAC:G	acceptor_gain	1.0000

AlphaMissense

2959 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:103427143:C:A	A172D	0.999
8:103432692:T:A	W246R	0.999
8:103432692:T:C	W246R	0.999
8:103435741:A:C	S301R	0.999
8:103435743:T:A	S301R	0.999
8:103435743:T:G	S301R	0.999
8:103440239:T:A	W352R	0.999
8:103440239:T:C	W352R	0.999
8:103420447:G:A	G85E	0.998
8:103420984:T:A	W94R	0.998
8:103420984:T:C	W94R	0.998
8:103426083:T:A	W136R	0.998
8:103426083:T:C	W136R	0.998
8:103427169:T:A	W181R	0.998
8:103427169:T:C	W181R	0.998
8:103430627:A:C	S214R	0.998
8:103430629:T:A	S214R	0.998
8:103430629:T:G	S214R	0.998
8:103432726:C:A	A257E	0.998
8:103432732:A:T	E259V	0.998
8:103435691:C:A	A284E	0.998
8:103435742:G:T	S301I	0.998
8:103435744:T:C	F302L	0.998
8:103435746:C:A	F302L	0.998
8:103435746:C:G	F302L	0.998
8:103440182:T:A	W333R	0.998
8:103440182:T:C	W333R	0.998
8:103440216:C:T	S344F	0.998
8:103427233:T:A	V202D	0.997
8:103427243:C:A	N205K	0.997

dbSNP variants (sampled 300 via entrez): RS1000085552 (8:103436177 G>T), RS1000097637 (8:103441955 C>G,T), RS1000137960 (8:103435902 G>A), RS1000173092 (8:103440613 C>T), RS1000220078 (8:103418703 A>G), RS1000300944 (8:103442231 A>G), RS1000309540 (8:103422796 T>A,C), RS1000361079 (8:103428423 T>G), RS1000422463 (8:103413688 GT>G,GTT), RS1000570817 (8:103419190 G>A), RS1000586428 (8:103424008 C>A,T), RS1000742826 (8:103430236 C>G,T), RS1000779586 (8:103424945 A>C,T), RS1001006881 (8:103417780 T>G), RS1001077394 (8:103443933 CAGTT>C)

Disease associations

OMIM: gene MIM:616196 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neuromuscular disease	Limited	Autosomal recessive

Mondo (1): neuromuscular disease (MONDO:0019056)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009468	Neuromuscular Diseases	C10.668

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
Copper	affects binding, decreases expression, increases expression	2
Tretinoin	decreases expression	2
Valproic Acid	decreases methylation, increases expression, affects expression	2
Aflatoxin B1	affects cotreatment, decreases expression, increases methylation	2
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
kojic acid	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
nivalenol	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
NSC 689534	affects binding, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Bortezomib	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	decreases expression, increases abundance, affects cotreatment	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Disulfiram	decreases expression, affects binding	1
Estradiol	increases expression	1
Hydrogen Peroxide	affects expression	1
Lead	affects expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00331656	PHASE4	UNKNOWN	Comparative Study of Non-Invasive Mask Ventilation vs Cuirass Ventilation in Patients With Acute Respiratory Failure.
NCT00994552	PHASE4	UNKNOWN	Comparison of Pressure Support and Pressure Control Ventilation in Chronic Respiratory Failure
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00942227	PHASE3	COMPLETED	The Value of Traction in Treatment of Lumbar Radiculopathy
NCT00979108	PHASE3	COMPLETED	The Value of Traction in the Treatment of Cervical Radiculopathy
NCT01826487	PHASE3	COMPLETED	Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
NCT02090959	PHASE3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
NCT02436096	PHASE3	COMPLETED	A Study to Evaluate eFFIcacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With fibRoMyalgia
NCT02829814	PHASE3	TERMINATED	Repeat of: A Study to Evaluate Efficacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With Fibromyalgia
NCT03179631	PHASE3	COMPLETED	Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
NCT05126758	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT05156320	PHASE3	COMPLETED	Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam
NCT05337553	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
NCT05626855	PHASE3	ACTIVE_NOT_RECRUITING	Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab
NCT06672237	PHASE3	RECRUITING	A Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT01074359	PHASE2	TERMINATED	Safety and Efficacy Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation
NCT01371149	PHASE2	COMPLETED	Patient -Ventilator Interaction in Chronic Respiratory Failure
NCT02022072	PHASE2	TERMINATED	Evaluation of Vital Capacity
NCT03127514	PHASE2	COMPLETED	AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT03406780	PHASE2	COMPLETED	A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT03921528	PHASE2	COMPLETED	An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT06339580	PHASE2	RECRUITING	Assessment of Volume-targeted Ventilation in Patients With Neuromuscular Disease
NCT07071935	PHASE2	NOT_YET_RECRUITING	A Clinical Trial of Early Ventilation in Amyotrophic Lateral Sclerosis (EVENT ALS)
NCT07287189	PHASE2	RECRUITING	Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients
NCT00252252	PHASE1	COMPLETED	AutoVPAP Versus VPAP; Assessment of Sleep and Ventilation
NCT01560741	PHASE1	UNKNOWN	Telemedicine and Ventilator Titration in Chronic Respiratory Patients Initiating Non-invasive Ventilation
NCT01621984	PHASE1	COMPLETED	Therapeutic Riding and Neuromuscular Disease
NCT01758510	PHASE1	COMPLETED	Safety Study of HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis
NCT03440034	PHASE1	COMPLETED	Study of Pioglitazone in Sporadic Inclusion Body Myositis
NCT05730842	PHASE1	COMPLETED	Absorption, Metabolism, Excretion and Absolute Bioavailability of EDG-5506 in Healthy Volunteers
NCT03272802	PHASE2/PHASE3	UNKNOWN	Treatment Effect of Edaravone in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00860951	PHASE1/PHASE2	COMPLETED	P300 Brain Computer Interface Keyboard to Operate Assistive Technology
NCT02362425	PHASE1/PHASE2	COMPLETED	Antioxidant Therapy in RYR1-Related Congenital Myopathy
NCT00001201	Not specified	COMPLETED	Evaluation of Neuromuscular Disease
NCT00002044	Not specified	COMPLETED	A Pilot Study To Evaluate the Effect of Retrovir (Zidovudine: AZT) in the Treatment of Human Immunodeficiency Virus (HIV) Associated Dementia and Neuromuscular Diseases
NCT00004553	Not specified	COMPLETED	Electromyography to Diagnose Neuromuscular Disorders
NCT00015470	Not specified	COMPLETED	Diagnostic Evaluation of Patients With Neuromuscular Disease
NCT00017745	Not specified	COMPLETED	Phenotype/Genotype Correlations in Neuromuscular Disorders
NCT00695591	Not specified	COMPLETED	Home Sleep Testing in Neuromuscular Disease Patients