CDCA7L

Summary

CDCA7L (cell division cycle associated 7 like, HGNC:30777) is a protein-coding gene on chromosome 7p15.3, encoding Cell division cycle-associated 7-like protein (Q96GN5). Plays a role in transcriptional regulation as a repressor that inhibits monoamine oxidase A (MAOA) activity and gene expression by binding to the promoter.

Acts upstream of or within positive regulation of cell population proliferation. Located in cytosol; fibrillar center; and nucleoplasm.

Source: NCBI Gene 55536 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 249 total — 33 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_018719

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30777
Approved symbol	CDCA7L
Name	cell division cycle associated 7 like
Location	7p15.3
Locus type	gene with protein product
Status	Approved
Aliases	RAM2, R1, JPO2
Ensembl gene	ENSG00000164649
Ensembl biotype	protein_coding
OMIM	609685
Entrez	55536

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 21 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000356195, ENST00000373934, ENST00000406877, ENST00000435031, ENST00000435717, ENST00000447180, ENST00000457951, ENST00000465490, ENST00000488845, ENST00000489669, ENST00000904741, ENST00000904742, ENST00000934289, ENST00000934290, ENST00000934291, ENST00000934292, ENST00000934293, ENST00000934294, ENST00000934295, ENST00000943453, ENST00000943454, ENST00000943455, ENST00000943456, ENST00000943457

RefSeq mRNA: 3 — MANE Select: NM_018719 NM_001127370, NM_001127371, NM_018719

CCDS: CCDS47558, CCDS47559, CCDS5374

Canonical transcript exons

ENST00000406877 — 10 exons

Exon	Start	End
ENSE00001086306	21911617	21911754
ENSE00001829726	21945781	21945899
ENSE00003492887	21906289	21906456
ENSE00003501747	21904110	21904259
ENSE00003513410	21906568	21906639
ENSE00003514664	21900899	21902352
ENSE00003563637	21905506	21905631
ENSE00003590286	21908130	21908507
ENSE00003590837	21902978	21903114
ENSE00003591023	21916754	21916894

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 97.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.8708 / max 203.1696, expressed in 1706 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83031	15.8708	1706

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	97.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.83	gold quality
ventricular zone	UBERON:0003053	96.67	gold quality
pancreatic ductal cell	CL:0002079	96.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.11	gold quality
right uterine tube	UBERON:0001302	95.72	gold quality
bone marrow	UBERON:0002371	93.91	gold quality
ganglionic eminence	UBERON:0004023	93.87	gold quality
palpebral conjunctiva	UBERON:0001812	93.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.05	gold quality
gingival epithelium	UBERON:0001949	92.72	gold quality
bone marrow cell	CL:0002092	92.39	gold quality
parietal pleura	UBERON:0002400	92.39	gold quality
epithelial cell of pancreas	CL:0000083	92.30	silver quality
parotid gland	UBERON:0001831	92.10	gold quality
left ventricle myocardium	UBERON:0006566	91.76	gold quality
endothelial cell	CL:0000115	91.51	gold quality
oviduct epithelium	UBERON:0004804	91.45	gold quality
gingiva	UBERON:0001828	90.18	gold quality
upper arm skin	UBERON:0004263	89.92	gold quality
trabecular bone tissue	UBERON:0002483	89.81	gold quality
body of pancreas	UBERON:0001150	89.42	gold quality
myocardium	UBERON:0002349	89.41	gold quality
body of stomach	UBERON:0001161	89.38	gold quality
right atrium auricular region	UBERON:0006631	89.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.36	gold quality
cardiac atrium	UBERON:0002081	89.30	gold quality
rectum	UBERON:0001052	89.25	gold quality
oocyte	CL:0000023	89.03	gold quality
secondary oocyte	CL:0000655	88.97	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	36.18
E-GEOD-134144	yes	26.62
E-GEOD-93593	yes	13.30
E-ANND-3	yes	10.40
E-MTAB-7303	no	72.59

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
MAOB	Repression

miRNA regulators (miRDB)

80 targeting CDCA7L, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-137-3P	99.87	74.74	2401

Literature-anchored findings (GeneRIF, showing 14)

• monoamine oxidase A activation of glucocorticoids and androgens is regulated differently by R1 and Sp1 (PMID:16728402)
• demonstrates the functions of MAO A and its repressor R1(RAM2/CDCA7L/JPO2) in apoptotic signaling pathways (PMID:16829576)
• Over-expression of JPO2 resulted in a modest but reproducible inhibition of HIV-1 replication, consistent with competition between integrase and JPO2 for binding to LEDGF/p75 (PMID:17669426)
• Reduction in R1 repressor protein correlates significantly with an increase (approximately 40%) in monoamine oxidase A protein levels within the major depressive disorder groups compared with controls. (PMID:21654740)
• CDCA7L was able to activate the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and regulate the cell cycle, thus promoting HCC progression. (PMID:24141559)
• Data indicate that JPO2 and LEDGF/p75 interact directly and specifically in vivo through the specific interaction domain of JPO2 and the C-terminal domain of LEDGF/p75. (PMID:24634210)
• The data are consistent with the rs4487645-CDCA7L loci being responsible for the chromosome 7p11.2 association with multiple myeloma risk, probably exerting its effects through an extended pathway involving IRF4 and MYC. (PMID:25480495)
• common LEDGF/p75 interaction interface shared by JPO2, PogZ, MLL1, IWS1 and HIV IN (PMID:26245978)
• We identify the Myc-interacting protein JPO2 and its partner binding protein LEDGF/p75 as critical modulators of PI3K/AKT signaling and metastasis in medulloblastoma (PMID:27013196)
• Suppression of CDCA7L limits multiple myeloma proliferation through apoptosis. (PMID:27882933)
• Study demonstrated the elevated expression of R1 in human prostate cancer tissue and cell lines at both protein and mRNA levels. Further results provide evidence that R1 is a novel regulator of prostate tumor growth by stabilizing c-Myc protein through transcriptional suppression of HUWE1. (PMID:30042175)
• CDCA7L is highly expressed in human glioma tissues and a high CDCA7L expression level predicts the dismal prognosis for glioma patients (PMID:30389317)
• Results identified and confirmed to have downregulated gene expression of SFRP5 in sporadic nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) and CDCA7L and RBM47 in MEN1-related NFPanNETs. (PMID:30620390)
• CDCA7L is highly expressed in human glioma tissues and that a high CDCA7L expression predicts a poor prognosis of glioma patients. CDCA7L promotes glioma U87 cell growth through CCND1. (PMID:31173217)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdca7b	ENSDARG00000076659
mus_musculus	Cdca7l	ENSMUSG00000021175
rattus_norvegicus	Cdca7l	ENSRNOG00000005410

Paralogs (1): CDCA7 (ENSG00000144354)

Protein

Protein identifiers

Cell division cycle-associated 7-like protein — Q96GN5 (reviewed: Q96GN5)

Alternative names: Protein JPO2, Transcription factor RAM2

All UniProt accessions (5): C9IZR6, C9J8L0, C9JFL7, Q96GN5, H7C1J6

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in transcriptional regulation as a repressor that inhibits monoamine oxidase A (MAOA) activity and gene expression by binding to the promoter. Plays an important oncogenic role in mediating the full transforming effect of MYC in medulloblastoma cells. Involved in apoptotic signaling pathways; May act downstream of P38-kinase and BCL-2, but upstream of CASP3/caspase-3 as well as CCND1/cyclin D1 and E2F1.

Subunit / interactions. Interacts with MYC. Interacts (via IBM motifs) with PSIP1 (via IBD domain); phosphorylation increases its affinity for PSIP1.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitous. Overexpressed in medulloblastoma.

Post-translational modifications. Phosphorylation increases its interaction with PSIP1.

Induction. By MYC overexpression in a concentration dependent manner in neuroblastoma cell line.

Miscellaneous. Cells lacking CDCA7L display a reduction of 25-30% of colony formation in medulloblastoma cell lines. CDCA7L overexpression induces colony formation.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96GN5-1	1, Variant C	yes
Q96GN5-2	2, Variant B
Q96GN5-4	3
Q96GN5-5	4

RefSeq proteins (3): NP_001120842, NP_001120843, NP_061189* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018866	Znf-4CXXC_R1	Domain
IPR040221	CDCA7/CDA7L	Family

Pfam: PF10497

UniProt features (42 total): modified residue 14, mutagenesis site 8, region of interest 3, splice variant 3, sequence conflict 3, helix 3, cross-link 2, sequence variant 2, short sequence motif 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5YI9	SOLUTION NMR
6EMO	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GN5-F1	66.23	0.29

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 (16): 81, 88, 105, 108, 117, 138, 139, 162, 195, 197, 261, 222, 225, 21, 77, 79

Mutagenesis-validated functional residues (8):

Position	Phenotype
16	significant loss of interaction with psip1; when associated with a-17. complete loss of interaction with psip1; when ass
17	significant loss of interaction with psip1; when associated with a-16. complete loss of interaction with psip1; when ass
21	phosphomimetic mutant. increased interaction with psip1; when associated with d-77, d-79 and d-81.
72	significant loss of interaction with psip1; when associated with a-73. complete loss of interaction with psip1; when ass
73	significant loss of interaction with psip1; when associated with a-72. complete loss of interaction with psip1; when ass
77	phosphomimetic mutant. increased interaction with psip1; when associated with d-21, d-79 and d-81.
79	phosphomimetic mutant. increased interaction with psip1; when associated with d-21, d-77 and d-81.
81	phosphomimetic mutant. increased interaction with psip1; when associated with d-21, d-77 and d-79.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 190 (showing top): GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, SHEPARD_BMYB_MORPHOLINO_DN, PAX2_01, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN, LIAO_METASTASIS, NKX25_01, FISCHER_DREAM_TARGETS, MODULE_397, MARKEY_RB1_ACUTE_LOF_UP, YAMAZAKI_TCEB3_TARGETS_DN, VERNELL_RETINOBLASTOMA_PATHWAY_UP, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, CUI_TCF21_TARGETS_2_UP, BERENJENO_TRANSFORMED_BY_RHOA_UP

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), positive regulation of cell population proliferation (GO:0008284)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
nuclear lumen	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
binding	1
nucleolus	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1062 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDCA7L	MYC	P01106	991
CDCA7L	PSIP1	O75475	848
CDCA7L	MAOA	P21397	738
CDCA7L	DBF4	Q9UBU7	605
CDCA7L	DPP4	P27487	575
CDCA7L	CDC7	O00311	548
CDCA7L	IWS1	Q96ST2	544
CDCA7L	E2F1	Q01094	510
CDCA7L	TOX4	O94842	496
CDCA7L	DNAH11	Q96DT5	491
CDCA7L	MEN1	O00255	480
CDCA7L	POGZ	Q7Z3K3	479
CDCA7L	ULK4	Q96C45	465
CDCA7L	HDGFL2	Q7Z4V5	447
CDCA7L	BCL2	P10415	446

IntAct

247 interactions, top by confidence:

A	B	Type	Score
CDCA7L	CEP70	psi-mi:“MI:0915”(physical association)	0.780
CEP70	CDCA7L	psi-mi:“MI:0915”(physical association)	0.780
EZH2	EPOP	psi-mi:“MI:0914”(association)	0.730
CDCA7L	MDFI	psi-mi:“MI:0915”(physical association)	0.720
CDCA7L	PRDM14	psi-mi:“MI:0915”(physical association)	0.720
ZGPAT	CDCA7L	psi-mi:“MI:0915”(physical association)	0.720
CDCA7L	CTNNBL1	psi-mi:“MI:0915”(physical association)	0.670
CARD9	CDCA7L	psi-mi:“MI:0915”(physical association)	0.670
CDCA7L	CARD9	psi-mi:“MI:0915”(physical association)	0.670
CTNNBL1	CDCA7L	psi-mi:“MI:0915”(physical association)	0.670
MLH1	CDCA7L	psi-mi:“MI:0915”(physical association)	0.670
CDCA7L	TRIM42	psi-mi:“MI:0915”(physical association)	0.560
PRPF31	CDCA7L	psi-mi:“MI:0915”(physical association)	0.560
UBL4A	CDCA7L	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (104): CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid), CDCA7L (Two-hybrid)

ESM2 similar proteins: A7E2Z2, A8WJ66, F7E540, G5E8P1, G5EEU2, O17514, O65312, O74508, O75164, P42124, P70351, Q08BS4, Q10077, Q14693, Q15910, Q18248, Q20318, Q24K09, Q28D84, Q28Z18, Q2NKX8, Q32KD2, Q4G059, Q4R381, Q4V863, Q504Y3, Q5RD88, Q5RDS6, Q61188, Q640I9, Q6ZT98, Q84WW6, Q8BRB7, Q8BZ21, Q8C0P7, Q8VCD7, Q8W595, Q8WML3, Q8WYB5, Q92794

Diamond homologs: C0SUU8, C0SV12, F4HZD1, O43593, P97609, Q32PH1, Q4G059, Q4KM91, Q61645, Q8VYB9, Q922M5, Q96GN5, Q9BWT1, Q9D0M2, Q9SSE9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDCA7L	“down-regulates quantity by repression”	MAOB	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 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.

GO biological processes:

GO term	Partners	Fold	FDR
chromatin remodeling	8	9.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	33
Likely pathogenic	7
Uncertain significance	111
Likely benign	57
Benign	4

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1403283	NM_001277115.2(DNAH11):c.13451_13452dup (p.Leu4485fs)	Pathogenic
1451503	NM_001277115.2(DNAH11):c.13364_13415dup (p.Lys4473fs)	Pathogenic
1457437	NM_001277115.2(DNAH11):c.13480_13492dup (p.Ser4498fs)	Pathogenic
1944204	NM_001277115.2(DNAH11):c.13320_13350dup (p.Lys4451delinsProSerArgAsnHisCysTer)	Pathogenic
238901	NM_001277115.2(DNAH11):c.13501_13502insGGACTGCAAAATGGGTTCTGGCTGGAGTGGCTCTGCTTCTAGAAGCGTAAGGTAACACTGGCATTCCTCTAGCCTCTGCTGGAGTGCAGTGAGGATTTTCTAGCATGTTGCTGCACTGTTCCCATTCTGGACCTTCAGGCTGAAGAGCGAAGAGA (p.Lys4501delinsArgThrAlaLysTrpValLeuAlaGlyValAlaLeuLeuLeuGluAlaTer)	Pathogenic
2424085	NC_000007.13:g.(?20994491)(23030730_?)del	Pathogenic
2697453	NM_001277115.2(DNAH11):c.13406_13409del (p.Arg4469fs)	Pathogenic
2724033	NM_001277115.2(DNAH11):c.13420C>T (p.Gln4474Ter)	Pathogenic
2733656	NM_001277115.2(DNAH11):c.13416_13449dup (p.Lys4484delinsGlnThrAspLeuArgValProCysValTer)	Pathogenic
2758563	NM_001277115.2(DNAH11):c.13409_13424del (p.Gln4470fs)	Pathogenic
2759706	NM_001277115.2(DNAH11):c.13439_13449dup (p.Lys4484fs)	Pathogenic
2781394	NM_001277115.2(DNAH11):c.13476dup (p.Thr4493fs)	Pathogenic
2784625	NM_001277115.2(DNAH11):c.13411_13423del (p.Glu4471fs)	Pathogenic
2806095	NM_001277115.2(DNAH11):c.13396_13426dup (p.Tyr4476fs)	Pathogenic
2838485	NM_001277115.2(DNAH11):c.13416_13428del (p.Lys4473fs)	Pathogenic
2840690	NM_001277115.2(DNAH11):c.13416del (p.Lys4473fs)	Pathogenic
2890820	NM_001277115.2(DNAH11):c.13313G>A (p.Trp4438Ter)	Pathogenic
2893769	NM_001277115.2(DNAH11):c.13480_13489dup (p.Lys4497fs)	Pathogenic
2919234	NM_001277115.2(DNAH11):c.13380_13383dup (p.Ala4462fs)	Pathogenic
3650405	NM_001277115.2(DNAH11):c.13380_13387dup (p.Lys4463fs)	Pathogenic
3678147	NM_001277115.2(DNAH11):c.13484_13496dup (p.Glu4500fs)	Pathogenic
3705389	NM_001277115.2(DNAH11):c.13411_13418del (p.Glu4471fs)	Pathogenic
4075901	GRCh37/hg19 7p15.3(chr7:21925654-21962110)x1	Pathogenic
454658	NM_001277115.2(DNAH11):c.13321C>T (p.Gln4441Ter)	Pathogenic
454661	NM_001277115.2(DNAH11):c.13494_13500del (p.Ser4498fs)	Pathogenic
4713371	NM_001277115.2(DNAH11):c.13494_13500dup (p.Lys4501fs)	Pathogenic
4723553	NM_001277115.2(DNAH11):c.13495G>T (p.Glu4499Ter)	Pathogenic
4736310	NM_001277115.2(DNAH11):c.13422_13450dup (p.Lys4484fs)	Pathogenic
4739848	NM_001277115.2(DNAH11):c.13390_13415dup (p.Lys4473fs)	Pathogenic
4741926	NM_001277115.2(DNAH11):c.13386_13399dup (p.Val4467fs)	Pathogenic

SpliceAI

2384 predictions. Top by Δscore:

Variant	Effect	Δscore
7:21899976:A:AG	acceptor_gain	1.0000
7:21899977:A:G	acceptor_gain	1.0000
7:21899979:GCA:G	acceptor_gain	1.0000
7:21899979:GCAAT:G	acceptor_gain	1.0000
7:21900116:GGAGG:G	donor_gain	1.0000
7:21900117:GAGGG:G	donor_gain	1.0000
7:21900119:GG:G	donor_gain	1.0000
7:21900120:GG:G	donor_gain	1.0000
7:21901002:CATAG:C	acceptor_loss	1.0000
7:21901005:A:AC	acceptor_loss	1.0000
7:21901005:A:AG	acceptor_gain	1.0000
7:21901006:G:A	acceptor_loss	1.0000
7:21901006:G:GG	acceptor_gain	1.0000
7:21901006:GGC:G	acceptor_gain	1.0000
7:21904104:TCCTA:T	donor_loss	1.0000
7:21904105:CCTA:C	donor_loss	1.0000
7:21904106:CTAC:C	donor_loss	1.0000
7:21904107:TAC:T	donor_loss	1.0000
7:21904108:A:AC	donor_gain	1.0000
7:21904108:A:AG	donor_loss	1.0000
7:21904109:C:CC	donor_gain	1.0000
7:21904109:C:T	donor_loss	1.0000
7:21904135:T:TA	donor_gain	1.0000
7:21904255:TTACC:T	acceptor_gain	1.0000
7:21904256:TACC:T	acceptor_gain	1.0000
7:21904258:CC:C	acceptor_gain	1.0000
7:21904259:CC:C	acceptor_gain	1.0000
7:21904260:C:CC	acceptor_gain	1.0000
7:21904260:CT:C	acceptor_loss	1.0000
7:21905499:A:AC	donor_gain	1.0000

AlphaMissense

3000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:21903020:G:T	A431D	1.000
7:21903109:C:A	W401C	1.000
7:21903109:C:G	W401C	1.000
7:21904147:C:G	R387P	1.000
7:21904148:G:T	R387S	1.000
7:21904158:G:C	C383W	1.000
7:21904160:A:G	C383R	1.000
7:21904169:A:G	C380R	1.000
7:21904170:G:C	F379L	1.000
7:21904170:G:T	F379L	1.000
7:21904171:A:G	F379S	1.000
7:21904172:A:G	F379L	1.000
7:21904240:C:G	C356S	1.000
7:21904241:A:G	C356R	1.000
7:21904241:A:T	C356S	1.000
7:21904247:G:C	H354D	1.000
7:21904248:G:C	C353W	1.000
7:21904250:A:G	C353R	1.000
7:21902988:A:C	Y442D	0.999
7:21903032:A:G	L427P	0.999
7:21903038:C:T	G425E	0.999
7:21903065:C:G	R416P	0.999
7:21903068:C:G	C415S	0.999
7:21903069:A:G	C415R	0.999
7:21903069:A:T	C415S	0.999
7:21903076:G:C	C412W	0.999
7:21903077:C:A	C412F	0.999
7:21903077:C:T	C412Y	0.999
7:21903078:A:G	C412R	0.999
7:21903079:A:C	N411K	0.999

dbSNP variants (sampled 300 via entrez): RS1000030146 (7:21902469 A>C,G), RS1000107695 (7:21905731 A>AC), RS1000223498 (7:21924495 G>A,C), RS1000236351 (7:21942506 G>T), RS1000269727 (7:21934589 TTTAAATGTG>T), RS1000287002 (7:21918863 A>C), RS1000499152 (7:21922426 G>C), RS1000651402 (7:21913829 A>G), RS1000687657 (7:21909592 T>A,C), RS1000722797 (7:21904964 G>C), RS1000726540 (7:21936966 A>C), RS1000751519 (7:21911375 A>G), RS1000810978 (7:21939338 A>C), RS1000837154 (7:21901553 A>AACAAG), RS1000847582 (7:21924816 C>T)

Disease associations

OMIM: gene MIM:609685 | disease phenotypes: MIM:244400, MIM:611884, MIM:610532

GenCC curated gene-disease

Mondo (4): primary ciliary dyskinesia (MONDO:0016575), primary ciliary dyskinesia 7 (MONDO:0012748), situs inversus (MONDO:0010029), hypomyelinating leukodystrophy 5 (MONDO:0012514)

Orphanet (3): Primary ciliary dyskinesia (Orphanet:244), Situs inversus totalis (Orphanet:101063), Hypomyelination-congenital cataract syndrome (Orphanet:85163)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001696	Situs inversus totalis

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000611_12	Height	5.000000e-06
GCST002828_15	Urate levels in obese individuals	4.000000e-06
GCST002921_6	Multiple myeloma	4.000000e-08
GCST002922_7	Multiple myeloma and monoclonal gammopathy	2.000000e-08
GCST004750_17	Squamous cell lung carcinoma	5.000000e-06
GCST004988_679	Breast cancer	2.000000e-08
GCST008758_39	Pre-treatment viral load in HIV-1 infection	4.000000e-18
GCST011349_6	Gamma glutamyl transferase levels	4.000000e-09
GCST012396_8	Multiple myeloma	5.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0010125	viral load
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480
D012857	Situs Inversus	C16.131.810
C567504	Ciliary Dyskinesia, Primary, 7 (supp.)
C567166	Leukodystrophy, Hypomyelinating, 5 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Tretinoin	decreases expression	4
trichostatin A	affects cotreatment, increases expression	3
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	3
Aflatoxin B1	affects expression, increases expression, increases methylation	3
bisphenol A	decreases methylation, increases expression	2
sodium arsenite	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	decreases reaction, increases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
NSC 689534	decreases expression, affects binding	1
Resveratrol	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02871778	PHASE2	COMPLETED	Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
NCT07318974	PHASE2	ACTIVE_NOT_RECRUITING	Melatonin Therapy for Improving ICSI Outcomes in Women With Diminished Ovarian Reserve
NCT05737485	PHASE1	COMPLETED	Study Evaluating the Safety and Tolerability of RCT1100 in Healthy and PCD Subjects
NCT06600425	PHASE1	COMPLETED	A Study to Assess the Safety, Tolerability, Ciliary Rescue, and Pharmacodynamics of RCT1100 in Adults With PCD
NCT06633757	PHASE1	COMPLETED	Study of Inhaled RCT1100 in Adults With PCD Caused by Pathogenic Mutations in the DNAI1 Gene to Measure Mucociliary Clearance
NCT04901715	EARLY_PHASE1	COMPLETED	Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
NCT00005650	Not specified	COMPLETED	Genetic Study of Patients With Primary Ciliary Dyskinesia
NCT00323167	Not specified	COMPLETED	Rare Genetic Disorders of the Breathing Airways
NCT00368446	Not specified	COMPLETED	Genetic Disorders of Mucociliary Clearance in Nontuberculous Mycobacterial Lung Disease
NCT00450918	Not specified	COMPLETED	Evaluating Progression of and Diagnostic Tools for Primary Ciliary Dyskinesia in Children and Adolescents
NCT00608556	Not specified	COMPLETED	Dyskinesia, Heterotaxy and Congenital Heart Disease
NCT00686309	Not specified	UNKNOWN	Comparison of On-line and Off-line Measurements of Exhaled Nitric Oxide (NO)
NCT00722878	Not specified	COMPLETED	Long-term Lung Function and Disease Progression in Children With Early Onset Primary Ciliary Dyskinesia Lung Disease
NCT00739817	Not specified	UNKNOWN	Screening for Primary Ciliary Dyskinesia Using Nasal Nitric Oxide
NCT00783887	Not specified	COMPLETED	Diagnosis of Primary Ciliary Dyskinesia
NCT00807482	Not specified	RECRUITING	Pathogenesis of Primary Ciliary Dyskinesia (PCD) Lung Disease
NCT01070914	Not specified	UNKNOWN	Early Detection and Characterization of Primary Ciliary Dyskinesia
NCT01155115	Not specified	COMPLETED	Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
NCT01246258	Not specified	COMPLETED	Otolith Function in Patients With Primary Ciliary Dyskinesia
NCT01929356	Not specified	RECRUITING	Chest Physiotherapy and Lung Function in Primary Ciliary Dyskinesia
NCT02389049	Not specified	COMPLETED	Genetics of Primary Ciliary Dyskinesia
NCT02419365	Not specified	RECRUITING	International Primary Ciliary Dyskinesia (PCD) Registry
NCT02699177	Not specified	UNKNOWN	In Vivo Measurements of Nasal Ciliary Beat Frequency by Using Interferometry
NCT02704455	Not specified	NOT_YET_RECRUITING	Registry Study on Primary Ciliary Dyskinesia in Chinese Children
NCT03271840	Not specified	COMPLETED	Registry for Primary Ciliary Dyskinesia
NCT03279965	Not specified	UNKNOWN	MRI in Cystic Fibrosis and Primary Ciliary Dyskinesia
NCT03320382	Not specified	UNKNOWN	Multiple Breath Washout, a Clinimetric Dataset
NCT03370029	Not specified	COMPLETED	Respiratory Muscle Strength, Exercise Capacity and Physical Activity Levels in Children Primary Ciliary Dyskinesia
NCT03494894	Not specified	COMPLETED	Bacteriological Link Between Upper and Lower Airways in Cystic Fibrosis and Primary Ciliary Dyskinesia
NCT03517865	Not specified	ACTIVE_NOT_RECRUITING	International Primary Ciliary Dyskinesia Cohort
NCT03606200	Not specified	RECRUITING	Swiss Primary Ciliary Dyskinesia Registry
NCT03704207	Not specified	RECRUITING	Utility of PCD Diagnostics to Improve Clinical Care
NCT03704896	Not specified	UNKNOWN	PRospective Observational Multicentre Study on VAriability of Lung Function in Stable PCD Patients
NCT03801395	Not specified	COMPLETED	PCD New Gene Discovery
NCT03809091	Not specified	UNKNOWN	WGS of Korean Idiopathic Bronchiectasis
NCT03832491	Not specified	COMPLETED	Effect of Game Based Approach on Oxygenation, Functional Capacity and Quality of Life in Primary Ciliary Dyskinesia
NCT04161313	Not specified	COMPLETED	Respiratory Function, Exercise Capacity and Peripheral Muscle Strength Among Patients With CF, PCD and Healthy Children
NCT04476433	Not specified	COMPLETED	Intervention in Chronic Pediatric Patients and Their Families.
NCT04489472	Not specified	UNKNOWN	The Effect of a Dietary Supplement Rich in Nitric Oxide in Patients Diagnosed With Primary Ciliary Dyskinesia.
NCT04602481	Not specified	RECRUITING	Living With Primary Ciliary Dyskinesia (Living With PCD)