CDCA7

Summary

CDCA7 (cell division cycle associated 7, HGNC:14628) is a protein-coding gene on chromosome 2q31.1, encoding Cell division cycle-associated protein 7 (Q9BWT1). Participates in MYC-mediated cell transformation and apoptosis; induces anchorage-independent growth and clonogenicity in lymphoblastoid cells.

This gene was identified as a c-Myc responsive gene, and behaves as a direct c-Myc target gene. Overexpression of this gene is found to enhance the transformation of lymphoblastoid cells, and it complements a transformation-defective Myc Box II mutant, suggesting its involvement in c-Myc-mediated cell transformation. Two alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 83879 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency-centromeric instability-facial anomalies syndrome 3 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 19
• Clinical variants (ClinVar): 292 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 39
• MANE Select transcript: NM_031942

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14628
Approved symbol	CDCA7
Name	cell division cycle associated 7
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14736, JPO1
Ensembl gene	ENSG00000144354
Ensembl biotype	protein_coding
OMIM	609937
Entrez	83879

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 16 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000306721, ENST00000347703, ENST00000410019, ENST00000410101, ENST00000435616, ENST00000467411, ENST00000468359, ENST00000496441, ENST00000695901, ENST00000695911, ENST00000695912, ENST00000695913, ENST00000695914, ENST00000695918, ENST00000858243, ENST00000858244, ENST00000911358, ENST00000911359, ENST00000911360, ENST00000911361, ENST00000911362, ENST00000911363, ENST00000911364

RefSeq mRNA: 2 — MANE Select: NM_031942 NM_031942, NM_145810

CCDS: CCDS2252, CCDS2253

Canonical transcript exons

ENST00000306721 — 10 exons

Exon	Start	End
ENSE00003461910	173365452	173365592
ENSE00003588034	173363818	173363895
ENSE00003592214	173363226	173363462
ENSE00003615004	173367150	173367286
ENSE00003680279	173364795	173364989
ENSE00003965446	173367634	173368997
ENSE00003965449	173354872	173354984
ENSE00003965450	173366283	173366432
ENSE00003965461	173358712	173358837
ENSE00003965463	173359255	173359491

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 98.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.0535 / max 441.0660, expressed in 1464 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23772	26.0535	1464

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	98.48	gold quality
ventricular zone	UBERON:0003053	97.97	gold quality
embryo	UBERON:0000922	96.71	gold quality
ganglionic eminence	UBERON:0004023	96.71	gold quality
thymus	UBERON:0002370	95.42	gold quality
rectum	UBERON:0001052	93.31	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.66	gold quality
duodenum	UBERON:0002114	92.15	gold quality
colonic mucosa	UBERON:0000317	92.14	gold quality
jejunal mucosa	UBERON:0000399	90.62	gold quality
pylorus	UBERON:0001166	89.37	gold quality
endometrium	UBERON:0001295	89.35	gold quality
mucosa of transverse colon	UBERON:0004991	88.95	gold quality
upper arm skin	UBERON:0004263	88.33	gold quality
epithelial cell of pancreas	CL:0000083	87.27	gold quality
upper leg skin	UBERON:0004262	86.45	gold quality
pancreatic ductal cell	CL:0002079	86.29	gold quality
bone marrow	UBERON:0002371	86.21	gold quality
caecum	UBERON:0001153	85.70	gold quality
vermiform appendix	UBERON:0001154	85.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.13	gold quality
epithelium of nasopharynx	UBERON:0001951	85.07	gold quality
esophagus squamous epithelium	UBERON:0006920	84.25	gold quality
lymph node	UBERON:0000029	83.81	gold quality
oral cavity	UBERON:0000167	83.35	gold quality
esophagus mucosa	UBERON:0002469	82.45	gold quality
placenta	UBERON:0001987	81.98	gold quality
small intestine	UBERON:0002108	81.76	gold quality
skin of hip	UBERON:0001554	81.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	201.86
E-MTAB-6108	yes	121.88
E-CURD-112	yes	42.76
E-HCAD-6	yes	28.76
E-ANND-3	yes	10.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F2, E2F3, E2F4, MYC

miRNA regulators (miRDB)

99 targeting CDCA7, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-106B-5P	99.88	74.72	2795

Literature-anchored findings (GeneRIF, showing 23)

• JPO1/CDCA7 is a unique transcription regulator whose expression is activated by E2F1 as well as c-Myc. (PMID:16580749)
• CDCA7 associates with MYC and this association is modulated in a phosphorylation-dependent manner. (PMID:23166294)
• The CDCA7 transcription factor regulates cell proliferation. (PMID:24029427)
• Data indicate that cell division cycle associated 7 protein (Cdca7) is strongly up-regulated in the hemogenic population during embryonic stem cell hematopoietic differentiation in a Notch-dependent manner. (PMID:25385755)
• Missense mutations in CDCA7 cause immunodeficiency-centromeric instability-facial anomalies syndrome type 3. (PMID:26216346)
• Transcriptome analysis identified Cdca7 as the top down-regulated gene in Zbtb24 homozygous mutant mESCs, which can be restored by ectopic ZBTB24 expression. Finally, we show that this regulation is conserved between species and that CDCA7 levels are reduced in patients carrying ZBTB24 nonsense mutations (PMID:27466202)
• HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex; immunodeficiency-centromeric instability-facial anomalies syndrome has a defective HELLS and CDCA7 bipartite nucleosome remodeling complex (PMID:29339483)
• Here, we performed a comparative analysis of perturbed DNA methylation landscapes in a cohort of ICF patients using an array-based assay to (i) evaluate the similarities and differences in methylation landscapes depending on patient genotypes as an index of a functional link between the four ICF factors, (ii) identify genomic regions that rely on DNMT3B, ZBTB24, CDCA7 or HELLS for their methylation status (PMID:29659838)
• CDCA7 was not required for anchorage-dependent growth of normal fibroblasts or non-malignant lymphocytes, it was essential but not sufficient for anchorage-independent growth of lymphoid tumor cells and for lymphomagenesis. (PMID:29880607)
• in contrast to Immunodeficiency, Centromeric instability and Facial anomalies syndrome type 1 (ICF1), the subtelomeric methylation patterns in cells of ICF2-4 patients do not differ significantly from those in normal cells, and ICF2-4 cells exhibit a normal telomeric phenotype. Also knocking down the expression of ZBTB24, CDCA7 and HELLS in normal human fibroblasts does not affect subtelomeric methylation. (PMID:30010917)
• Immunohistochemical analysis revealed that the CDCA7/EZH2 axis was clinical relevant. These findings suggest CDCA7 plays a crucial role in TNBC progression by transcriptionally upregulating EZH2. (PMID:30151890)
• the C-NHEJ defect alone did not cause CG hypomethylation, CDCA7 and HELLS are involved in maintaining CG methylation at centromeric and pericentromeric repeats. The defect in C-NHEJ may account for some common features of immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome cells, including centromeric instability, abnormal chromosome segregation, and apoptosis. (PMID:30307408)
• ZBTB24 activates the expression of CDCA7 in T cells. (PMID:31030944)
• The inhibiting effects of FGD5-AS1 knockdown on colorectal cancer (CRC) cell proliferation, migration, and invasion, and the promoting effects on CRC cell apoptosis could be revived by miR-302e suppression or CDCA7 upregulation. (PMID:31332696)
• the CDCA7 gene may play a tumor-promoting role in lung adenocarcinoma (PMID:31570276)
• High expression of CDCA7 predicts tumor progression and poor prognosis in human colorectal cancer. (PMID:32319649)
• CDCA7 and HELLS suppress DNA:RNA hybrid-associated DNA damage at pericentromeric repeats. (PMID:33082427)
• CDCA7-regulated inflammatory mechanism through TLR4/NF-kappaB signaling pathway in stomach adenocarcinoma. (PMID:34339079)
• Downregulation of cell division cycle-associated protein 7 (CDCA7) suppresses cell proliferation, arrests cell cycle of ovarian cancer, and restrains angiogenesis by modulating enhancer of zeste homolog 2 (EZH2) expression. (PMID:34551671)
• CDCA7 promotes TGF-beta-induced epithelial-mesenchymal transition via transcriptionally regulating Smad4/Smad7 in ESCC. (PMID:36056599)
• High Expression of CDCA7 in the Prognosis of Glioma and Its Relationship with Ferroptosis and Immunity. (PMID:37510310)
• Circ_0006220 (circ-TADA2A) accelerates prostate cancer cell malignant behaviors through miR-520f-3p/CDCA7 axis. (PMID:39097891)
• The ICF syndrome protein CDCA7 harbors a unique DNA binding domain that recognizes a CpG dyad in the context of a non-B DNA. (PMID:39178265)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdca7a	ENSDARG00000077620
mus_musculus	Cdca7	ENSMUSG00000055612
rattus_norvegicus	Cdca7	ENSRNOG00000001514

Paralogs (1): CDCA7L (ENSG00000164649)

Protein

Protein identifiers

Cell division cycle-associated protein 7 — Q9BWT1 (reviewed: Q9BWT1)

Alternative names: Protein JPO1

All UniProt accessions (6): Q9BWT1, A0A8Q3SIB2, A0A8Q3WKV4, A0A8Q3WLW5, A0A8Q3WM52, F8WBA7

UniProt curated annotations — full annotation on UniProt →

Function. Participates in MYC-mediated cell transformation and apoptosis; induces anchorage-independent growth and clonogenicity in lymphoblastoid cells. Insufficient to induce tumorigenicity when overexpressed but contributes to MYC-mediated tumorigenesis. Also functions as a critical cofactor for the chromatin remodeler HELLS, facilitating its recruitment to specific genomic regions to maintain DNA methylation patterns and heterochromatin integrity. Recognizes hemimethylated CpG within nucleosomes where it recruits HELLS to remodel chromatin and facilitate access of de novo DNA methyltransferases to heterochromatic regions, enabling proper establishment of DNA methylation patterns. May play a role as transcriptional regulator.

Subunit / interactions. Interacts with MYC (via C-terminus), YWHAE and YWHAZ. Interacts with HELLS; the interaction brings HELLS to chromatin and recruits DNA methyltransferases to heterochromatin regions.

Subcellular location. Nucleus. Cytoplasm. Chromosome.

Tissue specificity. Ubiquitous with higher level in thymus and small intestine. Overexpressed in a large number of tumors, in blood from patients with acute myelogenous leukemia (AML) and in chronic myelogenous leukemia (CML) blast crisis.

Post-translational modifications. Phosphorylation at Thr-163 promotes interaction with YWHAE and YWHAZ, dissociation from MYC and sequestration in the cytoplasm. In vitro, phosphorylated at Thr-163 by AKT.

Disease relevance. Immunodeficiency-centromeric instability-facial anomalies syndrome 3 (ICF3) [MIM:616910] A rare disorder characterized by a variable immunodeficiency resulting in recurrent infections, facial anomalies, and branching of chromosomes 1, 9, and 16. Other variable symptoms include growth retardation, failure to thrive, and psychomotor retardation. Laboratory studies show limited hypomethylation of DNA in a small fraction of the genome in some, but not all, patients. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. Hemimethylation-sensing zinc finger (HMZF) domain recognizes hemimethylated CpG in the outward-facing DNA major groove within the nucleosome core particle. CDCA7-HELLS nucleosome remodeling complex assists the maintenance of DNA methylation on chromatin by sensing hemimethylated CpG through HMZF.

Induction. Activated by MYC and possibly E2F1.

Miscellaneous. CDCA7 expression is correlated with MYC expression in lymphoblastoid, lymphoma and breast cancer cell lines.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9BWT1-1	1, isoform 2 variant	yes
Q9BWT1-2	2
Q9BWT1-3	3
Q9BWT1-4	4
Q9BWT1-5	5
Q9BWT1-6	6

RefSeq proteins (2): NP_114148, NP_665809 (=MANE)

Domains & families (InterPro)

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

Pfam: PF10497

UniProt features (52 total): mutagenesis site 15, helix 7, splice variant 6, turn 5, sequence variant 4, region of interest 3, sequence conflict 3, modified residue 3, chain 1, zinc finger region 1, cross-link 1, strand 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8TLK	X-RAY DIFFRACTION	2.99
8YV8	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWT1-F1	68.93	0.33

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 (4): 204, 142, 163, 190

Mutagenesis-validated functional residues (15):

Position	Phenotype
158	does not affect phosphorylation or interaction with yhwae and yhwaz.
159	does not affect phosphorylation or interaction with yhwae and yhwaz.
160	abolishes phosphorylation and interaction with yhwae and yhwaz.
160	predominantly cytoplasmic.
161	increased phosphorylation, binding to yhwae and yhwaz, and cytoplasmic expression.
161	predominantly cytoplasmic.
162	does not affect phosphorylation or interaction with yhwae and yhwaz.
162	predominantly cytoplasmic.
163	abolishes phosphorylation, interaction with yhwae and yhwaz, and cytoplasmic localization.
164	abolishes phosphorylation and interaction with yhwae and yhwaz.
165	abolishes phosphorylation, interaction with yhwae and yhwaz, and cytoplasmic localization.
171	predominantly cytoplasmic. completely cytoplasmic with no nuclear expression; when associated with e-176.
176	predominantly cytoplasmic. completely cytoplasmic with no nuclear expression; when associated with e-171.
182	no effect on subcellular location.
184	no effect on subcellular location.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 300 (showing top): E2F_Q4, E2F_Q4_01, TAATAAT_MIR126, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, E2F4DP1_01, FISCHER_G1_S_CELL_CYCLE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, CAIRO_PML_TARGETS_BOUND_BY_MYC_UP, KYNG_DNA_DAMAGE_DN, PATIL_LIVER_CANCER, E2F1DP1_01, E2F_Q3, E2F1DP2_01, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN

GO Biological Process (3): regulation of DNA-templated transcription (GO:0006355), apoptotic process (GO:0006915), regulation of cell population proliferation (GO:0042127)

GO Molecular Function (2): hemi-methylated DNA-binding (GO:0044729), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell population proliferation	1
regulation of cellular process	1
double-stranded DNA binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1847 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDCA7	HELLS	Q9NRZ9	783
CDCA7	ZBTB24	O43167	724
CDCA7	CDCA2	Q69YH5	598
CDCA7	MYC	P01106	553
CDCA7	CDCA4	Q9BXL8	545
CDCA7	CDCA3	Q99618	532
CDCA7	ATAD2	Q6PL18	529
CDCA7	CDCA8	Q53HL2	510
CDCA7	CDCA5	Q96FF9	506
CDCA7	AURKB	Q96GD4	501
CDCA7	SP3	Q02447	495
CDCA7	KIF4A	O95239	449
CDCA7	NUF2	Q9BZD4	445
CDCA7	KIF20A	O95235	444
CDCA7	KIF14	Q15058	443

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CDCA7	WFS1	psi-mi:“MI:0915”(physical association)	0.560
HTT	CDCA7	psi-mi:“MI:0915”(physical association)	0.560
PARP2	CDCA7	psi-mi:“MI:0557”(adp ribosylation reaction)	0.440
CDCA7	YWHAG	psi-mi:“MI:0914”(association)	0.350
CDCA7	CD33	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): YWHAQ (Affinity Capture-MS), SFN (Affinity Capture-MS), YWHAZ (Affinity Capture-MS), YWHAH (Affinity Capture-MS), CDCA7 (Reconstituted Complex), YWHAZ (Affinity Capture-MS), YWHAG (Affinity Capture-MS), YWHAH (Affinity Capture-MS), CDCA7 (Affinity Capture-RNA), YWHAZ (Affinity Capture-MS), YWHAG (Affinity Capture-MS), CDCA7 (Proximity Label-MS), CDCA7 (Protein-peptide), CDCA7 (Proximity Label-MS), CDCA7 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0G2L7I0, A2VDP0, A2YX04, A5D979, B4FM28, B6SLJ0, D3ZVU1, F4I8S3, F4KFC7, F6UH96, G3X912, O01835, Q0J9J6, Q22557, Q24595, Q2HJG4, Q32LR5, Q38796, Q4KM91, Q53WJ1, Q5U3H2, Q65Z40, Q680Q4, Q6E3D5, Q6PI47, Q6Z8M8, Q700C2, Q7KW09, Q7XC57, Q7Y1C4, Q7Y1C5, Q7Z5K2, Q7ZXG4, Q801E2, Q8L840, Q8RY95, Q91W18, Q91ZX6, Q941B6, Q9BVC5

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

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AKT	down-regulates	CDCA7	phosphorylation
AKT1	down-regulates	CDCA7	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	120
Likely benign	138
Benign	14

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3247568	NC_000002.11:g.(?173420879)(174232392_?)del	Pathogenic
1879493	NM_031942.5(CDCA7):c.1223G>A (p.Cys408Tyr)	Likely pathogenic
225529	NM_031942.5(CDCA7):c.1057C>T (p.Arg353Cys)	Likely pathogenic
225532	NM_031942.5(CDCA7):c.1058G>A (p.Arg353His)	Likely pathogenic

SpliceAI

1627 predictions. Top by Δscore:

Variant	Effect	Δscore
2:173358707:TGCA:T	acceptor_loss	1.0000
2:173358709:CA:C	acceptor_loss	1.0000
2:173358710:A:AG	acceptor_gain	1.0000
2:173358710:A:C	acceptor_loss	1.0000
2:173358711:G:GA	acceptor_gain	1.0000
2:173358711:GC:G	acceptor_gain	1.0000
2:173358711:GCA:G	acceptor_gain	1.0000
2:173358711:GCAG:G	acceptor_loss	1.0000
2:173358711:GCAGA:G	acceptor_gain	1.0000
2:173358833:ACACG:A	donor_gain	1.0000
2:173358834:CACG:C	donor_gain	1.0000
2:173358835:ACG:A	donor_gain	1.0000
2:173358836:CG:C	donor_gain	1.0000
2:173358837:GG:G	donor_gain	1.0000
2:173358838:G:GA	donor_loss	1.0000
2:173358838:G:GG	donor_gain	1.0000
2:173358839:T:TC	donor_loss	1.0000
2:173363814:TTA:T	acceptor_loss	1.0000
2:173363815:TA:T	acceptor_loss	1.0000
2:173363816:A:AC	acceptor_loss	1.0000
2:173363816:A:AG	acceptor_gain	1.0000
2:173363816:AGCTT:A	acceptor_gain	1.0000
2:173363817:G:GA	acceptor_gain	1.0000
2:173363817:GC:G	acceptor_gain	1.0000
2:173363817:GCT:G	acceptor_gain	1.0000
2:173363817:GCTT:G	acceptor_gain	1.0000
2:173363817:GCTTG:G	acceptor_gain	1.0000
2:173363896:G:GG	donor_gain	1.0000
2:173364939:GA:G	donor_gain	1.0000
2:173364965:G:GT	donor_gain	1.0000

AlphaMissense

2971 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:173366292:T:C	C270R	1.000
2:173366293:G:A	C270Y	1.000
2:173366294:T:G	C270W	1.000
2:173366295:C:G	H271D	1.000
2:173366297:T:A	H271Q	1.000
2:173366297:T:G	H271Q	1.000
2:173366301:T:A	C273S	1.000
2:173366301:T:C	C273R	1.000
2:173366302:G:C	C273S	1.000
2:173366304:C:A	R274S	1.000
2:173366309:G:C	Q275H	1.000
2:173366309:G:T	Q275H	1.000
2:173366327:A:C	K281N	1.000
2:173366327:A:T	K281N	1.000
2:173366334:T:C	C284R	1.000
2:173366371:T:C	F296S	1.000
2:173366373:T:C	C297R	1.000
2:173366374:G:A	C297Y	1.000
2:173367153:T:A	W318R	1.000
2:173367153:T:C	W318R	1.000
2:173367155:G:C	W318C	1.000
2:173367155:G:T	W318C	1.000
2:173367159:T:C	C320R	1.000
2:173366283:G:C	G267R	0.999
2:173366292:T:A	C270S	0.999
2:173366293:G:C	C270S	0.999
2:173366293:G:T	C270F	0.999
2:173366295:C:A	H271N	0.999
2:173366302:G:A	C273Y	0.999
2:173366302:G:T	C273F	0.999

dbSNP variants (sampled 300 via entrez): RS1000052818 (2:173369475 G>A), RS1000058635 (2:173364467 C>G), RS1000104786 (2:173369200 C>G), RS1000128877 (2:173364985 T>C), RS1000180300 (2:173356061 A>G), RS1000424376 (2:173355863 G>T), RS1000454945 (2:173368437 T>C,G), RS1001144763 (2:173356657 G>A,C), RS1001184351 (2:173361848 C>T), RS1001566708 (2:173361524 T>G), RS1001603117 (2:173355476 C>A,G,T), RS1001664441 (2:173369133 C>T), RS1001675082 (2:173367992 G>A), RS1002034182 (2:173355292 G>T), RS1002388295 (2:173355857 G>A)

Disease associations

OMIM: gene MIM:609937 | disease phenotypes: MIM:616910

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency-centromeric instability-facial anomalies syndrome 3	Strong	Autosomal recessive
immunodeficiency-centromeric instability-facial anomalies syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
immunodeficiency-centromeric instability-facial anomalies syndrome 3	Moderate	AR

Mondo (2): immunodeficiency-centromeric instability-facial anomalies syndrome 3 (MONDO:0014828), immunodeficiency-centromeric instability-facial anomalies syndrome (MONDO:0000133)

Orphanet (1): ICF syndrome (Orphanet:2268)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000158	Macroglossia
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000486	Strabismus
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001334	Communicating hydrocephalus
HP:0001511	Intrauterine growth retardation
HP:0001537	Umbilical hernia
HP:0001874	Abnormality of neutrophils
HP:0001888	Decreased total lymphocyte count
HP:0001903	Anemia
HP:0002024	Malabsorption
HP:0002205	Recurrent respiratory infections
HP:0002719	Recurrent infections
HP:0002721	Immunodeficiency
HP:0002846	Abnormal B cell morphology
HP:0003175	Hypoplastic ischia
HP:0003196	Short nose
HP:0003220	Abnormality of chromosome stability

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST001937_60	Breast cancer	3.000000e-08
GCST002148_1	Otitis media (chronic/recurrent)	2.000000e-08
GCST002182_1	End-stage renal disease in Type 1 diabetics	4.000000e-08
GCST002250_1	Blood pressure measurement (low sodium intervention)	4.000000e-08
GCST002250_6	Blood pressure measurement (low sodium intervention)	5.000000e-07
GCST002250_8	Blood pressure measurement (low sodium intervention)	7.000000e-06
GCST002252_1	Blood pressure measurement (high sodium and potassium intervention)	4.000000e-08
GCST002252_11	Blood pressure measurement (high sodium and potassium intervention)	6.000000e-06
GCST002252_5	Blood pressure measurement (high sodium and potassium intervention)	1.000000e-08
GCST003831_15	Asthma	4.000000e-06
GCST003983_44	Male-pattern baldness	5.000000e-08
GCST004744_27	Lung adenocarcinoma	2.000000e-06
GCST004748_73	Lung cancer	6.000000e-06
GCST004863_123	Mosquito bite size	2.000000e-07
GCST004988_191	Breast cancer	5.000000e-10
GCST005116_15	Male-pattern baldness	5.000000e-10
GCST006085_114	Prostate cancer	3.000000e-08
GCST007621_5	Sensation seeking	1.000000e-06
GCST009440_1	Age-related cognitive decline (attention/processing speed) (slope of z-scores)	7.000000e-06

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005402	response to low sodium diet
EFO:0006340	mean arterial pressure
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0005401	response to high sodium diet
EFO:0005403	response to dietary potassium supplementation
EFO:0008378	mosquito bite reaction size measurement
EFO:0006946	behavioural disinhibition measurement
EFO:0007710	cognitive decline measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537362	Immunodeficiency syndrome, variable (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression	6
Valproic Acid	increases expression, affects expression, decreases expression, affects cotreatment	5
sodium arsenite	decreases expression, increases abundance, increases expression	4
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, affects expression, decreases expression	4
bisphenol A	affects expression, increases expression, affects cotreatment, decreases expression	3
trichostatin A	affects cotreatment, increases expression	3
Tobacco Smoke Pollution	decreases expression	3
Aflatoxin B1	affects expression, decreases expression, increases expression	3
Cadmium Chloride	decreases expression, increases abundance	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Estradiol	increases expression	2
Tretinoin	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
afimoxifene	increases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
hydroquinone	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
monomethylpropion	increases expression	1
phenethyl isothiocyanate	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
K 7174	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SI12	HAP1 CDCA7 (-) 1	Cancer cell line	Male
CVCL_SI13	HAP1 CDCA7 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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