DFFB

Summary

DFFB (DNA fragmentation factor subunit beta, HGNC:2773) is a protein-coding gene on chromosome 1p36.32, encoding DNA fragmentation factor subunit beta (O76075). Nuclease that induces DNA fragmentation and chromatin condensation during apoptosis.

Apoptosis is a cell death process that removes toxic and/or useless cells during mammalian development. The apoptotic process is accompanied by shrinkage and fragmentation of the cells and nuclei and degradation of the chromosomal DNA into nucleosomal units. DNA fragmentation factor (DFF) is a heterodimeric protein of 40-kD (DFFB) and 45-kD (DFFA) subunits. DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. DFF becomes activated when DFFA is cleaved by caspase-3. The cleaved fragments of DFFA dissociate from DFFB, the active component of DFF. DFFB has been found to trigger both DNA fragmentation and chromatin condensation during apoptosis. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene but the biological validity of some of these variants has not been determined.

Source: NCBI Gene 1677 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_004402

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2773
Approved symbol	DFFB
Name	DNA fragmentation factor subunit beta
Location	1p36.32
Locus type	gene with protein product
Status	Approved
Aliases	CAD, CPAN, DFF-40, DFF40
Ensembl gene	ENSG00000169598
Ensembl biotype	protein_coding
OMIM	601883
Entrez	1677

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 nonsense_mediated_decay, 5 protein_coding, 1 retained_intron

ENST00000338895, ENST00000339350, ENST00000378206, ENST00000378209, ENST00000461150, ENST00000468793, ENST00000475969, ENST00000477548, ENST00000481945, ENST00000491998, ENST00000625756, ENST00000894547, ENST00000919095

RefSeq mRNA: 4 — MANE Select: NM_004402 NM_001282669, NM_001320132, NM_001320136, NM_004402

CCDS: CCDS52, CCDS72693

Canonical transcript exons

ENST00000378209 — 7 exons

Exon	Start	End
ENSE00000000197	3857476	3857717
ENSE00001762006	3858718	3858844
ENSE00003478508	3872472	3872572
ENSE00003478711	3869605	3869775
ENSE00003514398	3867974	3868053
ENSE00003606040	3883507	3885429
ENSE00003683567	3865812	3866000

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 84.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.0740 / max 40.0402, expressed in 1471 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
329	2.9194	967
328	1.1546	805

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	84.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.15	gold quality
cerebellar cortex	UBERON:0002129	84.12	gold quality
cerebellum	UBERON:0002037	82.69	gold quality
granulocyte	CL:0000094	81.67	gold quality
endothelial cell	CL:0000115	81.33	silver quality
calcaneal tendon	UBERON:0003701	79.65	gold quality
adenohypophysis	UBERON:0002196	79.13	gold quality
right ovary	UBERON:0002118	78.95	gold quality
mucosa of transverse colon	UBERON:0004991	78.77	gold quality
cortical plate	UBERON:0005343	78.77	gold quality
pituitary gland	UBERON:0000007	78.74	gold quality
left ovary	UBERON:0002119	78.33	gold quality
body of pancreas	UBERON:0001150	78.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.10	gold quality
monocyte	CL:0000576	78.02	gold quality
leukocyte	CL:0000738	77.82	gold quality
mononuclear cell	CL:0000842	77.73	gold quality
spleen	UBERON:0002106	77.56	gold quality
duodenum	UBERON:0002114	77.30	gold quality
right frontal lobe	UBERON:0002810	77.25	gold quality
jejunal mucosa	UBERON:0000399	77.21	gold quality
right lobe of liver	UBERON:0001114	77.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.82	gold quality
stromal cell of endometrium	CL:0002255	76.77	gold quality
endocervix	UBERON:0000458	76.75	gold quality
primary visual cortex	UBERON:0002436	76.42	gold quality
nucleus accumbens	UBERON:0001882	76.36	gold quality
body of uterus	UBERON:0009853	76.32	gold quality
ovary	UBERON:0000992	76.29	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	13.84
E-ANND-3	no	2.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SPI1

miRNA regulators (miRDB)

86 targeting DFFB, 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-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-7856-5P	99.75	69.99	2901

Literature-anchored findings (GeneRIF, showing 40)

• Mutations and aberrantly spliced transcripts for the CAD gene are frequently associated with hepatocellular carcinoma. (PMID:12610505)
• Hsp70 binds free CAD in TCR-stimulated T cells to stabilize and augment its activity. (PMID:12738667)
• subunit structures and stoichiometries in human cells before and after induction of apoptosis (PMID:12748178)
• CAD involves unrestricted accessibility of chromosomal DNA at the initial phase of apoptosis, followed by its nuclear immobilization that may prevent the release of the active nuclease into the extracellular environment. (PMID:15569712)
• PARP-1 poly(ADP-ribosyl)ation is a terminal event in the apoptotic response that occurs in response to DNA fragmentation and directly influences DFF40 activity (PMID:15703174)
• Interactions identified here between human placenta histone H1 carboxyl-terminal domain and DFF40/CAD target and activate linker DNA cleavage during the terminal stages of apoptosis. (PMID:15910001)
• Our findings of high frequency of Alu-mediated hCAD deletion in human hepatoma underscore the implication of hCAD in hepatocarcinogenesis (PMID:16007181)
• AIF is responsible for stage I nuclear morphology and HMW DNA degradation is a caspase-activated DNase and AIF-independent process (PMID:16049016)
• levels of CAD were significantly higher in the nuclear fraction of temporal lobe epilepsy samples (PMID:16121124)
• DFFB haploinsufficiency from 1p allelic loss is a contributing factor in oligodendroglioma development (PMID:16156899)
• in apoptotic cells, endogenous and exogenous CAD forms limited oligomers, representing the active nuclease (PMID:16204257)
• the N-terminal region was found to be responsible for the requirement of salt for fibril formation (PMID:16428311)
• CAD is downregulated at the mRNA and protein level during the erythroid differentiation in TF-1 cells. (PMID:16529748)
• poly-glutamic acid and heparin inhibit DFF40/CAD, the latter one being highly effective at nanomolar concentrations. The inhibitory poly-anions bind to the nuclease and impair its ability to bind double-stranded DNA. (PMID:16699957)
• These results suggest that CAD is the endogenous endonuclease that mediates internucleosomal DNA degradation in rotenone-induced apoptosis. (PMID:17239993)
• Data suggest that erythroblast chromatin degradation may involve caspase activated DNase and apoptosis inducing factor, enzymes distinct from those active in apoptotic cells. (PMID:17492772)
• C-terminal region of each subunit, DFF40 (RLKRK) and DFF45 (KRAR), is essential for nuclear accumulation of the DFF complex. (PMID:17938174)
• changes induced in DNA conformation upon HMG-box binding makes the substrate more accessible to cleavage by DFF40/CAD nuclease and thus may contribute to preferential linker DNA cleavage during apoptosis (PMID:18239742)
• We have found that neither single-stranded DNA, single-stranded RNA, double-stranded RNA nor RNA-DNA heteroduplexes are cleaved by the DFF40/CAD nuclease. (PMID:18283539)
• The heterodimer, DFF40-DFF45, is localized to the chromatin fraction under apoptotic as well as non-apoptotic conditions. (PMID:19882353)
• These data suggest that DFF 40 mediated apoptosis plays a significant role in mediating sepsis induced cellular dysfunction. (PMID:21820410)
• Data show that among the 13 SNPs in the 3 genes, only 3 were found to be polymorphic: R196K and K277R in the DFFB gene, and S12L in the EndoG gene, and all 6 SNPs in the FEN-1 gene were entirely monoallelic. (PMID:22011247)
• During apoptotic rearrangement of interchromatin granule clusters, the nuclear matrix (NuMa rearrangement) and chromatin are closely associated. This process occurs in defined stages and depends on the activity of protein phosphatases, caspases and CAD. (PMID:22023725)
• the cytosolic levels of DFF40/CAD are determinants in achieving a complete apoptotic phenotype, including oligonucleosomal DNA degradation. (PMID:22253444)
• Human papillomavirus type 16 E6 protein inhibits DNA fragmentation via interaction with DNA fragmentation factor 40 (PMID:22609799)
• These results suggest a cooperative activity between CAD and DNAS1L3 to accomplish internucleosomal DNA fragmentation . (PMID:23229555)
• the highest order of chromatin compaction observed in the later steps of caspase-dependent apoptosis relies on DFF40/CAD-mediated DNA damage by generating 3’-OH ends in single-strand rather than double-strand DNA nicks/breaks (PMID:23430749)
• DFF40/CAD-independent mechanism driving conformational nuclear changes during caspase-dependent cell death (PMID:24838313)
• Combinatorial use of some sulfonamides such as acetazolamide along with increased expression of DFF40 can potently kill tumor cells via apoptosis. (PMID:25086620)
• Data show that the caspase-activated DNase (CAD) is activated when caspases cleave its endogenous inhibitor ICAD, resulting in the characteristic DNA laddering of apoptosis. (PMID:26106156)
• Data suggest DFF40 expression in breast cancer cell line is involved in drug sensitivity/resistance to doxorubicin; apoptotic cell death due to doxorubicin (a topoisomerase II inhibitor) is enhanced by DFF40 overexpression in breast cancer cell line. (PMID:26529233)
• the low expression levels of DFF40/CAD and the absence of DNA laddering as common molecular traits in glioblastoma (PMID:26755073)
• Dff40 expression is upregulated in atherosclerotic plaque. (PMID:28007744)
• Glandular, menopause-independent DFF40, DFF45, and Bcl-2 overexpression may play an important role in the pathogenesis of endometrial polyps and benign endometrial hyperplasia (PMID:28914671)
• we show that executioner caspase activation of the apoptotic nuclease CAD/DFF40 is essential for TRAIL-induced mutations in surviving cells. As exposure to chemotherapy drugs also activates apoptotic caspases and presumably CAD, we hypothesized that these pathways may also contribute to the mutagenesis induced by conventional chemotherapy drugs, perhaps augmenting the mutations that arise from direct DNA damage (PMID:28981092)
• The role of the DFF40/CAD endonuclease in genomic stability. (PMID:33387146)
• The Nexus of cfDNA and Nuclease Biology. (PMID:34006390)
• DFF40 deficiency in cancerous T cells is implicated in chemotherapy drug sensitivity and resistance through the regulation of the apoptotic pathway. (PMID:34678222)
• Spontaneous activity of the mitochondrial apoptosis pathway drives chromosomal defects, the appearance of micronuclei and cancer metastasis through the Caspase-Activated DNAse. (PMID:35393399)
• MEG3 Regulates CSE-Induced Apoptosis by Regulating miR-421/DFFB Signal Axis. (PMID:37215747)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dffb	ENSDARG00000009748
mus_musculus	Dffb	ENSMUSG00000029027
rattus_norvegicus	Dffb	ENSRNOG00000025030
drosophila_melanogaster	Drep4	FBGN0028406

Protein

Protein identifiers

DNA fragmentation factor subunit beta — O76075 (reviewed: O76075)

Alternative names: Caspase-activated deoxyribonuclease, Caspase-activated nuclease, DNA fragmentation factor 40 kDa subunit

All UniProt accessions (6): B4DZS0, O76075, G3XAD0, J3KT26, Q96P72, Q96P73

UniProt curated annotations — full annotation on UniProt →

Function. Nuclease that induces DNA fragmentation and chromatin condensation during apoptosis. Degrades naked DNA and induces apoptotic morphology.

Subunit / interactions. Heterodimer of DFFA and DFFB. Interacts with H1-1.

Subcellular location. Cytoplasm. Nucleus.

Activity regulation. Inhibited by DFFA (DFF45).

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (4)

UniProt ID	Names	Canonical?
O76075-1	Alpha	yes
O76075-2	Beta
O76075-3	Gamma
O76075-4	Delta

RefSeq proteins (4): NP_001269598, NP_001307061, NP_001307065, NP_004393* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003508	CIDE-N_dom	Domain
IPR015311	DFF40_C	Domain
IPR039729	DFF40	Family
IPR044925	His-Me_finger_sf	Homologous_superfamily

Pfam: PF02017, PF09230

UniProt features (17 total): strand 6, splice variant 5, sequence variant 2, chain 1, domain 1, helix 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1IBX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76075-F1	92.60	0.83

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-140342	Apoptosis induced DNA fragmentation

MSigDB gene sets: 550 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_APOPTOSIS_INDUCED_DNA_FRAGMENTATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOMF_ENDONUCLEASE_ACTIVITY, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_RESPONSE_TO_AMINE, GOMF_NUCLEASE_ACTIVITY, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MATTIOLI_MGUS_VS_PCL

GO Biological Process (5): DNA catabolic process (GO:0006308), apoptotic DNA fragmentation (GO:0006309), apoptotic chromosome condensation (GO:0030263), negative regulation of apoptotic DNA fragmentation (GO:1902511), apoptotic process (GO:0006915)

GO Molecular Function (10): DNA binding (GO:0003677), DNA endonuclease activity (GO:0004520), DNA nuclease activity (GO:0004536), hydrolase activity (GO:0016787), enzyme binding (GO:0019899), identical protein binding (GO:0042802), nuclease activity (GO:0004518), protein binding (GO:0005515), protein domain specific binding (GO:0019904), disordered domain specific binding (GO:0097718)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), protein-containing complex (GO:0032991), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Apoptotic execution phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein binding	3
DNA nuclease activity	2
apoptotic nuclear changes	2
nuclear lumen	2
DNA metabolic process	1
nucleic acid catabolic process	1
DNA catabolic process	1
chromosome condensation	1
apoptotic DNA fragmentation	1
regulation of apoptotic DNA fragmentation	1
negative regulation of DNA catabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nucleic acid binding	1
endonuclease activity	1
nuclease activity	1
catalytic activity, acting on DNA	1
catalytic activity	1
catalytic activity, acting on a nucleic acid	1
binding	1
protein domain specific binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
cellular_component	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

626 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DFFB	DFFA	O00273	999
DFFB	CASP3	P42574	914
DFFB	CIDEB	Q9UHD4	904
DFFB	ACIN1	Q9UKV3	875
DFFB	CIDEA	O60543	843
DFFB	DNASE2	O00115	838
DFFB	H1-0	P07305	813
DFFB	CASP6	P55212	720
DFFB	ENDOG	Q14249	706
DFFB	CASP14	P31944	635
DFFB	APAF1	O14727	626
DFFB	CASP9	P55211	624
DFFB	CYCS	P00001	623
DFFB	FADD	Q13158	616
DFFB	CASP8	Q14790	612

IntAct

34 interactions, top by confidence:

A	B	Type	Score
MAGOH	CASC3	psi-mi:“MI:0914”(association)	0.970
DFFA	DFFB	psi-mi:“MI:0915”(physical association)	0.940
DFFA	DFFB	psi-mi:“MI:0407”(direct interaction)	0.940
DFFA	DFFB	psi-mi:“MI:0914”(association)	0.940
DFFB	DFFA	psi-mi:“MI:0914”(association)	0.940
DFFB	DFFA	psi-mi:“MI:0915”(physical association)	0.940
BMI1	CBX4	psi-mi:“MI:0914”(association)	0.900
DFFB	UBB	psi-mi:“MI:0914”(association)	0.530
PARP2	DFFB	psi-mi:“MI:0557”(adp ribosylation reaction)	0.440
DFFB	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
DFFB	VIM	psi-mi:“MI:0915”(physical association)	0.400
DFFA	DFFB	psi-mi:“MI:0914”(association)	0.350
DFFB	H1-0	psi-mi:“MI:0914”(association)	0.350
FAM111A	DFFA	psi-mi:“MI:0914”(association)	0.350
HRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
HRAS	IGHV1-45	psi-mi:“MI:0914”(association)	0.350
NRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
KRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
KRAS		psi-mi:“MI:0914”(association)	0.350
DDX55	U2SURP	psi-mi:“MI:2364”(proximity)	0.270
EXOSC5	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
LIN28B	MEX3A	psi-mi:“MI:2364”(proximity)	0.270
SF3B4	MED19	psi-mi:“MI:2364”(proximity)	0.270
SUPV3L1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (43): DFFA (Co-fractionation), DFFB (Affinity Capture-MS), DFFB (Affinity Capture-MS), DFFB (Affinity Capture-MS), DFFB (Affinity Capture-MS), PTPN13 (Affinity Capture-MS), UBB (Affinity Capture-MS), LRRC15 (Affinity Capture-MS), PKN2 (Affinity Capture-MS), PRKACB (Affinity Capture-MS), NEFH (Affinity Capture-MS), DFFB (Affinity Capture-RNA), DFFB (Affinity Capture-MS), DFFB (Two-hybrid), DFFB (Reconstituted Complex)

ESM2 similar proteins: A0A2R8Y7D0, A3KMV1, A6NDN8, B9EHT4, D3YWQ0, F1MAB7, O23702, O54788, O75426, O76075, P04413, P0C5J9, P49897, P55073, Q1LZC5, Q28969, Q2T9Z2, Q2VPJ9, Q39491, Q3MHJ7, Q3TGW2, Q4R327, Q57VU6, Q58CZ0, Q5BIR3, Q5I3B1, Q5R4R7, Q5R686, Q5SPX3, Q5XI74, Q6DN07, Q6NXT1, Q6P7W2, Q6QN11, Q6X4W1, Q7L9B9, Q7TPD7, Q80TL4, Q8K485, Q8TBC3

Diamond homologs: O54788, O76075, Q58CZ0, Q99N34

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
“Caspase 3 complex”	up-regulates	DFFB	cleavage
DFFA	down-regulates	DFFB	binding
CASP3	up-regulates	DFFB	cleavage
DFFB	up-regulates	DNA_fragmentation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 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
Metabolism of RNA	5	9.9×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1453 predictions. Top by Δscore:

Variant	Effect	Δscore
1:3857654:G:GT	donor_gain	1.0000
1:3857685:G:GT	donor_gain	1.0000
1:3858840:GGGCT:G	donor_gain	1.0000
1:3858841:GGCT:G	donor_gain	1.0000
1:3858841:GGCTG:G	donor_gain	1.0000
1:3858842:GCT:G	donor_gain	1.0000
1:3858842:GCTG:G	donor_gain	1.0000
1:3858845:G:GG	donor_gain	1.0000
1:3865803:T:A	acceptor_gain	1.0000
1:3868051:G:T	donor_gain	1.0000
1:3869601:CCAG:C	acceptor_loss	1.0000
1:3869602:CAG:C	acceptor_loss	1.0000
1:3869603:AG:A	acceptor_gain	1.0000
1:3869603:AGGT:A	acceptor_gain	1.0000
1:3869604:GG:G	acceptor_gain	1.0000
1:3869604:GGT:G	acceptor_gain	1.0000
1:3869604:GGTG:G	acceptor_gain	1.0000
1:3869604:GGTGA:G	acceptor_gain	1.0000
1:3869775:GGT:G	donor_loss	1.0000
1:3869776:G:GC	donor_loss	1.0000
1:3869776:G:GG	donor_gain	1.0000
1:3869777:T:A	donor_loss	1.0000
1:3857701:G:T	donor_gain	0.9900
1:3858842:G:T	donor_gain	0.9900
1:3865801:ATT:A	acceptor_gain	0.9900
1:3865996:TGAAG:T	donor_loss	0.9900
1:3865998:AAG:A	donor_loss	0.9900
1:3865999:AGG:A	donor_loss	0.9900
1:3866001:G:GA	donor_loss	0.9900
1:3866002:T:G	donor_loss	0.9900

AlphaMissense

2220 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:3872556:T:A	W256R	0.999
1:3872556:T:C	W256R	0.999
1:3867999:G:C	K152N	0.998
1:3867999:G:T	K152N	0.998
1:3883643:C:G	H307D	0.998
1:3865991:T:A	W141R	0.997
1:3865991:T:C	W141R	0.997
1:3865994:T:C	F142L	0.997
1:3865996:T:A	F142L	0.997
1:3865996:T:G	F142L	0.997
1:3869764:T:C	F224L	0.997
1:3869766:C:A	F224L	0.997
1:3869766:C:G	F224L	0.997
1:3872516:C:A	N242K	0.997
1:3872516:C:G	N242K	0.997
1:3872558:G:C	W256C	0.997
1:3872558:G:T	W256C	0.997
1:3883640:T:C	C306R	0.997
1:3865993:G:C	W141C	0.996
1:3865993:G:T	W141C	0.996
1:3869765:T:C	F224S	0.996
1:3872478:T:C	F230L	0.996
1:3872480:T:A	F230L	0.996
1:3872480:T:G	F230L	0.996
1:3872518:C:A	P243H	0.996
1:3872548:T:C	F253S	0.996
1:3872566:A:T	D259V	0.996
1:3872568:C:G	H260D	0.996
1:3872570:C:A	H260Q	0.996
1:3872570:C:G	H260Q	0.996

dbSNP variants (sampled 300 via entrez): RS1000080745 (1:3855717 C>T), RS1000102654 (1:3857280 T>A,C), RS1000220241 (1:3881297 C>T), RS1000304323 (1:3876206 A>G), RS1000436074 (1:3871157 G>A), RS1000443542 (1:3868831 C>T), RS1000459813 (1:3861143 G>C), RS1000493968 (1:3861893 G>A,T), RS1000514058 (1:3857163 C>T), RS1000565135 (1:3856977 C>CG), RS1000787460 (1:3866970 A>C,G), RS1000963475 (1:3882814 C>T), RS1001051446 (1:3855661 T>C), RS1001279043 (1:3877364 CTG>C), RS1001310059 (1:3877077 T>G)

Disease associations

OMIM: gene MIM:601883 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002041_1	Blood trace element (Cu levels)	5.000000e-10
GCST009391_1721	Metabolite levels	8.000000e-06
GCST009391_2109	Metabolite levels	7.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005267	serum copper measurement
EFO:0010341	cholesteryl ester 16:0 measurement
EFO:0010381	phosphatidylcholine 36:3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	increases expression, affects binding, decreases reaction, decreases expression	3
Cisplatin	affects cotreatment, increases expression, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression	2
Copper	decreases expression, affects binding	2
Rotenone	decreases expression, affects response to substance	2
Tetrachlorodibenzodioxin	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
alpha phellandrene	increases expression	1
bisphenol A	decreases expression, increases methylation	1
tributyltin	decreases expression, increases reaction, increases cleavage, increases expression, increases response to substance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
aflatoxin B2	decreases methylation	1
hydroquinone	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
usnic acid	increases expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
motexafin gadolinium	decreases expression, affects cotreatment	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1M7	Abcam K-562 DFFB KO	Cancer cell line	Female
CVCL_D2IS	Abcam Raji DFFB KO	Cancer cell line	Male
CVCL_UQ39	Abcam Jurkat DFFB KO	Cancer cell line	Male

Clinical trials (associated diseases)

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