ATAD5

Summary

ATAD5 (ATPase family AAA domain containing 5, HGNC:25752) is a protein-coding gene on chromosome 17q11.2, encoding ATPase family AAA domain-containing protein 5 (Q96QE3). Has an important role in DNA replication and in maintaining genome integrity during replication stress.

Enables DNA clamp unloader activity. Involved in positive regulation of DNA replication and positive regulation of cell cycle G2/M phase transition. Part of Elg1 RFC-like complex. Biomarker of neurilemmoma.

Source: NCBI Gene 79915 — RefSeq curated summary.

At a glance

• GWAS associations: 36
• Clinical variants (ClinVar): 274 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_024857

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25752
Approved symbol	ATAD5
Name	ATPase family AAA domain containing 5
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12735, FRAG1, ELG1
Ensembl gene	ENSG00000176208
Ensembl biotype	protein_coding
OMIM	609534
Entrez	79915

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 non_stop_decay, 1 retained_intron

ENST00000321990, ENST00000578295, ENST00000585133, ENST00000933271, ENST00000933272

RefSeq mRNA: 1 — MANE Select: NM_024857 NM_024857

CCDS: CCDS11260

Canonical transcript exons

ENST00000321990 — 23 exons

Exon	Start	End
ENSE00001282400	30894564	30894722
ENSE00001282407	30893294	30894150
ENSE00001282414	30892607	30892788
ENSE00001282422	30887192	30887372
ENSE00001282429	30879423	30879487
ENSE00001282435	30878003	30878096
ENSE00001282441	30877416	30877549
ENSE00001282444	30876374	30876550
ENSE00001282450	30869496	30869646
ENSE00001282525	30834148	30836048
ENSE00001317821	30894835	30895869
ENSE00003470136	30856955	30857112
ENSE00003495483	30858161	30858323
ENSE00003538667	30843913	30844039
ENSE00003540311	30837206	30837314
ENSE00003580965	30869248	30869390
ENSE00003644930	30840617	30840781
ENSE00003650606	30868333	30868412
ENSE00003655787	30865704	30865800
ENSE00003657308	30860433	30860612
ENSE00003671641	30855143	30855327
ENSE00003686085	30844835	30844916
ENSE00003850234	30831966	30832413

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 85.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4898 / max 256.5557, expressed in 1204 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160159	6.4898	1204

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	85.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.27	gold quality
ventricular zone	UBERON:0003053	79.98	gold quality
ganglionic eminence	UBERON:0004023	77.07	gold quality
calcaneal tendon	UBERON:0003701	71.42	gold quality
embryo	UBERON:0000922	70.62	gold quality
tendon	UBERON:0000043	69.23	gold quality
stromal cell of endometrium	CL:0002255	68.95	gold quality
adrenal tissue	UBERON:0018303	68.70	gold quality
cortical plate	UBERON:0005343	68.26	gold quality
monocyte	CL:0000576	67.59	gold quality
mononuclear cell	CL:0000842	67.43	gold quality
rectum	UBERON:0001052	67.43	gold quality
leukocyte	CL:0000738	67.40	gold quality
bone marrow cell	CL:0002092	67.35	silver quality
colonic epithelium	UBERON:0000397	67.01	silver quality
lymph node	UBERON:0000029	66.48	gold quality
cerebellar hemisphere	UBERON:0002245	66.41	gold quality
cerebellar cortex	UBERON:0002129	66.40	gold quality
bone marrow	UBERON:0002371	66.18	gold quality
secondary oocyte	CL:0000655	65.71	silver quality
right hemisphere of cerebellum	UBERON:0014890	65.67	gold quality
tendon of biceps brachii	UBERON:0008188	65.07	gold quality
vermiform appendix	UBERON:0001154	64.81	gold quality
cerebellum	UBERON:0002037	64.12	gold quality
lower esophagus mucosa	UBERON:0035834	63.95	gold quality
granulocyte	CL:0000094	63.60	gold quality
esophagus mucosa	UBERON:0002469	63.60	gold quality
sural nerve	UBERON:0015488	63.04	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

104 targeting ATAD5, 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-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
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-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4666A-3P	99.96	71.71	3434

Literature-anchored findings (GeneRIF, showing 14)

• The Frag1 signal pathway, by linking replication stress surveillance with apoptosis induction, plays a central role in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis. (PMID:15983387)
• Human ELG1 protein is stabilized and localized to form foci at sites of stalled DNA replications that are different from DNA double strand breaks foci. (PMID:19755857)
• Studies indicate that USP1 and ELG1 as regulators of PCNA ubiquitylation. (PMID:21640107)
• loss-of-function mutations in mammalian Atad5 are sufficient to cause genomic instability and tumorigenesis. (PMID:21901109)
• ATAD5 regulates the cycle of DNA replication factories, probably through its PCNA-unloading activity. (PMID:23277426)
• Elg1 has an important role in maintaining chromosome integrity by regulating PCNA levels on chromatin, thereby acting as a PCNA unloading factor. (PMID:23937667)
• Authors discuss many functions of Elg1 protein as embryonic lethal when lost in mice, as a tumor suppressor in mice and humans, interacts with human Fanconi Anemia pathway and may contribute to some of the phenotypes associated with neurofibromatosis. [Review] (PMID:25795125)
• Report rare ATAD5 missense mutations may contribute to genetic susceptibility breast cancer and epithelial ovarian carcinoma. (PMID:27045477)
• ATAD5, a PCNA unloader, plays multiple functions at stalled forks including promoting its restart. ATAD5 depletion increases genomic instability upon hydroxyurea treatment in cultured cells and mice. ATAD5 recruits RAD51 to stalled forks in an ATR kinase-dependent manner by hydroxyurea-enhanced protein-protein interactions and timely removes PCNA from stalled forks for RAD51 recruitment. (PMID:31844045)
• ATAD5 restricts R-loop formation through PCNA unloading and RNA helicase maintenance at the replication fork. (PMID:32542338)
• ATAD5 suppresses centrosome over-duplication by regulating UAF1 and ID1. (PMID:32594826)
• Timely termination of repair DNA synthesis by ATAD5 is important in oxidative DNA damage-induced single-strand break repair. (PMID:34718749)
• Effects of Defective Unloading and Recycling of PCNA Revealed by the Analysis of ELG1 Mutants. (PMID:36675081)
• Short-range end resection requires ATAD5-mediated PCNA unloading for faithful homologous recombination. (PMID:37739427)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atad5a	ENSDARG00000070568
danio_rerio	atad5b	ENSDARG00000101126
mus_musculus	Atad5	ENSMUSG00000017550
rattus_norvegicus	Atad5	ENSRNOG00000021903
drosophila_melanogaster	elg1	FBGN0036574

Paralogs (1): CRLF3 (ENSG00000176390)

Protein

Protein identifiers

ATPase family AAA domain-containing protein 5 — Q96QE3 (reviewed: Q96QE3)

Alternative names: Chromosome fragility-associated gene 1 protein

All UniProt accessions (2): A0A075B754, Q96QE3

UniProt curated annotations — full annotation on UniProt →

Function. Has an important role in DNA replication and in maintaining genome integrity during replication stress. Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis. Modulates the RAD9A interaction with BCL2 and thereby induces DNA damage-induced apoptosis. Promotes PCNA deubiquitination by recruiting the ubiquitin-specific protease 1 (USP1) and WDR48 thereby down-regulating the error-prone damage bypass pathway. As component of the ATAD5 RFC-like complex, regulates the function of the DNA polymerase processivity factor PCNA by unloading the ring-shaped PCNA homotrimer from DNA after replication during the S phase of the cell cycle. This seems to be dependent on its ATPase activity. Plays important roles in restarting stalled replication forks under replication stress, by unloading the PCNA homotrimer from DNA and recruiting RAD51 possibly through an ATR-dependent manner. Ultimately this enables replication fork regression, breakage, and eventual fork restart. Both the PCNA unloading activity and the interaction with WDR48 are required to efficiently recruit RAD51 to stalled replication forks. Promotes the generation of MUS81-mediated single-stranded DNA-associated breaks in response to replication stress, which is an alternative pathway to restart stalled/regressed replication forks.

Subunit / interactions. Component of a heteropentameric replication factor ATAD5 RFC-like complex composed of one large subunit (ATAD5) and four small subunits (RFC2, RFC3, RFC4 and RFC5). Within the ATAD5 RFC-like complex, interacts with RFC2, RFC4 and RFC5. Within the ATAD5 RFC-like complex, interacts directly via-N terminal with RAD51; the interactions is enhanced under replication stress. Interacts with RB1 predominantly in G1 phase via its LXCXE motif. Interacts with RAD9A in growing cells. The interaction with RAD9A is reduced after exposure to DNA replication-inhibiting agents. Interacts with BRD4. Interacts with PCNA. Interacts with deubiquitinating enzyme USP1, and its associated factor, WDR48.

Subcellular location. Nucleus.

Post-translational modifications. ATR may stimulate the RAD9A dissociation.

Similarity. Belongs to the AAA ATPase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96QE3-1	1	yes
Q96QE3-2	2

RefSeq proteins (1): NP_079133* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00004

UniProt features (108 total): helix 29, strand 17, region of interest 11, modified residue 11, compositionally biased region 9, turn 7, sequence variant 7, mutagenesis site 7, sequence conflict 5, chain 1, short sequence motif 1, binding site 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8UII	ELECTRON MICROSCOPY	3.04
8UI8	ELECTRON MICROSCOPY	3.1
8UI9	ELECTRON MICROSCOPY	3.5
8UI7	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96QE3-F1	46.76	0.04

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 1132–1139

Post-translational modifications (12): 44, 219, 306, 311, 354, 369, 602, 614, 621, 817, 1116, 127

Mutagenesis-validated functional residues (7):

Position	Phenotype
368–384	abolishes interaction with wdr48 and recruitment of rad51 at site of stalled replication forks under replication stress.
642–645	loss of interaction with rad51 and loading of rad51 to stalled replication forks during replication stress. loss of proc
1138	results in defective pcna removal from chromatin and recruitment of rad51 at site of stalled replication forks under rep
1169	no effect on the rad9a interaction after mms exposure. resists to dna damage after mms exposure.
1187	weakly affects the rad9a interaction after mms exposure.
1430	abolishes rb1 binding. abolishes rb1 binding; when associated with k-1432. weakly detected after methyl methane-sulfonat
1432	abolishes rb1 binding; when associated with g-1430. expression detected after methyl methane-sulfonate (mms) treatment;

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 289 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, E2F_Q4, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, E2F4DP1_01, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_BY_P53_CLASS_MEDIATOR, GOBP_B_CELL_ACTIVATION, GOBP_CELL_CYCLE_DNA_REPLICATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_CELL_CYCLE_PHASE_TRANSITION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_B_CELL_PROLIFERATION

GO Biological Process (16): cell population proliferation (GO:0008283), positive regulation of B cell proliferation (GO:0030890), nuclear DNA replication (GO:0033260), signal transduction in response to DNA damage (GO:0042770), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), isotype switching (GO:0045190), positive regulation of DNA replication (GO:0045740), positive regulation of isotype switching to IgG isotypes (GO:0048304), regulation of mitotic cell cycle phase transition (GO:1901990), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:1902166), positive regulation of cell cycle G2/M phase transition (GO:1902751), DNA damage response (GO:0006974), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), positive regulation of DNA metabolic process (GO:0051054), regulation of cell cycle phase transition (GO:1901987), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902230)

GO Molecular Function (6): DNA binding (GO:0003677), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), DNA clamp unloader activity (GO:0061860), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), Elg1 RFC-like complex (GO:0031391)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA damage response	2
intrinsic apoptotic signaling pathway in response to DNA damage	2
cellular process	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
nucleus	1
cell cycle	1
cell cycle DNA replication	1
intracellular signal transduction	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
somatic recombination of immunoglobulin genes involved in immune response	1
B cell activation involved in immune response	1
DNA replication	1
regulation of DNA replication	1
positive regulation of DNA metabolic process	1
positive regulation of isotype switching	1
isotype switching to IgG isotypes	1
regulation of isotype switching to IgG isotypes	1
regulation of mitotic cell cycle	1
mitotic cell cycle phase transition	1
regulation of cell cycle phase transition	1
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1
regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1
cell cycle G2/M phase transition	1
positive regulation of cell cycle phase transition	1
regulation of cell cycle G2/M phase transition	1
cellular response to stress	1
intrinsic apoptotic signaling pathway	1
DNA metabolic process	1
positive regulation of macromolecule metabolic process	1
regulation of DNA metabolic process	1
regulation of cell cycle process	1
cell cycle phase transition	1
regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1
negative regulation of intrinsic apoptotic signaling pathway	1
nucleic acid binding	1

Protein interactions and networks

STRING

1836 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATAD5	RFC2	P32846	994
ATAD5	WDR48	Q8TAF3	928
ATAD5	RFC5	P40937	922
ATAD5	RAD17	O75943	914
ATAD5	CHTF18	Q8WVB6	877
ATAD5	RAD9A	Q99638	828
ATAD5	USP1	O94782	785
ATAD5	RAD52	P43351	780
ATAD5	FEN1	P39748	751
ATAD5	DSCC1	Q9BVC3	736
ATAD5	RAD51	Q06609	734
ATAD5	CHTF8	P0CG13	723
ATAD5	WDHD1	O75717	706
ATAD5	BRD4	O60885	685
ATAD5	RFC4	P35249	679

IntAct

58 interactions, top by confidence:

A	B	Type	Score
RFC5	RAD17	psi-mi:“MI:0914”(association)	0.730
RFC4	RAD17	psi-mi:“MI:0914”(association)	0.730
PCNA	POM121C	psi-mi:“MI:0914”(association)	0.550
MIS12	SPC24	psi-mi:“MI:0914”(association)	0.530
CA8	IGLL5	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
ATAD5	H2BC13	psi-mi:“MI:0915”(physical association)	0.400
ATAD5	H2BC14	psi-mi:“MI:0915”(physical association)	0.400
ATAD5	H3C13	psi-mi:“MI:0915”(physical association)	0.400
HSCB	ATAD5	psi-mi:“MI:0915”(physical association)	0.370
Ubr5	SFI1	psi-mi:“MI:0914”(association)	0.350
Set	ZKSCAN1	psi-mi:“MI:0914”(association)	0.350
NOP56	C12orf43	psi-mi:“MI:0914”(association)	0.350
BAX	BDP1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
RFC4	RAD1	psi-mi:“MI:0914”(association)	0.350
RFC5	RAD17	psi-mi:“MI:0914”(association)	0.350
BRD4	CST1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
HNRNPCL2	SMCHD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (124): ATAD5 (Proximity Label-MS), ATAD5 (Proximity Label-MS), ATAD5 (Affinity Capture-MS), ATAD5 (Affinity Capture-MS), ATAD5 (Affinity Capture-MS), ATAD5 (Affinity Capture-MS), ATAD5 (Affinity Capture-MS), ATAD5 (Affinity Capture-MS), ATAD5 (Proximity Label-MS), ATAD5 (Affinity Capture-MS), ATAD5 (Affinity Capture-MS), ATAD5 (Synthetic Lethality), ATAD5 (Synthetic Lethality), ATAD5 (Synthetic Lethality), ATAD5 (Synthetic Lethality)

ESM2 similar proteins: A0A087WXM9, A0A2K1JJ00, A0JM83, A4IGL8, E1BC15, E9Q5F9, O14513, O35923, O60673, O88491, P46013, P97929, Q14B71, Q28DZ0, Q29RT4, Q3MHH3, Q3TNU4, Q3ZBP0, Q4QY64, Q4V7J0, Q5DTT3, Q5E9A0, Q5F2C3, Q5RD08, Q5VWN6, Q5VYV7, Q61493, Q69YH5, Q6NS59, Q703I1, Q80U59, Q86XD8, Q8IXS0, Q8IYL3, Q8L7I1, Q8N7Z5, Q8NFU7, Q8TEP8, Q92628, Q96BU1

Diamond homologs: A0A7N9VSG0, A0B6D7, A1KU52, A1RSA2, A1RSA3, A1RV38, A1RWU6, A1RWU7, A2BL93, A2SQR6, A3CTR4, A3DNV8, A3DNV9, A3MS27, A4FZL6, A4WGV2, A4WGV3, A4WLY0, A5UMF4, A6URV8, A6UWR5, A6VIW1, A7I4H6, A7YSY2, A8AC24, A9A6N2, A9LZC3, B0R601, B1YC69, B4RLV8, B9LPV1, C3MQ13, C3MVD2, C3N5N1, C3NE95, C3NHF4, C4KHA7, D4A2B7, F2Z6D2, O26342

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CDK1	“down-regulates activity”	ATAD5	phosphorylation
ATAD5	up-regulates	BRD4	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 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
RNA Polymerase I Promoter Opening	6	21.7×	1e-05
ChAHP complex assembly	6	21.7×	1e-05
G2/M DNA damage checkpoint	9	21.2×	9e-08
DNA methylation	6	21.0×	1e-05
FXIIa activates plasma kallikrein-kinin system	6	20.4×	1e-05
Processing of DNA double-strand break ends	9	20.1×	9e-08
SIRT1 negatively regulates rRNA expression	6	20.1×	1e-05
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	6	19.8×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	7	14.9×	2e-04
DNA repair	8	7.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	191
Likely benign	34
Benign	24

Top pathogenic / likely-pathogenic (0)

SpliceAI

3550 predictions. Top by Δscore:

Variant	Effect	Δscore
17:30837204:A:AG	acceptor_gain	1.0000
17:30837205:G:GG	acceptor_gain	1.0000
17:30837205:GA:G	acceptor_gain	1.0000
17:30840612:TTTAG:T	acceptor_loss	1.0000
17:30840614:TA:T	acceptor_loss	1.0000
17:30840615:A:AG	acceptor_gain	1.0000
17:30840616:G:GA	acceptor_loss	1.0000
17:30840616:G:GG	acceptor_gain	1.0000
17:30840616:GGCAA:G	acceptor_gain	1.0000
17:30840777:CAGAA:C	donor_gain	1.0000
17:30840778:AGAA:A	donor_gain	1.0000
17:30840779:GAA:G	donor_gain	1.0000
17:30840779:GAAG:G	donor_gain	1.0000
17:30840781:AG:A	donor_loss	1.0000
17:30840782:G:GG	donor_gain	1.0000
17:30840783:TAA:T	donor_loss	1.0000
17:30844050:T:G	donor_gain	1.0000
17:30855125:A:AG	acceptor_gain	1.0000
17:30855126:A:G	acceptor_gain	1.0000
17:30855130:A:AG	acceptor_gain	1.0000
17:30855131:T:G	acceptor_gain	1.0000
17:30855138:A:AG	acceptor_gain	1.0000
17:30855141:A:G	acceptor_gain	1.0000
17:30855142:G:GG	acceptor_gain	1.0000
17:30855142:GTCAA:G	acceptor_gain	1.0000
17:30855327:GGTA:G	donor_loss	1.0000
17:30855328:G:C	donor_loss	1.0000
17:30855329:T:A	donor_loss	1.0000
17:30856950:TTTA:T	acceptor_loss	1.0000
17:30856951:TTAG:T	acceptor_loss	1.0000

AlphaMissense

12288 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:30869320:T:C	L1129P	1.000
17:30869551:T:C	L1171S	1.000
17:30869559:G:C	A1174P	1.000
17:30877533:T:C	L1301P	1.000
17:30878076:C:A	P1331H	1.000
17:30878085:T:C	L1334P	1.000
17:30868334:T:A	W1079R	0.999
17:30868334:T:C	W1079R	0.999
17:30868338:T:C	L1080S	0.999
17:30868346:T:A	W1083R	0.999
17:30868346:T:C	W1083R	0.999
17:30869317:T:A	V1128D	0.999
17:30869328:G:A	G1132R	0.999
17:30869328:G:C	G1132R	0.999
17:30869328:G:T	G1132W	0.999
17:30869329:G:A	G1132E	0.999
17:30869371:C:A	A1146D	0.999
17:30869386:T:C	F1151S	0.999
17:30869523:C:A	R1162S	0.999
17:30869530:G:A	G1164D	0.999
17:30869542:T:C	L1168P	0.999
17:30877533:T:A	L1301H	0.999
17:30877536:T:A	I1302N	0.999
17:30877536:T:C	I1302T	0.999
17:30877536:T:G	I1302S	0.999
17:30877539:T:C	L1303P	0.999
17:30877542:T:C	F1304S	0.999
17:30877545:A:T	E1305V	0.999
17:30878033:T:C	F1317L	0.999
17:30878034:T:C	F1317S	0.999

dbSNP variants (sampled 300 via entrez): RS1000016592 (17:30885958 A>T), RS1000064649 (17:30888215 T>C), RS1000178142 (17:30861307 T>G), RS1000179014 (17:30845951 A>C), RS1000267898 (17:30881095 T>C), RS1000276862 (17:30832219 G>A), RS1000292196 (17:30853155 G>T), RS1000324783 (17:30879640 G>A), RS1000329367 (17:30872089 AT>A,ATT), RS1000330376 (17:30880301 T>G), RS1000369626 (17:30845911 C>T), RS1000442434 (17:30860681 G>A), RS1000473542 (17:30860272 C>G,T), RS1000489115 (17:30838660 T>G), RS1000506094 (17:30859988 T>C)

Disease associations

OMIM: gene MIM:609534 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

36 associations (top):

Study	Trait	p-value
GCST000175_4	Height	2.000000e-09
GCST001956_58	Height	9.000000e-14
GCST004067_118	Hip circumference adjusted for BMI	2.000000e-12
GCST004067_155	Hip circumference adjusted for BMI	8.000000e-09
GCST004067_49	Hip circumference adjusted for BMI	3.000000e-06
GCST004562_187	Waist circumference adjusted for body mass index	4.000000e-08
GCST004562_50	Waist circumference adjusted for body mass index	5.000000e-08
GCST004563_136	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-06
GCST004563_201	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-07
GCST004564_126	Waist circumference adjusted for BMI in active individuals	4.000000e-07
GCST004564_127	Waist circumference adjusted for BMI in active individuals	9.000000e-06
GCST004599_120	Mean platelet volume	3.000000e-09
GCST004608_220	Granulocyte percentage of myeloid white cells	1.000000e-09
GCST004633_42	Neutrophil percentage of white cells	3.000000e-09
GCST004749_48	Lung cancer in ever smokers	7.000000e-06
GCST004904_189	Body mass index	3.000000e-08
GCST004950_38	Breast cancer	3.000000e-08
GCST004988_205	Breast cancer	2.000000e-09
GCST006630_78	Diastolic blood pressure	9.000000e-10
GCST007236_74	Breast cancer	1.000000e-06
GCST007485_8	Anthropometric traits	2.000000e-71
GCST007490_27	Anthropometric traits (multi-trait analysis)	8.000000e-46
GCST008161_112	Waist circumference adjusted for body mass index	3.000000e-07
GCST008362_21	Birth weight	2.000000e-13
GCST012226_794	Waist circumference adjusted for body mass index	3.000000e-23
GCST012227_334	Hip circumference adjusted for BMI	9.000000e-15
GCST90000025_580	Appendicular lean mass	5.000000e-12
GCST90000025_581	Appendicular lean mass	2.000000e-101
GCST90002390_109	Mean corpuscular hemoglobin	1.000000e-14
GCST90002390_110	Mean corpuscular hemoglobin	1.000000e-34

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004340	body mass index
EFO:0006336	diastolic blood pressure
EFO:0004324	body weights and measures
EFO:0004344	birth weight
EFO:0004980	appendicular lean mass
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741209 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.72	Kd	19	nM	MOLIBRESIB
7.30	IC50	50	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179107: Binding affinity against ATAD5 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0190	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	6
sodium arsenite	increases expression	3
trichostatin A	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression	2
Lead	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
phenethyl isothiocyanate	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Calcitriol	decreases expression, affects cotreatment	1
Cannabidiol	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Methyl Methanesulfonate	increases expression	1

ChEMBL screening assays

21 unique, capped per target: 13 functional, 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1737868	Functional	PUBCHEM_BIOASSAY: Validation screen for small molecules that induce genotoxicity in human embryonic kidney (HEK293T) cells expressing luciferase-tagged ELG1. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID4931	PubChem BioAssay data set
CHEMBL3214864	Binding	PubChem BioAssay. qHTS screen for small molecules that inhibit ELG1-dependent DNA repair: SAR in Biochemical Luciferin Assay. (Class of assay: confirmatory)	PubChem BioAssay data set

Clinical trials (associated diseases)

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