HUS1

Summary

HUS1 (HUS1 checkpoint clamp component, HGNC:5309) is a protein-coding gene on chromosome 7p12.3, encoding Checkpoint protein HUS1 (O60921). Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. It is a selective cancer dependency (DepMap: 49.5% of cell lines).

The protein encoded by this gene is a component of an evolutionarily conserved, genotoxin-activated checkpoint complex that is involved in the cell cycle arrest in response to DNA damage. This protein forms a heterotrimeric complex with checkpoint proteins RAD9 and RAD1. In response to DNA damage, the trimeric complex interacts with another protein complex consisting of checkpoint protein RAD17 and four small subunits of the replication factor C (RFC), which loads the combined complex onto the chromatin. The DNA damage induced chromatin binding has been shown to depend on the activation of the checkpoint kinase ATM, and is thought to be an early checkpoint signaling event. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3364 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 52 total
• Cancer dependency (DepMap): dependent in 49.5% of screened cell lines
• MANE Select transcript: NM_004507

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5309
Approved symbol	HUS1
Name	HUS1 checkpoint clamp component
Location	7p12.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000136273
Ensembl biotype	protein_coding
OMIM	603760
Entrez	3364

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000258774, ENST00000432325, ENST00000432627, ENST00000433977, ENST00000442024, ENST00000446009, ENST00000458191, ENST00000468868, ENST00000857243, ENST00000857244, ENST00000857245, ENST00000921484, ENST00000921485, ENST00000921486, ENST00000921487, ENST00000967541

RefSeq mRNA: 2 — MANE Select: NM_004507 NM_001363683, NM_004507

CCDS: CCDS34635, CCDS87501

Canonical transcript exons

ENST00000258774 — 8 exons

Exon	Start	End
ENSE00000683019	47969219	47969318
ENSE00000683020	47967806	47967925
ENSE00000832708	47976730	47976837
ENSE00001819062	47979468	47979615
ENSE00001884471	47963288	47965438
ENSE00002236131	47978417	47978593
ENSE00003488184	47975613	47975687
ENSE00003694200	47978689	47978816

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 90.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.2875 / max 580.5393, expressed in 1806 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84076	14.9831	1800
84077	6.3044	1701

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.88	gold quality
monocyte	CL:0000576	89.76	gold quality
mononuclear cell	CL:0000842	89.11	gold quality
leukocyte	CL:0000738	88.79	gold quality
sural nerve	UBERON:0015488	88.69	gold quality
calcaneal tendon	UBERON:0003701	88.51	gold quality
islet of Langerhans	UBERON:0000006	87.97	gold quality
adrenal tissue	UBERON:0018303	87.26	gold quality
rectum	UBERON:0001052	86.40	gold quality
colonic epithelium	UBERON:0000397	85.81	gold quality
muscle of leg	UBERON:0001383	85.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.56	gold quality
gastrocnemius	UBERON:0001388	85.22	gold quality
stromal cell of endometrium	CL:0002255	84.91	gold quality
granulocyte	CL:0000094	84.86	gold quality
tendon	UBERON:0000043	84.09	gold quality
ventricular zone	UBERON:0003053	83.98	gold quality
mucosa of transverse colon	UBERON:0004991	83.96	gold quality
right adrenal gland cortex	UBERON:0035827	83.72	gold quality
right adrenal gland	UBERON:0001233	83.58	gold quality
left adrenal gland	UBERON:0001234	83.22	gold quality
adrenal gland	UBERON:0002369	83.14	gold quality
pancreas	UBERON:0001264	83.02	gold quality
esophagus mucosa	UBERON:0002469	83.01	gold quality
left adrenal gland cortex	UBERON:0035825	82.65	gold quality
heart left ventricle	UBERON:0002084	82.64	gold quality
ganglionic eminence	UBERON:0004023	82.54	gold quality
skeletal muscle organ	UBERON:0014892	82.37	gold quality
muscle organ	UBERON:0001630	82.36	gold quality
omental fat pad	UBERON:0010414	82.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1

miRNA regulators (miRDB)

86 targeting HUS1, 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-4455	100.00	65.48	1587
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-570-3P	99.96	72.41	4910
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-1305	99.91	71.43	3443
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-548BB-3P	99.86	70.58	4354

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 49.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 32)

• downregulation by specific antisense oligonucleotides sensitizes human lung carcinoma cells to treatment with the DNA-damaging agent cisplatin (PMID:11920544)
• Rad9, Hus1, and Rad1 heterotrimeric complex chromatin binding is a proximal event in the checkpoint signaling cascade (PMID:12228248)
• HUS1 is an unstable protein that is actively degraded via the ubiquitin-proteasome pathway. Its expression can be stabilized by treating cells with proteasome-specific inhibitors. (PMID:15122316)
• The human Rad9/Rad1/Hus1 complex interacts with and stimulates DNA polymerase beta activity. (PMID:15314187)
• complex with rad1 and rad9 is a damage-specific activator of flap endonuclease 1 (PMID:15556996)
• The long-patch base excision machinery is an important target of the Rad9-Rad1-Hus1 complex, thus enhancing the quality control of DNA. (PMID:15871698)
• PCNA and the Rad9/Rad1/Hus1 complex can independently bind and activate Fen1; acetylation of Fen1 by p300-HAT abolished the stimulatory effect of the complex but not that of PCNA, suggesting a possible mechanism of regulation of this repair pathway (PMID:16216273)
• human DNA ligase I is stimulated by the Rad9-rad1-Hus1 checkpoint complex (PMID:16731526)
• These data provide in vivo evidence that the human 9-1-1 complex participates in DNA repair in addition to its previously described role in DNA damage sensing. (PMID:16814252)
• Human NEIL1 DNA glycosylase activity is significantly stimulated by Hus1 and by the Rad9/Rad1/Hus1 heterotrimer. (PMID:17395641)
• we report successful tri-cistronic cloning, overexpression and purification of a three-protein complex of Rad9, Rad1 and Hus1 using a single hexa-histidine tag. (PMID:17493829)
• Jab1 physically associates with the 9-1-1 complex (Rad1-Rad9-Hus1) (PMID:17583730)
• Human thymine DNA glycosylase activity is significantly stimulated by hHus1, hRad1, hRad9 separately, and by the 9-1-1 complex. (PMID:17855402)
• Hus1 levels correlated significantly with the clinicopathologic factors of bad prognosis in epithelial ovarian tumors (PMID:18156970)
• Loss of HUS1 sensitizes cells to etopside-induced apoptosis by regulating BH3-only proteins. (PMID:18794804)
• The DNA binding domain (DBD) within the hLigI catalytic fragment interacts with both PCNA and the heterotrimeric cell-cycle checkpoint clamp, hRad9-hRad1-hHus1 (9-1-1). (PMID:19523882)
• The interdomain connecting loops (IDC loop) of hRad9, hHus1, and hRad1 are largely divergent and unique structural features of the 9-1-1 complex that are proposed to contribute to DNA damage recognition. (PMID:19535328)
• Rad9-Rad1-Hus1 complex enhances in vitro activity of 8-oxoguanine DNA glycosylase. (PMID:19615952)
• 9-1-1 complex is a component of the mismatch repair involved in MNNG-induced damage response. (PMID:20188637)
• The HUS1 protein interacts with casein kinase 2. (PMID:20545769)
• The HUS1 is loaded to damaged sites where it serves as a platform for the selective recruitment of checkpoint and repair proteins. (PMID:21978893)
• Data show models for the ternary PCNA/FEN1/DNA and Rad9-Rad1-Hus1 (9-1-1 complex)/FEN1/DNA assemblies. (PMID:22586102)
• HUS1 polymorphisms act as risk breast cancer modifiers in the group of non-carriers of BRCA1/2 mutations. (PMID:22926736)
• Expression of cell cycle regulatory factors hus1, gadd45a, rb1, cdkn2a and mre11a correlates with expression of clock gene per2 in human colorectal carcinoma tissue. (PMID:24062075)
• these pockets were not required for 9-1-1 chromatin localization or ATR-mediated CHK1 activation but were necessary for interactions between HUS1 and its binding partner MYH (PMID:25911100)
• Intramolecular binding of the rad9 C-terminus in the checkpoint clamp Rad9-Hus1-Rad1 is closely linked with its DNA binding. (PMID:26088138)
• adenine glycosylase activity, mismatch recognition properties and interaction with protein partners of MUTYH and 5 MAP variants were examined; P502L and R520Q had reduced affinity for PCNA; only Q324H was found to have reduced affinity for Hus1 (PMID:26377631)
• These results suggest that p21(Waf1/CIP1) and Hus1 play crucial roles in the generation and transmission of bystander damage signals after low-dose alpha-particle irradiation. (PMID:26600172)
• Low HUS1 expression is associated with hepatocellular carcinoma. (PMID:30182378)
• In vivo miRNA knockout screening identifies miR-190b as a novel tumor suppressor. (PMID:33137086)
• MiR-340-3p-HUS1 axis suppresses proliferation and migration in lung adenocarcinoma cells. (PMID:33711383)
• Functional study of the yeast homolog. (PMID:9524127)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000101611
mus_musculus	Hus1	ENSMUSG00000020413
rattus_norvegicus	Hus1	ENSRNOG00000005141
drosophila_melanogaster	Hus1-like	FBGN0026417
caenorhabditis_elegans	hus-1	WBGENE00002042

Paralogs (1): HUS1B (ENSG00000188996)

Protein

Protein identifiers

Checkpoint protein HUS1 — O60921 (reviewed: O60921)

All UniProt accessions (6): A4D2F2, C9JA95, C9JCK8, O60921, F8WAW9, H7C272

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3’-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates. The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase.

Subunit / interactions. Component of the toroidal 9-1-1 (RAD9-RAD1-HUS1) complex, composed of RAD9A, RAD1 and HUS1. The 9-1-1 complex associates with LIG1, POLB, FEN1, RAD17, HDAC1, RPA1 and RPA2. The 9-1-1 complex associates with the RAD17-RFC complex. HUS1 interacts with POLB, HDAC1, FEN1, PCNA and RAD9B. HUS1 does not interact with RAD17. Interacts with DNAJC7.

Subcellular location. Nucleus. Cytoplasm. Cytosol.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the HUS1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60921-1	1	yes
O60921-2	2

RefSeq proteins (2): NP_001350612, NP_004498* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007150	HUS1/Mec3	Family
IPR016580	HUS1	Family
IPR046938	DNA_clamp_sf	Homologous_superfamily

Pfam: PF04005

Enzyme classification (BRENDA):

• EC 2.3.2.27 — RING-type E3 ubiquitin transferase (BRENDA: 28 organisms, 138 substrates, 10 inhibitors, 1 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.3014	1

UniProt features (34 total): strand 22, helix 6, sequence variant 3, chain 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8GNN	X-RAY DIFFRACTION	2.12
6J8Y	X-RAY DIFFRACTION	2.4
3A1J	X-RAY DIFFRACTION	2.5
8WU8	X-RAY DIFFRACTION	2.81
3G65	X-RAY DIFFRACTION	2.9
3GGR	X-RAY DIFFRACTION	3.2
7Z6H	ELECTRON MICROSCOPY	3.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60921-F1	90.20	0.73

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-176187	Activation of ATR in response to replication stress
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-9709570	Impaired BRCA2 binding to RAD51

MSigDB gene sets: 231 (showing top): PID_FANCONI_PATHWAY, GOBP_CHROMOSOME_ORGANIZATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPONSE_TO_IONIZING_RADIATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, PID_TELOMERASE_PATHWAY, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_CELL_CYCLE_PHASE_TRANSITION, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS, GOBP_TELOMERE_ORGANIZATION, KAUFFMANN_DNA_REPAIR_GENES, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, GOBP_MITOTIC_INTRA_S_DNA_DAMAGE_CHECKPOINT_SIGNALING, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_NUCLEOTIDE_EXCISION_REPAIR

GO Biological Process (13): DNA damage checkpoint signaling (GO:0000077), telomere maintenance (GO:0000723), double-strand break repair via homologous recombination (GO:0000724), DNA repair (GO:0006281), nucleotide-excision repair (GO:0006289), DNA damage response (GO:0006974), response to UV (GO:0009411), embryo development ending in birth or egg hatching (GO:0009792), mitotic intra-S DNA damage checkpoint signaling (GO:0031573), mitotic DNA replication checkpoint signaling (GO:0033314), meiotic DNA integrity checkpoint signaling (GO:0044778), cellular response to ionizing radiation (GO:0071479), response to radiation (GO:0009314)

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

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), checkpoint clamp complex (GO:0030896), site of double-strand break (GO:0035861), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
G2/M Checkpoints	2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	2
Homologous DNA Pairing and Strand Exchange	1
Regulation of TP53 Activity	1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA integrity checkpoint signaling	2
DNA metabolic process	2
nuclear lumen	2
signal transduction in response to DNA damage	1
telomere organization	1
recombinational repair	1
double-strand break repair	1
DNA damage response	1
DNA repair	1
cellular response to stress	1
response to light stimulus	1
embryo development	1
mitotic S phase	1
mitotic DNA damage checkpoint signaling	1
DNA replication checkpoint signaling	1
mitotic cell cycle	1
mitotic DNA integrity checkpoint signaling	1
mitotic G2/M transition checkpoint	1
meiotic cell cycle checkpoint signaling	1
meiotic cell cycle	1
response to ionizing radiation	1
cellular response to radiation	1
response to abiotic stimulus	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
condensed nuclear chromosome	1
nuclear protein-containing complex	1
site of DNA damage	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HUS1	RAD9A	Q99638	999
HUS1	RAD17	O75943	993
HUS1	TOPBP1	Q92547	990
HUS1	CLSPN	Q9HAW4	956
HUS1	RAD1	O60671	954
HUS1	ATRIP	Q8WXE1	950
HUS1	CHEK1	O14757	924
HUS1	RAD9B	Q6WBX8	876
HUS1	ATR	Q13535	872
HUS1	ATM	Q13315	852
HUS1	RFC2	P32846	839
HUS1	MUTYH	Q9UIF7	819
HUS1	FEN1	P39748	806
HUS1	XRCC5	P13010	802
HUS1	MDC1	Q14676	778

IntAct

80 interactions, top by confidence:

A	B	Type	Score
HUS1	RAD9A	psi-mi:“MI:0915”(physical association)	0.930
RAD9A	HUS1	psi-mi:“MI:0915”(physical association)	0.930
HUS1	RAD1	psi-mi:“MI:0915”(physical association)	0.840
RAD1	HUS1	psi-mi:“MI:0915”(physical association)	0.840
HUS1	RAD1	psi-mi:“MI:0914”(association)	0.840
ARPC5	ARPC3	psi-mi:“MI:0914”(association)	0.730
RAD9A	RAD1	psi-mi:“MI:0914”(association)	0.670
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
VSIG1	TTI1	psi-mi:“MI:0914”(association)	0.640
HUS1	GRIP1	psi-mi:“MI:0915”(physical association)	0.560
HUS1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
HUS1	DCUN1D5	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	HUS1	psi-mi:“MI:0915”(physical association)	0.560
HUS1	C4orf46	psi-mi:“MI:0915”(physical association)	0.560
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
HUS1	ZBTB14	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
VSIG1	TNPO2	psi-mi:“MI:0914”(association)	0.530

BioGRID (211): HUS1 (Affinity Capture-MS), ZBTB14 (Affinity Capture-MS), RAD17 (Affinity Capture-MS), RAD1 (Affinity Capture-MS), RAD9A (Affinity Capture-MS), HUS1 (Affinity Capture-MS), HUS1 (Affinity Capture-MS), HUS1 (Affinity Capture-MS), HUS1 (Affinity Capture-MS), PCNA (Two-hybrid), RAD1 (Affinity Capture-MS), RAD9A (Affinity Capture-MS), ZBTB14 (Affinity Capture-MS), RAD17 (Affinity Capture-MS), HUS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTR4, A1L1L6, A4IF63, A4II46, A6QNS3, A6QQZ7, D2GXS7, D3ZQG6, F7H9X2, O43929, O54956, O60671, O60921, O82134, O82797, P17070, P22177, P24314, Q00268, Q0VFT9, Q12979, Q2HJF8, Q43124, Q43266, Q5R6Z7, Q5R7X9, Q5SSL4, Q5T2T1, Q5U2Y3, Q6DFV5, Q6NVC5, Q8AVG0, Q8BG51, Q8BQY8, Q8BVD5, Q8IWZ6, Q8IXI2, Q8K2G4, Q8R5L3, Q91W86

Diamond homologs: O60921, Q54NC0, Q8BQY8, Q8K572, Q8NHY5, Q9VN60, P78955

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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
Impaired BRCA2 binding to RAD51	5	46.8×	8e-06
HDR through Single Strand Annealing (SSA)	5	44.4×	8e-06
Presynaptic phase of homologous DNA pairing and strand exchange	5	41.2×	9e-06
G2/M DNA damage checkpoint	7	25.5×	2e-06
Processing of DNA double-strand break ends	6	20.8×	2e-05
Regulation of TP53 Activity through Phosphorylation	5	17.8×	4e-04
RHO GTPase Effectors	5	10.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
DNA damage checkpoint signaling	5	40.8×	3e-05
DNA damage response	10	11.2×	6e-06
DNA repair	7	9.3×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1746 predictions. Top by Δscore:

Variant	Effect	Δscore
7:47967804:A:AC	donor_gain	1.0000
7:47967804:ACTG:A	donor_gain	1.0000
7:47967805:C:CA	donor_gain	1.0000
7:47967805:CTG:C	donor_gain	1.0000
7:47967805:CTGC:C	donor_gain	1.0000
7:47967811:AAGG:A	donor_gain	1.0000
7:47967829:A:AC	donor_gain	1.0000
7:47967830:C:CC	donor_gain	1.0000
7:47967926:C:CC	acceptor_gain	1.0000
7:47975683:CTAAC:C	acceptor_gain	1.0000
7:47975696:CCAA:C	acceptor_gain	1.0000
7:47976728:A:AC	donor_gain	1.0000
7:47976729:C:CC	donor_gain	1.0000
7:47978411:ACT:A	donor_loss	1.0000
7:47978412:CTC:C	donor_loss	1.0000
7:47978413:TCA:T	donor_loss	1.0000
7:47978414:CACC:C	donor_loss	1.0000
7:47978415:A:AC	donor_gain	1.0000
7:47978416:C:CC	donor_gain	1.0000
7:47978416:CCAG:C	donor_gain	1.0000
7:47978589:TTCTC:T	acceptor_gain	1.0000
7:47978591:CTC:C	acceptor_gain	1.0000
7:47978592:TC:T	acceptor_gain	1.0000
7:47978593:CC:C	acceptor_gain	1.0000
7:47978593:CCT:C	acceptor_loss	1.0000
7:47978594:C:CC	acceptor_gain	1.0000
7:47978594:CTA:C	acceptor_loss	1.0000
7:47978595:T:G	acceptor_loss	1.0000
7:47978684:CTCA:C	donor_loss	1.0000
7:47978685:TCACC:T	donor_loss	1.0000

AlphaMissense

1879 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:47979512:A:G	F3S	0.996
7:47969257:A:T	V201D	0.995
7:47978436:A:G	L113P	0.995
7:47979507:C:G	A5P	0.995
7:47969245:A:G	F205S	0.994
7:47978436:A:C	L113R	0.993
7:47979506:G:T	A5D	0.993
7:47979509:C:G	R4P	0.993
7:47967809:A:G	C253R	0.992
7:47969284:A:G	L192S	0.992
7:47969309:C:G	A184P	0.992
7:47978563:C:G	G71R	0.992
7:47969244:A:C	F205L	0.991
7:47969244:A:T	F205L	0.991
7:47969246:A:G	F205L	0.991
7:47978460:A:G	L105P	0.991
7:47978502:G:T	A91D	0.991
7:47978774:A:G	L32P	0.991
7:47978430:A:T	V115D	0.990
7:47979511:A:C	F3L	0.990
7:47979511:A:T	F3L	0.990
7:47979513:A:G	F3L	0.990
7:47969308:G:T	A184E	0.989
7:47978436:A:T	L113H	0.989
7:47967844:A:G	L241P	0.988
7:47976804:G:C	H131D	0.988
7:47978538:A:C	I79S	0.988
7:47965384:A:G	L272P	0.987
7:47975614:A:G	L180P	0.987
7:47978538:A:G	I79T	0.987

dbSNP variants (sampled 300 via entrez): RS1000412988 (7:47979290 C>A), RS1000510766 (7:47975335 A>G), RS1000576176 (7:47980676 A>C), RS1000866370 (7:47969655 G>A,C), RS1000997752 (7:47963784 T>C), RS1001261610 (7:47963912 A>C), RS1001340563 (7:47974768 T>C), RS1001855793 (7:47980494 C>G,T), RS1001883004 (7:47976673 A>G), RS1002528962 (7:47967660 T>A), RS1002631295 (7:47968941 G>A,C), RS1002935359 (7:47977560 C>T), RS1003012138 (7:47973445 T>A,C), RS1003110059 (7:47973226 A>G), RS1003125882 (7:47979379 C>A,T)

Disease associations

OMIM: gene MIM:603760 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005050_3	Obstructive sleep apnea during REM sleep (apnea hypopnea index)	8.000000e-07
GCST010817_4	Gut microbiota alpha diversity (Shannon index)	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008455	sleep apnea measurement during REM sleep
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1056663	HUS1		0.00	0
rs2037483	HUS1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	decreases expression, decreases response to substance, increases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
myristicin	decreases expression	1
triphenyl phosphate	affects expression	1
Nonidet P-40	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
cupric oxide	increases expression	1
1-hydroxypyrene	affects cotreatment, decreases methylation	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
riccardin D	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Phenobarbital	affects expression	1
Rotenone	increases expression	1
Theophylline	decreases expression	1
Urethane	increases expression	1
Isotretinoin	decreases expression	1
Metribolone	increases expression	1

Clinical trials (associated diseases)

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