ASCC2

Summary

ASCC2 (activating signal cointegrator 1 complex subunit 2, HGNC:24103) is a protein-coding gene on chromosome 22q12.2, encoding Activating signal cointegrator 1 complex subunit 2 (Q9H1I8). Ubiquitin-binding protein involved in DNA repair and rescue of stalled ribosomes.

Enables K63-linked polyubiquitin modification-dependent protein binding activity. Involved in regulation of DNA-templated transcription; rescue of stalled cytosolic ribosome; and ribosome-associated ubiquitin-dependent protein catabolic process. Located in nucleus. Part of RQC-trigger complex. Is active in cytosolic ribosome.

Source: NCBI Gene 84164 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 133 total
• GTEx eGene: eQTL in 38 tissues, sQTL in 22 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.59 (moderately constrained)
• MANE Select transcript: NM_032204
• Notable: 133 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24103
Approved symbol	ASCC2
Name	activating signal cointegrator 1 complex subunit 2
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	ASC1p100, FLJ21588, DKFZp586O0223
Ensembl gene	ENSG00000100325
Ensembl biotype	protein_coding
OMIM	614216
Entrez	84164

Gene structure

Transcript identifiers

Ensembl transcripts: 111 — 65 protein_coding, 31 nonsense_mediated_decay, 8 retained_intron, 7 protein_coding_CDS_not_defined

MANE Select: ENST00000307790

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 5, TSL 3: 6, TSL 4: 5, TSL 5: 6

ENST00000307790, ENST00000397771, ENST00000411532, ENST00000412689, ENST00000431535, ENST00000449900, ENST00000453160, ENST00000454854, ENST00000458594, ENST00000460313, ENST00000462454, ENST00000463203, ENST00000464287, ENST00000465667, ENST00000472433, ENST00000477074, ENST00000478812, ENST00000483380, ENST00000487486, ENST00000492821, ENST00000495681, ENST00000495967, ENST00000542393, ENST00000865563, ENST00000865564, ENST00000865565, ENST00000865566, ENST00000865567, ENST00000865568, ENST00000865569, ENST00000865570, ENST00000865571, ENST00000865572, ENST00000865573, ENST00000865574, ENST00000865575, ENST00000865576, ENST00000865577, ENST00000865578, ENST00000865579, ENST00000865580, ENST00000865581, ENST00000865582, ENST00000865583, ENST00000865584, ENST00000865585, ENST00000865586, ENST00000865587, ENST00000865588, ENST00000865589, ENST00000865590, ENST00000865591, ENST00000865592, ENST00000923277, ENST00000923278, ENST00000923279, ENST00000923280, ENST00000923281, ENST00000923282, ENST00000923283, ENST00000923284, ENST00000923285, ENST00000923286, ENST00000923287, ENST00000923288, ENST00000923289, ENST00000960640, ENST00000960641, ENST00000960642, ENST00000960643, ENST00000960644, ENST00000960645, ENST00000960646, ENST00000960647, ENST00000960648, ENST00000960649, ENST00000960650, ENST00000960651, ENST00001001253, ENST00001001254, ENST00001001255, ENST00001001256, ENST00001001257, ENST00001001258, ENST00001001259, ENST00001001260, ENST00001047745, ENST00001047746, ENST00001047747, ENST00001047748, ENST00001047749, ENST00001047750, ENST00001047751, ENST00001047752, ENST00001047753, ENST00001047754, ENST00001047755, ENST00001047757, ENST00001047758, ENST00001047759, ENST00001047760, ENST00001084734, ENST00001084735, ENST00001084736, ENST00001084737, ENST00001111319, ENST00001111320, ENST00001111321, ENST00001114357, ENST00001114358, ENST00001131640

RefSeq mRNA: 33 — MANE Select: NM_032204 NM_001242906, NM_001369920, NM_001369921, NM_001369922, NM_001369923, NM_001369924, NM_001369925, NM_001369926, NM_001369927, NM_001369928, NM_001369929, NM_001369930, NM_001369931, NM_001369932, NM_001369933, NM_001369934, NM_001369935, NM_001369936, NM_001369937, NM_001369938, NM_001369939, NM_001369940, NM_001369941, NM_001369942, NM_001369943, NM_001369944, NM_001369945, NM_001369946, NM_001369947, NM_001369948, NM_001369949, NM_001369950, NM_032204

CCDS: CCDS13869, CCDS56226

Canonical transcript exons

ENST00000307790 — 20 exons

Exon	Start	End
ENSE00001736534	29838178	29838274
ENSE00001889854	29788611	29789184
ENSE00003469822	29816006	29816073
ENSE00003487030	29806797	29806904
ENSE00003501666	29806216	29806290
ENSE00003510185	29800991	29801110
ENSE00003512180	29790469	29790548
ENSE00003535549	29793360	29793490
ENSE00003553125	29804638	29804830
ENSE00003557333	29832245	29832342
ENSE00003564625	29822335	29822464
ENSE00003572205	29792433	29792535
ENSE00003587779	29801994	29802208
ENSE00003617950	29825087	29825257
ENSE00003665332	29825622	29825780
ENSE00003666115	29813430	29813542
ENSE00003668371	29808111	29808185
ENSE00003690080	29806485	29806553
ENSE00003786924	29793577	29793676
ENSE00003789123	29814657	29814767

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.2481 / max 1255.1986, expressed in 1819 samples.

Highest expression (Bgee): lower esophagus mucosa, esophagus mucosa, granulocyte, blood, minor salivary gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ASCC2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 38 tissues and its splicing (sQTL) in 22 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 60 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	7.1e-45	+0.48	22:29838056:G:A
Skin Sun Exposed Lower leg	sqtl	9.9e-43	+0.69	22:29807610:C:G
Skin Not Sun Exposed Suprapubic	sqtl	1.9e-28	+0.61	22:29775042:T:G
Adipose Subcutaneous	sqtl	5.3e-20	-0.57	22:29788961:A:G
Esophagus Mucosa	sqtl	4.0e-18	-0.56	22:29788961:A:G
Testis	sqtl	1.7e-16	+0.54	22:29815887:A:G
Thyroid	sqtl	1.2e-15	-0.48	22:29792256:T:G
Adipose Visceral Omentum	sqtl	1.2e-15	-0.55	22:29788961:A:G
Artery Aorta	eqtl	3.8e-14	+0.49	22:29838229:A:T
Breast Mammary Tissue	sqtl	7.5e-14	-0.57	22:29788961:A:G
Thyroid	eqtl	2.8e-13	+0.39	22:29786353:C:T
Esophagus Muscularis	eqtl	7.7e-13	+0.48	22:29803642:C:T
Nerve Tibial	eqtl	1.6e-12	+0.42	22:29803642:C:T
Brain Spinal cord cervical c-1	eqtl	1.6e-12	+0.72	22:29739090:C:T
Brain Cerebellar Hemisphere	eqtl	2.3e-12	+0.51	22:29809948:G:A
Artery Tibial	eqtl	3.3e-12	+0.34	22:29805392:C:T
Pituitary	eqtl	4.9e-12	+0.51	22:29838229:A:T
Muscle Skeletal	eqtl	1.5e-11	+0.26	22:29739090:C:T
Whole Blood	sqtl	4.1e-11	+1.28	22:29734642:C:CT
Lung	sqtl	4.4e-11	-0.48	22:29788961:A:G

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
193558	33.6612	1818
193554	0.3314	150
193557	0.1214	46
193556	0.0668	20
193555	0.0593	20
193553	0.0080	3

Top tissues by expression

showing 100 of 293 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.61	gold quality
esophagus mucosa	UBERON:0002469	95.83	gold quality
granulocyte	CL:0000094	95.66	gold quality
blood	UBERON:0000178	95.52	gold quality
minor salivary gland	UBERON:0001830	95.15	gold quality
right lobe of thyroid gland	UBERON:0001119	95.04	gold quality
right lobe of liver	UBERON:0001114	94.71	gold quality
left lobe of thyroid gland	UBERON:0001120	94.65	gold quality
mucosa of transverse colon	UBERON:0004991	94.61	gold quality
body of stomach	UBERON:0001161	94.58	gold quality
left adrenal gland cortex	UBERON:0035825	94.51	gold quality
left adrenal gland	UBERON:0001234	94.41	gold quality
right adrenal gland	UBERON:0001233	94.36	gold quality
skin of abdomen	UBERON:0001416	94.36	gold quality
skin of leg	UBERON:0001511	94.33	gold quality
monocyte	CL:0000576	94.30	gold quality
right adrenal gland cortex	UBERON:0035827	94.29	gold quality
mouth mucosa	UBERON:0003729	94.28	gold quality
mononuclear cell	CL:0000842	94.20	gold quality
leukocyte	CL:0000738	94.13	gold quality
adenohypophysis	UBERON:0002196	94.06	gold quality
saliva-secreting gland	UBERON:0001044	94.03	gold quality
thyroid gland	UBERON:0002046	93.87	gold quality
right uterine tube	UBERON:0001302	93.71	gold quality
adrenal cortex	UBERON:0001235	93.69	gold quality
stomach	UBERON:0000945	93.64	gold quality
adrenal gland	UBERON:0002369	93.50	gold quality
sural nerve	UBERON:0015488	93.47	gold quality
esophagus	UBERON:0001043	93.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.36	gold quality
rectum	UBERON:0001052	93.34	gold quality
omental fat pad	UBERON:0010414	93.24	gold quality
peritoneum	UBERON:0002358	93.21	gold quality
body of pancreas	UBERON:0001150	93.18	gold quality
transverse colon	UBERON:0001157	93.07	gold quality
gastrocnemius	UBERON:0001388	93.06	gold quality
left testis	UBERON:0004533	93.04	gold quality
ectocervix	UBERON:0012249	92.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.92	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.90	gold quality
muscle of leg	UBERON:0001383	92.78	gold quality
upper lobe of left lung	UBERON:0008952	92.71	gold quality
right testis	UBERON:0004534	92.67	gold quality
pituitary gland	UBERON:0000007	92.66	gold quality
apex of heart	UBERON:0002098	92.57	gold quality
spleen	UBERON:0002106	92.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.31	gold quality
right atrium auricular region	UBERON:0006631	92.15	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.12	gold quality
metanephros cortex	UBERON:0010533	92.05	gold quality
nerve	UBERON:0001021	92.02	gold quality
tibial nerve	UBERON:0001323	92.02	gold quality
small intestine	UBERON:0002108	91.86	gold quality
body of uterus	UBERON:0009853	91.85	gold quality
left uterine tube	UBERON:0001303	91.83	gold quality
decidua	UBERON:0002450	91.83	gold quality
gall bladder	UBERON:0002110	91.79	gold quality
upper lobe of lung	UBERON:0008948	91.70	gold quality
buccal mucosa cell	CL:0002336	91.64	gold quality
right ovary	UBERON:0002118	91.52	gold quality
colonic epithelium	UBERON:0000397	91.51	gold quality
zone of skin	UBERON:0000014	91.50	gold quality
right lung	UBERON:0002167	91.50	gold quality
endocervix	UBERON:0000458	91.46	gold quality
bone marrow	UBERON:0002371	91.41	gold quality
tendon of biceps brachii	UBERON:0008188	91.41	gold quality
pancreas	UBERON:0001264	91.37	gold quality
right coronary artery	UBERON:0001625	91.31	gold quality
bone marrow cell	CL:0002092	91.29	gold quality
tonsil	UBERON:0002372	91.28	gold quality
testis	UBERON:0000473	91.27	gold quality
vagina	UBERON:0000996	91.20	gold quality
islet of Langerhans	UBERON:0000006	91.18	gold quality
left ovary	UBERON:0002119	91.12	gold quality
fundus of stomach	UBERON:0001160	91.09	gold quality
left coronary artery	UBERON:0001626	91.04	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.98	gold quality
heart left ventricle	UBERON:0002084	90.91	gold quality
cardiac atrium	UBERON:0002081	90.85	gold quality
stromal cell of endometrium	CL:0002255	90.83	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.83	gold quality
lower esophagus	UBERON:0013473	90.74	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.72	gold quality
coronary artery	UBERON:0001621	90.70	gold quality
adipose tissue	UBERON:0001013	90.68	gold quality
ganglionic eminence	UBERON:0004023	90.65	gold quality
ascending aorta	UBERON:0001496	90.63	gold quality
thoracic aorta	UBERON:0001515	90.58	gold quality
muscle organ	UBERON:0001630	90.51	gold quality
cardiac ventricle	UBERON:0002082	90.48	gold quality
connective tissue	UBERON:0002384	90.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.41	gold quality
intestine	UBERON:0000160	90.36	gold quality
descending thoracic aorta	UBERON:0002345	90.28	gold quality
colon	UBERON:0001155	90.22	gold quality
heart	UBERON:0000948	90.11	gold quality
aorta	UBERON:0000947	90.04	gold quality
urinary bladder	UBERON:0001255	90.02	gold quality
lymph node	UBERON:0000029	89.99	gold quality
pharyngeal mucosa	UBERON:0000355	89.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	50.7
Stomach 1	tissue	34.9	high
Esophagus	tissue	34.4	high
Tonsil	tissue	31.8	high
Skeletal muscle	tissue	31.0	medium
Tongue	tissue	30.1
Thymus	tissue	27.6
Skin 1	tissue	27.4	high
Liver	tissue	27.3	medium
Vagina	tissue	26.0	medium
Urinary bladder	tissue	25.1	high
Adrenal gland	tissue	25.0	medium
Salivary gland	tissue	24.7	medium
Pituitary gland	tissue	24.6
Adipose tissue	tissue	24.5	low
Choroid plexus	tissue	23.9
Rectum	tissue	23.1	high
Spleen	tissue	23.0	medium
Lymph node	tissue	22.9	high
Testis	tissue	22.9	medium
Colon	tissue	22.9	high
Duodenum	tissue	22.3	high
Pancreas	tissue	21.7	high
Small intestine	tissue	21.5	high
Appendix	tissue	21.4	high
Thyroid gland	tissue	20.9	high
Parathyroid gland	tissue	20.5
Placenta	tissue	20.5	high
Lung	tissue	18.7	high
Fallopian tube	tissue	18.7	high
Prostate	tissue	18.5	medium
Smooth muscle	tissue	18.0	medium
Heart muscle	tissue	17.7	medium
Cervix	tissue	17.5	medium
Seminal vesicle	tissue	17.0	high
Ovary	tissue	16.2	medium
Gallbladder	tissue	16.0	high
Breast	tissue	15.8	high
Epididymis	tissue	15.2	high
Endometrium 1	tissue	14.7	high
Kidney	tissue	13.7	high
Locus coeruleus	tissue	13.1
Hippocampus	tissue	13.0	not detected
Spinal cord	tissue	11.8
Corpus callosum	tissue	11.3
Nucleus accumbens	tissue	11.0
Cerebellum	tissue	10.8
Midbrain	tissue	10.7
Superior colliculi	tissue	10.7
Substantia nigra	tissue	10.7
Hippocampal formation	tissue	10.7
Ventral forebrain	tissue	10.7
Septum	tissue	10.7
Medulla oblongata	tissue	10.4
Cerebral cortex	tissue	10.3	medium
Motor cortex	tissue	10.3
Putamen	tissue	10.3
Insular cortex	tissue	10.3
Somatosensory cortex	tissue	10.2
Retrosplenial cortex	tissue	10.2

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (19.2), Nucleus gracilis (17.1), Dorsal tegmental nucleus (16.9), Area postrema (16.8), Lateral vestibular nucleus (16.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

Targeting ASCC2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 31 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-1226-5P	96.50	65.28	643
HSA-MIR-7108-5P	96.42	66.17	598
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-6834-5P	96.25	64.88	823
HSA-MIR-1178-5P	95.83	64.12	504
HSA-MIR-6734-5P	95.70	65.56	950

Functional genomics

gnomAD constraint: pLI 0.00196, LOEUF 0.593, missense Z 1.6 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000307790 — one region, missense o/e 0.88.

Literature-anchored findings (GeneRIF, showing 2)

• The interaction of DNA repair factors ASCC2 and ASCC3 is affected by somatic cancer mutations. (PMID:33139697)
• Identification of key genes in coronary artery disease: an integrative approach based on weighted gene co-expression network analysis and their correlation with immune infiltration. (PMID:33686958)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ascc2	ENSDARG00000013058
mus_musculus	Ascc2	ENSMUSG00000020412
rattus_norvegicus	Ascc2	ENSRNOG00000007349
drosophila_melanogaster	CG2701	FBGN0024973

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1922702) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
enlarged spleen	1
trunk curl	1
increased circulating chloride level	1
decreased heart left ventricle size	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	1

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
HORMAD2-AS1	ncRNA	101929664
MIR6818	ncRNA	102466742
MTMR3	protein-coding	8897
UQCR10	protein-coding	29796
CABP7	protein-coding	164633
ZMAT5	protein-coding	55954
CABP7-DT	ncRNA	122149303
NF2	protein-coding	4771
HORMAD2	protein-coding	150280

Protein

Protein identifiers

Activating signal cointegrator 1 complex subunit 2 — Q9H1I8 (reviewed: Q9H1I8)

Alternative names: ASC-1 complex subunit p100, Trip4 complex subunit p100

All UniProt accessions (5): B1AH59, Q9H1I8, F2Z2W4, H7C395, H7C3Y4

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-binding protein involved in DNA repair and rescue of stalled ribosomes. Plays a role in DNA damage repair as component of the ASCC complex. Recruits ASCC3 and ALKBH3 to sites of DNA damage by binding to polyubiquitinated proteins that have ‘Lys-63’-linked polyubiquitin chains. Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation. Involved in activation of the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation. Specifically recognizes and binds RPS20/uS10 ubiquitinated by ZNF598, promoting recruitment of the RQT (ribosome quality control trigger) complex on stalled ribosomes, followed by disassembly of stalled ribosomes.

Subunit / interactions. Identified in the ASCC complex that contains ASCC1, ASCC2 and ASCC3. Interacts directly with ASCC3. The ASCC complex interacts with ALKBH3. Interacts (via CUE domain) with ‘Lys-63’-linked polyubiquitin chains, but not with ‘Lys-48’-linked polyubiquitin chains. Part of the ASC-1 complex, that contains TRIP4, ASCC1, ASCC2 and ASCC3. Component of the RQT (ribosome quality control trigger) complex, that contains ASCC2, ASCC3 and TRIP4. Interacts with CSRP1. Interacts with PRPF8, a component of the spliceosome. Interacts with ZCCHC4.

Subcellular location. Nucleus. Nucleus speckle.

Tissue specificity. Ubiquitous.

Domain organisation. The CUE domain specifically binds RPS20/uS10 ubiquitinated via ‘Lys-63’-linked ubiquitin chains by ZNF598.

Similarity. Belongs to the ASCC2 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H1I8-1	1	yes
Q9H1I8-2	2
Q9H1I8-3	3

RefSeq proteins (33): NP_001229835, NP_001356849, NP_001356850, NP_001356851, NP_001356852, NP_001356853, NP_001356854, NP_001356855, NP_001356856, NP_001356857, NP_001356858, NP_001356859, NP_001356860, NP_001356861, NP_001356862, NP_001356863, NP_001356864, NP_001356865, NP_001356866, NP_001356867, NP_001356868, NP_001356869, NP_001356870, NP_001356871, NP_001356872, NP_001356873, NP_001356874, NP_001356875, NP_001356876, NP_001356877, NP_001356878, NP_001356879, NP_115580* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003892	CUE	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR041800	ASCC2-like_CUE	Domain
IPR052586	ASCC2	Family

Pfam: PF02845

UniProt features (73 total): helix 29, sequence variant 8, sequence conflict 8, turn 6, splice variant 5, modified residue 4, mutagenesis site 3, strand 3, compositionally biased region 3, region of interest 2, chain 1, domain 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
6YXQ	Crystal structure of a DNA repair complex ASCC3-ASCC2	X-RAY DIFFRACTION	2.7
2DI0	Solution Structure of the CUE Domain in the Human Activating Signal Cointegrator 1 …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1I8-F1	78.15	0.45

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; focal adhesion sites; nucleoplasm

Antibody reliability (HPA): IH approved · IF approved

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)

Type	Positions
Phosphoserine	713, 447, 632
Phosphothreonine	233

Mutagenesis-validated functional residues (3)

Position	Phenotype
478–479	loss of ubiquitin binding.
479–491	decreases ubiquitin binding.
506	loss of ubiquitin binding.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-112126	ALKBH3 mediated reversal of alkylation damage	curated
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	curated
R-HSA-73942	DNA Damage Reversal	—
R-HSA-73894	DNA Repair	—
R-HSA-73943	Reversal of alkylation damage by DNA dioxygenases	—

MSigDB gene sets: 128 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_TRANSLATION, GTGCCTT_MIR506, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GROSS_HYPOXIA_VIA_ELK3_DN, GROSS_HYPOXIA_VIA_ELK3_ONLY_UP, GOBP_DNA_DAMAGE_RESPONSE, GOBP_TRANSLATIONAL_ELONGATION, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, REACTOME_DNA_REPAIR, MODULE_60, TGCCTTA_MIR124A, GOBP_DNA_REPLICATION, GOBP_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (9): DNA replication (GO:0006260), DNA alkylation repair (GO:0006307), DNA-templated transcription (GO:0006351), regulation of DNA-templated transcription (GO:0006355), ribosome disassembly (GO:0032790), rescue of stalled cytosolic ribosome (GO:0072344), ribosome-associated ubiquitin-dependent protein catabolic process (GO:1990116), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (3): ubiquitin binding (GO:0043130), K63-linked polyubiquitin modification-dependent protein binding (GO:0070530), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear speck (GO:0016607), cytosolic ribosome (GO:0022626), RQC-trigger complex (GO:0180022)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Reversal of alkylation damage by DNA dioxygenases	1
Ribosome-associated quality control	1
DNA Repair	1
DNA Damage Reversal	1

GO top-level categories

25 GO namespaces:

Category	Terms
DNA metabolic process	2
cellular anatomical structure	2
DNA biosynthetic process	1
DNA repair	1
gene expression	1
RNA biosynthetic process	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
organelle disassembly	1
cytoplasmic translational elongation	1
ribosome disassembly	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
DNA damage response	1
cellular response to stress	1
ubiquitin-like protein binding	1
polyubiquitin modification-dependent protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
cytosol	1
ribosome	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
regulation of DNA-templated transcription	BP	direct assay
rescue of stalled cytosolic ribosome	BP	direct assay
ribosome disassembly	BP	direct assay
ribosome-associated ubiquitin-dependent protein catabolic process	BP	mutant phenotype
RQC-trigger complex	CC	direct assay
cytosolic ribosome	CC	direct assay
nucleus	CC	direct assay
K63-linked polyubiquitin modification-dependent protein binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,172 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASCC2	ASCC1	Q8N9N2	840
ASCC2	ASCC3	Q8N3C0	836
ASCC2	TRIP4	Q15650	813
ASCC2	ZNF598	Q86UK7	741
ASCC2	RNF113A	O15541	697
ASCC2	ZMAT5	Q9UDW3	602
ASCC2	GAS2L1	Q99501	591
ASCC2	NEMF	O60524	577
ASCC2	LRRC18	Q8N456	546
ASCC2	PELO	Q9BRX2	534
ASCC2	RASL10A	Q92737	524
ASCC2	RPS20	P17075	523
ASCC2	LTN1	O94822	511
ASCC2	ALKBH3	Q96Q83	499
ASCC2	LRRC46	Q96FV0	473

IntAct

Human interaction partners of ASCC2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 41 partners by confidence:

Partner	Interaction type	MIscore	Records
ASCC3	physical association	0.790	6
TRIP4	association	0.640	2
KATNAL1	physical association	0.560	3
PRPF18	physical association	0.560	3
ENTREP1	physical association	0.370	1
GADD45A	physical association	0.370	1
PCBD2	physical association	0.370	1
RNF11	physical association	0.370	1
AMY1A	association	0.350	1
ASS1	physical association	0.000	1
CKAP4	physical association	0.000	1
CUTC	physical association	0.000	1
DEAF1	physical association	0.000	1
EEF1D	physical association	0.000	1
ELAC2	physical association	0.000	1
FAF1	physical association	0.000	1
FBP1	physical association	0.000	1
FLJ10324	physical association	0.000	1
FUNDC2	physical association	0.000	1
GFER	physical association	0.000	1
GNL3	physical association	0.000	1
GTF3C1	physical association	0.000	1
IGSF9	physical association	0.000	1
IMMT	physical association	0.000	1
KDM1A	physical association	0.000	1
LPL	physical association	0.000	1
MED31	physical association	0.000	1
MYH9	physical association	0.000	1
OLA1	physical association	0.000	1
PIK3CD	physical association	0.000	1

BioGRID (164 interactions; top human partners by supporting records): ASCC3 (Co-fractionation; 10 records), TRIP4 (Co-fractionation; 9 records), ASCC1 (Affinity Capture-MS; 8 records), UBC (Reconstituted Complex; 4 records), ALKBH3 (Affinity Capture-MS; 3 records), DNAJA2 (Proximity Label-MS; 2 records), FMR1 (Affinity Capture-Western; 2 records), SASH1 (Two-hybrid; 2 records), ABT1 (Affinity Capture-MS), AMY1C (Affinity Capture-MS), ANLN (Affinity Capture-MS), ASS1 (Two-hybrid), BAG2 (Affinity Capture-MS), BAG6 (Affinity Capture-MS), BRD7 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
SMURF1	unknown	ASCC2	ubiquitination

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
hASC-1 complex	4	ASCC2, ASCC3, TRIP4, ASCC1

Disease & clinical

Genetic variants

Variant evidence for ASCC2: 133 ClinVar records (0 pathogenic / likely pathogenic); 14 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	4
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 1,985):

Position(s)	Effect	Δscore	Sites
22:29790467–29790468	donor_loss	1.0000	4
22:29790549–29790550	acceptor_loss	1.0000	5
22:29790551	acceptor_gain	1.0000
22:29792431–29792432	donor_loss	1.0000	5
22:29792542	acceptor_gain	1.0000
22:29793358–29793359	donor_loss	1.0000	5
22:29793491–29793492	acceptor_loss	1.0000	4
22:29793575–29793576	donor_loss	1.0000	3
22:29793677–29793678	acceptor_loss	1.0000	6
22:29793689	acceptor_gain	1.0000

AlphaMissense

1,401 missense substitutions predicted likely pathogenic (of 5,025 scored), across 380 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M754	9	0.895	0.991
D193	8	0.953	0.972
F678	8	0.953	0.996
D251	8	0.948	0.981
D163	8	0.940	0.973
F77	8	0.930	0.994
D618	8	0.930	0.971
D157	8	0.928	0.964
D388	8	0.927	0.975
F642	8	0.919	0.992
D617	8	0.916	0.966
D614	8	0.912	0.978
D681	8	0.904	0.983
D546	8	0.903	0.947
H740	8	0.899	0.987
D65	8	0.893	0.952
F124	8	0.889	0.974
D376	8	0.853	0.948
D629	8	0.850	0.948
F363	8	0.842	0.981

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:614216 | disease phenotypes:

GWAS associations

14 associations:

Study	Trait	p-value
GCST004628_101	Immature fraction of reticulocytes	2e-18
GCST007516_32	Type 2 diabetes (adjusted for BMI)	4e-14
GCST007518_34	Type 2 diabetes (adjusted for BMI)	1e-12
GCST009379_28	Type 2 diabetes	1e-12
GCST90002391_251	Mean corpuscular hemoglobin concentration	8e-11
GCST008568_3	IgA levels	3e-10
GCST003974_1	Tonsillectomy	1e-9
GCST010002_380	Refractive error	2e-9
GCST010083_266	Hemoglobin levels	8e-9
GCST90016667_8	Spleen volume	2e-8
GCST004131_67	Inflammatory bowel disease	4e-8
GCST004001_6	Bipolar disorder or attention deficit hyperactivity disorder	6e-7
GCST004132_71	Crohn’s disease	8e-7
GCST002336_2	Telomere length	9e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0007924	tonsillectomy risk measurement
EFO:0007986	reticulocyte count
EFO:0004509	hemoglobin measurement
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Valproic Acid	affects expression, increases expression	3
bisphenol A	increases expression, affects cotreatment, increases methylation, decreases methylation	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Cyclosporine	increases expression	1
Particulate Matter	increases abundance, increases 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_B1K4	Abcam HeLa ASCC2 KO	Cancer cell line	Female
CVCL_D9XX	Ubigene HeLa ASCC2 KO	Cancer cell line	Female
CVCL_SD58	HAP1 ASCC2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.