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 ribosome; and ribosome-associated ubiquitin-dependent protein catabolic process. Located in nucleus. Part of DNA repair complex and RQC-trigger complex. Is active in cytosolic ribosome.

Source: NCBI Gene 84164 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 133 total
• MANE Select transcript: NM_032204

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: 78 — 60 protein_coding, 8 retained_intron, 7 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

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

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.

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

293 total, 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

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

31 targeting ASCC2, 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-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

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

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): Q9H1I8, B1AH59, 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_CUE	Domain
IPR052586	ASCC2	Family

Pfam: PF02845

UniProt features (68 total): helix 24, 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.

PDB	Method	Resolution (Å)
6YXQ	X-RAY DIFFRACTION	2.7
2DI0	SOLUTION NMR

Predicted structure (AlphaFold)

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

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): 713, 233, 447, 632

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

5 pathways

ID	Pathway
R-HSA-112126	ALKBH3 mediated reversal of alkylation damage
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA
R-HSA-73894	DNA Repair
R-HSA-73942	DNA Damage Reversal
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 (8): DNA replication (GO:0006260), DNA alkylation repair (GO:0006307), 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), nuclear speck (GO:0016607), cytosolic ribosome (GO:0022626), RQC-trigger complex (GO:0180022), DNA repair complex (GO:1990391)

Reactome top-level categories

Rollup of top-4 pathways:

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

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
DNA biosynthetic process	1
DNA repair	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
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1
cytosol	1
ribosome	1
protein-containing complex	1
catalytic complex	1

Protein interactions and networks

STRING

1022 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASCC2	ASCC1	Q8N9N2	988
ASCC2	ASCC3	Q8N3C0	986
ASCC2	TRIP4	Q15650	969
ASCC2	ZNF598	Q86UK7	715
ASCC2	NEMF	O60524	625
ASCC2	GAS2L1	Q99501	601
ASCC2	PELO	Q9BRX2	539
ASCC2	RNF113A	O15541	533
ASCC2	RPS20	P17075	518
ASCC2	ALKBH3	Q96Q83	505
ASCC2	ANKZF1	Q9H8Y5	498
ASCC2	LTN1	O94822	482
ASCC2	ZNF830	Q96NB3	474
ASCC2	XAB2	Q9HCS7	462
ASCC2	TMEM179B	Q7Z7N9	460

IntAct

117 interactions, top by confidence:

A	B	Type	Score
SPC24	NDC80	psi-mi:“MI:0914”(association)	0.920
ASCC2	ASCC3	psi-mi:“MI:0915”(physical association)	0.790
ASCC2	ASCC3	psi-mi:“MI:0407”(direct interaction)	0.790
ASCC2	ASCC3	psi-mi:“MI:0403”(colocalization)	0.790
ASCC3	ASCC2	psi-mi:“MI:0915”(physical association)	0.790
ASCC1	ASCC3	psi-mi:“MI:0914”(association)	0.690
ASCC2	TRIP4	psi-mi:“MI:0914”(association)	0.640
PRPF18	ASCC2	psi-mi:“MI:0915”(physical association)	0.560
KATNAL1	ASCC2	psi-mi:“MI:0915”(physical association)	0.560
ALKBH3	INPPL1	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
TRIP4	ASCC3	psi-mi:“MI:0914”(association)	0.530
ALKBH3	TRIP4	psi-mi:“MI:0914”(association)	0.530
ASCC1	TRIP4	psi-mi:“MI:0914”(association)	0.530
CC2D2A	OFD1	psi-mi:“MI:2364”(proximity)	0.420
PCBD2	ASCC2	psi-mi:“MI:0915”(physical association)	0.370
ASCC2	ENTREP1	psi-mi:“MI:0915”(physical association)	0.370
ASCC2	GADD45A	psi-mi:“MI:0915”(physical association)	0.370
RNF11	ASCC2	psi-mi:“MI:0915”(physical association)	0.370
Bub1	PEX10	psi-mi:“MI:0914”(association)	0.350
Gspt1	MRPL27	psi-mi:“MI:0914”(association)	0.350
PAPD5	UNC119B	psi-mi:“MI:0914”(association)	0.350
EMC2	TBL2	psi-mi:“MI:0914”(association)	0.350
HDAC1	TRAK1	psi-mi:“MI:0914”(association)	0.350

BioGRID (158): ASCC2 (Biochemical Activity), ASCC2 (Affinity Capture-MS), ASCC2 (Affinity Capture-MS), ASCC2 (Co-fractionation), ASCC3 (Co-fractionation), GPC4 (Co-fractionation), TRIP4 (Co-fractionation), ASCC2 (Affinity Capture-MS), ASCC2 (Proximity Label-MS), ASCC2 (Proximity Label-MS), ASCC2 (Affinity Capture-MS), ASCC2 (Affinity Capture-MS), ASCC2 (Affinity Capture-MS), ASCC2 (Affinity Capture-MS), ASCC2 (Affinity Capture-MS)

ESM2 similar proteins: A0A5F9C6I2, A1L3F5, A2BDA5, A3KGS3, A8E4X8, D3ZXK7, F1R7R1, O75129, P21359, P51593, P97526, Q04690, Q1JPG0, Q2PPJ7, Q3SZD5, Q4QQM5, Q4R5A4, Q5RC14, Q5XPI3, Q5XPI4, Q62717, Q66K64, Q6GLR7, Q6NXD8, Q6P4S8, Q6PFH3, Q6VNB8, Q7L4E1, Q7TMY8, Q7Z6Z7, Q80TJ1, Q86UW7, Q8BHR8, Q8BK03, Q8BYR5, Q8CDG3, Q8CF97, Q8CID0, Q8IY22, Q8IZQ1

Diamond homologs: Q91WR3, Q9H1I8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SMURF1	unknown	ASCC2	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 129 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
Eukaryotic Translation Elongation	9	30.6×	4e-09
Eukaryotic Translation Initiation	8	30.1×	1e-08
Cap-dependent Translation Initiation	8	30.1×	1e-08
SARS-CoV-1 modulates host translation machinery	8	30.1×	1e-08
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	8	26.5×	3e-08
SARS-CoV-2 modulates host translation machinery	9	24.6×	1e-08
Nonsense-Mediated Decay (NMD)	8	22.7×	7e-08
Influenza Viral RNA Transcription and Replication	8	21.0×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	11	17.9×	2e-08
ribosomal small subunit biogenesis	8	16.0×	2e-05
translation	9	8.1×	5e-04

Disease & clinical

Clinical variants and AI predictions

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

3781 predictions. Top by Δscore:

Variant	Effect	Δscore
22:29790463:GCTCA:G	donor_loss	1.0000
22:29790464:CTCA:C	donor_loss	1.0000
22:29790465:TCACC:T	donor_loss	1.0000
22:29790466:CAC:C	donor_loss	1.0000
22:29790467:A:AC	donor_gain	1.0000
22:29790467:AC:A	donor_gain	1.0000
22:29790468:C:CC	donor_gain	1.0000
22:29790468:C:G	donor_loss	1.0000
22:29790468:CC:C	donor_gain	1.0000
22:29790544:TCGGG:T	acceptor_gain	1.0000
22:29790545:CGGG:C	acceptor_gain	1.0000
22:29790545:CGGGC:C	acceptor_gain	1.0000
22:29790546:GGG:G	acceptor_gain	1.0000
22:29790546:GGGC:G	acceptor_loss	1.0000
22:29790547:GG:G	acceptor_gain	1.0000
22:29790548:GCTG:G	acceptor_loss	1.0000
22:29790549:C:CC	acceptor_gain	1.0000
22:29790549:CT:C	acceptor_loss	1.0000
22:29790550:T:C	acceptor_loss	1.0000
22:29790551:G:C	acceptor_gain	1.0000
22:29790551:G:GC	acceptor_gain	1.0000
22:29792443:T:TA	donor_gain	1.0000
22:29792542:G:C	acceptor_gain	1.0000
22:29792542:G:GC	acceptor_gain	1.0000
22:29793354:CCTCA:C	donor_loss	1.0000
22:29793355:CTCA:C	donor_loss	1.0000
22:29793356:TCA:T	donor_loss	1.0000
22:29793358:A:AC	donor_gain	1.0000
22:29793358:AC:A	donor_loss	1.0000
22:29793359:C:CC	donor_gain	1.0000

AlphaMissense

5025 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:29789040:C:A	K749N	0.999
22:29789040:C:G	K749N	0.999
22:29789042:T:C	K749E	0.998
22:29790513:T:A	R686S	0.998
22:29790513:T:G	R686S	0.998
22:29790514:C:G	R686T	0.998
22:29825113:G:T	R129S	0.997
22:29825630:A:G	W78R	0.997
22:29825630:A:T	W78R	0.997
22:29790535:A:T	V679D	0.996
22:29790537:A:C	F678L	0.996
22:29790537:A:T	F678L	0.996
22:29790539:A:G	F678L	0.996
22:29789041:T:G	K749T	0.995
22:29789058:T:A	R743S	0.995
22:29789058:T:G	R743S	0.995
22:29790514:C:A	R686I	0.995
22:29816034:A:G	L194P	0.995
22:29822385:A:G	L164P	0.995
22:29825112:C:G	R129P	0.995
22:29825115:A:G	L128P	0.995
22:29789044:C:G	R748P	0.994
22:29789107:C:G	R727P	0.994
22:29789108:G:T	R727S	0.994
22:29802094:A:G	C490R	0.994
22:29802104:G:C	F486L	0.994
22:29802104:G:T	F486L	0.994
22:29802106:A:G	F486L	0.994
22:29802129:A:G	L478P	0.994
22:29825631:G:C	F77L	0.994

dbSNP variants (sampled 300 via entrez): RS1000048199 (22:29800075 T>A), RS1000100839 (22:29820723 T>C,G), RS1000125615 (22:29819392 C>G), RS1000135172 (22:29798481 G>A,T), RS1000196544 (22:29824050 G>A), RS1000220210 (22:29822887 T>C), RS1000225985 (22:29823630 G>A,T), RS1000252244 (22:29829085 A>C), RS1000262746 (22:29817912 T>C), RS1000278670 (22:29816276 G>A,C,T), RS1000283717 (22:29788167 A>G), RS1000484341 (22:29835428 T>C), RS1000484451 (22:29798174 G>A), RS1000633853 (22:29803096 A>T), RS1000698129 (22:29817627 G>A)

Disease associations

OMIM: gene MIM:614216 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002336_2	Telomere length	9.000000e-06
GCST003974_1	Tonsillectomy	1.000000e-09
GCST004001_6	Bipolar disorder or attention deficit hyperactivity disorder	6.000000e-07
GCST004131_67	Inflammatory bowel disease	4.000000e-08
GCST004132_86	Crohn’s disease	8.000000e-07
GCST004628_126	Immature fraction of reticulocytes	2.000000e-18
GCST007516_33	Type 2 diabetes (adjusted for BMI)	4.000000e-14
GCST007518_34	Type 2 diabetes (adjusted for BMI)	1.000000e-12
GCST008568_3	IgA levels	3.000000e-10
GCST009379_303	Type 2 diabetes	1.000000e-12
GCST010002_80	Refractive error	2.000000e-09
GCST010083_238	Hemoglobin levels	8.000000e-09
GCST90002391_176	Mean corpuscular hemoglobin concentration	8.000000e-11
GCST90016667_8	Spleen volume	2.000000e-08

EFO canonical traits (4, from GWAS)

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 (VIP=true, CPIC=false)

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	affects cotreatment, increases methylation, decreases methylation, increases expression	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	affects binding, increases reaction	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 abundance, increases expression	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)

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