ASCC1

Summary

ASCC1 (activating signal cointegrator 1 complex subunit 1, HGNC:24268) is a protein-coding gene on chromosome 10q22.1, encoding Activating signal cointegrator 1 complex subunit 1 (Q8N9N2). Plays a role in DNA damage repair as component of the ASCC complex.

This gene encodes a subunit of the activating signal cointegrator 1 (ASC-1) complex. The ASC-1 complex is a transcriptional coactivator that plays an important role in gene transactivation by multiple transcription factors including activating protein 1 (AP-1), nuclear factor kappa-B (NF-kB) and serum response factor (SRF). The encoded protein contains an N-terminal KH-type RNA-binding motif which is required for AP-1 transactivation by the ASC-1 complex. Mutations in this gene are associated with Barrett esophagus and esophageal adenocarcinoma. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 51008 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinal muscular atrophy with congenital bone fractures 2 (Definitive, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 253 total — 22 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 30
• MANE Select transcript: NM_001198800

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24268
Approved symbol	ASCC1
Name	activating signal cointegrator 1 complex subunit 1
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CGI-18, ASC1p50, Em:AC022392.3, p50
Ensembl gene	ENSG00000138303
Ensembl biotype	protein_coding
OMIM	614215
Entrez	51008

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 25 protein_coding, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000317126, ENST00000317168, ENST00000342444, ENST00000394915, ENST00000461369, ENST00000486689, ENST00000492502, ENST00000524829, ENST00000525286, ENST00000526751, ENST00000526801, ENST00000527593, ENST00000530394, ENST00000530461, ENST00000531048, ENST00000532011, ENST00000533958, ENST00000534259, ENST00000671788, ENST00000672121, ENST00000672774, ENST00000672809, ENST00000672940, ENST00000672957, ENST00000673599, ENST00000902260, ENST00000902261, ENST00000902262, ENST00000902263, ENST00000902264, ENST00000911756, ENST00000957304, ENST00000957305

RefSeq mRNA: 31 — MANE Select: NM_001198800 NM_001198798, NM_001198799, NM_001198800, NM_001369085, NM_001369086, NM_001369087, NM_001369088, NM_001369089, NM_001369090, NM_001369091, NM_001369092, NM_001369093, NM_001369094, NM_001369095, NM_001369096, NM_001369097, NM_001369098, NM_001369099, NM_001369100, NM_001369101, NM_001369102, NM_001369103, NM_001369104, NM_001369105, NM_001369106, NM_001369107, NM_001369108, NM_001369109, NM_001369110, NM_001369111, NM_001369112

CCDS: CCDS31219, CCDS55713, CCDS91259, CCDS91260

Canonical transcript exons

ENST00000672957 — 10 exons

Exon	Start	End
ENSE00000933761	72161538	72161674
ENSE00000933762	72152869	72152988
ENSE00000933763	72133057	72133181
ENSE00001520000	72096032	72097450
ENSE00002187702	72216207	72216276
ENSE00003531520	72210732	72210831
ENSE00003784141	72128082	72128167
ENSE00003784688	72196811	72196989
ENSE00003785997	72203427	72203524
ENSE00003889921	72213187	72213331

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 93.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.0395 / max 221.5980, expressed in 1809 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109986	13.4454	1790
109984	4.8552	1546
109985	2.1650	1290
109983	0.3633	216
109987	0.1125	34
109988	0.0981	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	93.68	gold quality
ventricular zone	UBERON:0003053	93.50	gold quality
sperm	CL:0000019	93.33	gold quality
male germ cell	CL:0000015	92.37	gold quality
corpus callosum	UBERON:0002336	92.33	gold quality
cortical plate	UBERON:0005343	92.19	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.73	gold quality
adrenal tissue	UBERON:0018303	91.54	gold quality
islet of Langerhans	UBERON:0000006	91.41	gold quality
spinal cord	UBERON:0002240	91.26	gold quality
right adrenal gland	UBERON:0001233	91.22	gold quality
right adrenal gland cortex	UBERON:0035827	91.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.99	gold quality
ganglionic eminence	UBERON:0004023	90.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.42	gold quality
left adrenal gland cortex	UBERON:0035825	90.32	gold quality
adrenal gland	UBERON:0002369	90.16	gold quality
left adrenal gland	UBERON:0001234	90.14	gold quality
body of pancreas	UBERON:0001150	90.07	gold quality
adrenal cortex	UBERON:0001235	90.00	gold quality
descending thoracic aorta	UBERON:0002345	89.99	gold quality
heart left ventricle	UBERON:0002084	89.97	gold quality
pancreas	UBERON:0001264	89.95	gold quality
muscle of leg	UBERON:0001383	89.92	gold quality
cardiac ventricle	UBERON:0002082	89.80	gold quality
gastrocnemius	UBERON:0001388	89.75	gold quality
right atrium auricular region	UBERON:0006631	89.51	gold quality
heart	UBERON:0000948	89.35	gold quality
popliteal artery	UBERON:0002250	89.34	gold quality
tibial artery	UBERON:0007610	89.33	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	19.86
E-ANND-3	yes	5.34
E-CURD-112	no	2.98

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 12)

• Gastrin activates paracrine networks leading to induction of PAI-2 via MAZ and ASC-1. (PMID:19074642)
• Three major genes, MSR1, ASCC1, and CTHRC1 were associated with Barrett esophagus/esophageal adenocarcinoma (PMID:21791690)
• ASCC1 inhibits NF-kappaB activation and a truncated and inactive variant of ASCC1 is associated with a more severe disease, which could have clinical value for assessing the progression and prognosis of Rheumatoid Arthritis. (PMID:26503956)
• Our patient was also found to have a homozygous frameshift variant (c.157dupG, p.Glu53Glyfs*19) in ASCC1 , thereby representing the second known case. This confirms ASCC1 involvement in a severe neuromuscular disease lying within the spinal muscular atrophy or primary muscle disease spectra (PMID:28218388)
• ASCC1 knockout through a CRISPR/Cas9 approach results in alkylation damage sensitivity in a manner epistatic with ASCC3. (PMID:29997253)
• this work expands the ASCC1 mutation spectrum, sheds light on the muscle histology of the disorder and emphasises the physiological importance of the ASC-1 complex in fetal muscle and bone development. (PMID:30327447)
• A new case of SMABF2 diagnosed in stillbirth expands the prenatal presentation and mutational spectrum of ASCC1. (PMID:31880396)
• Association between non-Caucasian-specific ASCC1 gene polymorphism and osteoporosis and obesity in Korean postmenopausal women. (PMID:32653958)
• Biallelic ASCC1 variants including a novel intronic variant result in expanded phenotypic spectrum of spinal muscular atrophy with congenital bone fractures 2 (SMABF2). (PMID:33931933)
• Inherited Defects of the ASC-1 Complex in Congenital Neuromuscular Diseases. (PMID:34204919)
• Congenital myopathy as a new phenotype caused by two undescribed variants in ASCC1 gene. (PMID:35838082)
• ASCC1 structures and bioinformatics reveal a novel helix-clasp-helix RNA-binding motif linked to a two-histidine phosphodiesterase. (PMID:38750793)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ascc1	ENSDARG00000077760
mus_musculus	Ascc1	ENSMUSG00000044475
rattus_norvegicus	Ascc1	ENSRNOG00000056647
drosophila_melanogaster	CG12129	FBGN0033475
caenorhabditis_elegans		WBGENE00016019

Protein

Protein identifiers

Activating signal cointegrator 1 complex subunit 1 — Q8N9N2 (reviewed: Q8N9N2)

Alternative names: ASC-1 complex subunit p50, Trip4 complex subunit p50

All UniProt accessions (18): Q8N9N2, A0A5F9ZGP6, A0A5F9ZH79, A0A5F9ZHP1, A0A5F9ZI10, A0A5F9ZI37, A0A5K1VW55, E9PJM2, E9PKM6, E9PL92, E9PM82, E9PQ44, E9PQZ6, E9PR40, H0YCB3, H0YE76, H0YE79, H0YER2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in DNA damage repair as component of the ASCC complex. Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation. In cells responding to gastrin-activated paracrine signals, it is involved in the induction of SERPINB2 expression by gastrin. May also play a role in the development of neuromuscular junction.

Subunit / interactions. Identified in the ASCC complex that contains ASCC1, ASCC2 and ASCC3. Interacts directly with ASCC3. The ASCC complex interacts with ALKBH3. Part of the ASC-1 complex, that contains TRIP4, ASCC1, ASCC2 and ASCC3. Interacts with CSRP1. Interacts with ZCCHC4.

Subcellular location. Nucleus. Nucleus speckle.

Tissue specificity. Ubiquitous.

Disease relevance. Barrett esophagus (BE) [MIM:614266] A condition characterized by a metaplastic change in which normal esophageal squamous epithelium is replaced by a columnar and intestinal-type epithelium. Patients with Barrett esophagus have an increased risk of esophageal adenocarcinoma. The main cause of Barrett esophagus is gastroesophageal reflux. The retrograde movement of acid and bile salts from the stomach into the esophagus causes prolonged injury to the esophageal epithelium and induces chronic esophagitis, which in turn is believed to trigger the pathologic changes. The gene represented in this entry may be involved in disease pathogenesis. Spinal muscular atrophy with congenital bone fractures 2 (SMABF2) [MIM:616867] An autosomal recessive neuromuscular disorder characterized by prenatal-onset spinal muscular atrophy, multiple congenital contractures consistent with arthrogryposis multiplex congenita, respiratory distress, and congenital bone fractures. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N9N2-1	1	yes
Q8N9N2-2	2

RefSeq proteins (31): NP_001185727, NP_001185728, NP_001185729, NP_001356014, NP_001356015, NP_001356016, NP_001356017, NP_001356018, NP_001356019, NP_001356020, NP_001356021, NP_001356022, NP_001356023, NP_001356024, NP_001356025, NP_001356026, NP_001356027, NP_001356028, NP_001356029, NP_001356030, NP_001356031, NP_001356032, NP_001356033, NP_001356034, NP_001356035, NP_001356036, NP_001356037, NP_001356038, NP_001356039, NP_001356040, NP_001356041 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004088	KH_dom_type_1	Domain
IPR009097	Cyclic_Pdiesterase	Homologous_superfamily
IPR009210	ASCC1	Family
IPR019510	AKAP7-like_phosphoesterase	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR047538	KH-I_ASCC1	Domain

Pfam: PF00013, PF10469

UniProt features (10 total): sequence conflict 3, splice variant 2, sequence variant 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8TLY	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N9N2-F1	65.70	0.17

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-112126	ALKBH3 mediated reversal of alkylation damage
R-HSA-73894	DNA Repair
R-HSA-73942	DNA Damage Reversal
R-HSA-73943	Reversal of alkylation damage by DNA dioxygenases

MSigDB gene sets: 242 (showing top): WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, GOBP_DNA_DAMAGE_RESPONSE, MODULE_284, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GCM_NF2, REACTOME_DNA_REPAIR, MEDINA_SMARCA4_TARGETS, TGTYNNNNNRGCARM_UNKNOWN, GOBP_DNA_REPLICATION, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_BODY, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_RIBONUCLEOPROTEIN_GRANULE, GOCC_DNA_REPAIR_COMPLEX, MARSON_BOUND_BY_FOXP3_UNSTIMULATED

GO Biological Process (5): DNA replication (GO:0006260), DNA alkylation repair (GO:0006307), regulation of DNA-templated transcription (GO:0006355), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (3): RNA binding (GO:0003723), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), nuclear speck (GO:0016607), DNA repair complex (GO:1990391)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Reversal of alkylation damage by DNA dioxygenases	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
binding	2
DNA biosynthetic process	1
DNA repair	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
DNA damage response	1
cellular response to stress	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
protein-containing complex	1
nuclear ribonucleoprotein granule	1
catalytic complex	1

Protein interactions and networks

STRING

1335 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASCC1	ASCC2	Q9H1I8	988
ASCC1	ASCC3	Q8N3C0	973
ASCC1	TRIP4	Q15650	897
ASCC1	ZNF598	Q86UK7	547
ASCC1	ZNF862	O60290	523
ASCC1	CTHRC1	Q96CG8	479
ASCC1	MRPL45	Q9BRJ2	440
ASCC1	LENG9	Q96B70	417
ASCC1	PRR13	Q9NZ81	408
ASCC1	E5RHQ9	E5RHQ9	404
ASCC1	ALKBH3	Q96Q83	400
ASCC1	ASAP2	O43150	387
ASCC1	MSR1	P21757	376
ASCC1	ANAPC16	Q96DE5	362
ASCC1	ATL3	Q6DD88	361

IntAct

28 interactions, top by confidence:

A	B	Type	Score
ASCC1	ASCC3	psi-mi:“MI:0915”(physical association)	0.720
ASCC2	TRIP4	psi-mi:“MI:0914”(association)	0.640
ASCC1	TRAF2	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	ASCC1	psi-mi:“MI:0915”(physical association)	0.560
ALKBH3	INPPL1	psi-mi:“MI:0914”(association)	0.530
ASCC1	TRIP4	psi-mi:“MI:0914”(association)	0.530
ASCC1	NAA38	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
KSR1		psi-mi:“MI:0914”(association)	0.350
CD74		psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
rep	STXBP3	psi-mi:“MI:0914”(association)	0.350
EIF3B	EIF3CL	psi-mi:“MI:0914”(association)	0.350
EIF4A1	EIF3F	psi-mi:“MI:0914”(association)	0.350
GSPT1	EIF3CL	psi-mi:“MI:0914”(association)	0.350
PSPC1	MCRIP1	psi-mi:“MI:0914”(association)	0.350
RACK1	RPS3A	psi-mi:“MI:0914”(association)	0.350
RPS11	SCAMP1	psi-mi:“MI:0914”(association)	0.350
RPS16	MCRIP1	psi-mi:“MI:0914”(association)	0.350
SRP9	RPS3A	psi-mi:“MI:0914”(association)	0.350
ASCC1	IGLL5	psi-mi:“MI:0914”(association)	0.350
ASCC2	AMY1A	psi-mi:“MI:0914”(association)	0.350
TRIP4	HAL	psi-mi:“MI:0914”(association)	0.350
RPS10	ZNF316	psi-mi:“MI:0914”(association)	0.350

BioGRID (137): UFSP2 (Affinity Capture-Western), ASCC1 (Affinity Capture-Western), ESR1 (Affinity Capture-Western), ASCC1 (Affinity Capture-Western), EP300 (Affinity Capture-Western), NCOA1 (Affinity Capture-Western), ASCC1 (Two-hybrid), ASCC1 (Affinity Capture-MS), IGKC (Affinity Capture-MS), ASCC3 (Affinity Capture-MS), IGHG2 (Affinity Capture-MS), IGHG1 (Affinity Capture-MS), ASCC2 (Affinity Capture-MS), TRIP4 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS)

ESM2 similar proteins: A8MR21, B2RXH8, B7ZW38, F4JGB7, F4K3M6, O60812, O82312, O82387, O82391, P0DMR1, P83946, P93422, P93831, Q0DZT4, Q0WVE8, Q10MI4, Q149N8, Q3ED78, Q5RBK9, Q5VN06, Q66GQ6, Q680I0, Q6K1U0, Q6K1U4, Q6K5I0, Q6NKT5, Q7TP98, Q7X7E9, Q7ZXY4, Q84JE8, Q84UI6, Q8GW46, Q8GYY5, Q8GZ42, Q8L925, Q8N9N2, Q8NCT3, Q8RXT5, Q8S4P4, Q8S4P5

Diamond homologs: A0A096LPI5, A6NIU2, A6NJG6, F2Z398, P0DTE4, P51957, Q09FC8, Q5H9K5, Q5T7P6, Q68CZ1, Q6B4Z3, Q6UX73, Q86U02, Q8IV13, Q8N7M2, Q8N9N2, Q8NDZ0, Q8NEM8, Q8TDM0, Q92918, Q96J02, Q96MD7, Q9BUA6, Q9NXG0, Q8N2A0, Q96M98, Q96T75, Q9UHC9, A7MB40, P78312, Q8CGI1, A2RRD8, A6NHJ4, P0CJ79, P17035, P51522, Q08AN1, Q0VGE8, Q3MIS6, Q5HY98

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	5	50.4×	9e-07
Translation initiation complex formation	7	49.4×	5e-09
Ribosomal scanning and start codon recognition	7	49.4×	5e-09
Formation of the ternary complex, and subsequently, the 43S complex	6	47.9×	8e-08
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	7	30.5×	8e-08
L13a-mediated translational silencing of Ceruloplasmin expression	7	26.2×	2e-07
GTP hydrolysis and joining of the 60S ribosomal subunit	7	26.0×	2e-07
Formation of a pool of free 40S subunits	6	24.9×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
translational initiation	5	57.8×	5e-06
cytoplasmic translation	5	29.9×	4e-05
translation	5	16.6×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	9
Uncertain significance	77
Likely benign	97
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1029240	NM_001198800.3(ASCC1):c.784C>T (p.Gln262Ter)	Pathogenic
1210120	NC_000010.10:g.(?73970434)(73973122_?)del	Pathogenic
1285416	NM_001198800.3(ASCC1):c.714C>A (p.Tyr238Ter)	Pathogenic
1301895	NM_001198800.3(ASCC1):c.349C>T (p.Arg117Ter)	Pathogenic
1435658	NM_001198800.3(ASCC1):c.295C>T (p.Gln99Ter)	Pathogenic
1452041	NM_001198800.3(ASCC1):c.439C>T (p.Gln147Ter)	Pathogenic
1460373	NC_000010.10:g.(?73970470)(73973056_?)del	Pathogenic
2124744	NM_001198800.3(ASCC1):c.958-5426C>G	Pathogenic
2192453	NM_001198800.3(ASCC1):c.812G>A (p.Trp271Ter)	Pathogenic
2423961	NC_000010.10:g.(?73970470)(73970609_?)del	Pathogenic
2500145	NC_000010.11:g.72138925_72163147del	Pathogenic
2506360	NM_001198800.3(ASCC1):c.464_465del (p.Glu155fs)	Pathogenic
3244962	NC_000010.10:g.(?73956549)(73956767_?)del	Pathogenic
3340123	NM_001198800.3(ASCC1):c.79C>T (p.Gln27Ter)	Pathogenic
3658954	NM_001198800.3(ASCC1):c.958-5483_958-5482insAAAAAAAAGGAAAAAAAAACATAGTATCTATTTCGTGGGGTTGTGAGGACGCAATAAGATAATTCCTGGCACATGTGTTTACTTAATAAATGTTGGCTGTTGTCATCTTTATTACTGTTGTTGTCAATACCTACATATTTCTAGTTCACTTTGATCTTTTTTTTGTTTTGTTTTGAGACAGAGCTTTGCCTTGTTGCCCAGGCTGGAGTACAATGAGC	Pathogenic
3764612	NM_001198800.3(ASCC1):c.411del (p.Ala138fs)	Pathogenic
801334	NM_001198800.3(ASCC1):c.382C>T (p.Arg128Ter)	Pathogenic
801335	NM_001198800.3(ASCC1):c.328C>T (p.Arg110Ter)	Pathogenic
801336	NG_031890.1:g.(?60461)(94053_?)del	Pathogenic
801337	NM_001198800.3(ASCC1):c.943C>T (p.Arg315Ter)	Pathogenic
985780	NM_001198800.3(ASCC1):c.251dup (p.Glu85fs)	Pathogenic
985781	NM_001198800.3(ASCC1):c.311-2A>G	Pathogenic
1931274	NM_001198800.3(ASCC1):c.872-1G>C	Likely pathogenic
2635586	NM_001198800.3(ASCC1):c.649del (p.Pro216_Leu217insTer)	Likely pathogenic
3062021	NM_001198800.3(ASCC1):c.213-8T>G	Likely pathogenic
3244963	NC_000010.10:g.(?73892899)(73901366_?)del	Likely pathogenic
3377184	NM_001198800.3(ASCC1):c.626+2T>A	Likely pathogenic
3377590	NM_001198800.3(ASCC1):c.380_381del (p.Phe127fs)	Likely pathogenic
3381061	NM_001198800.3(ASCC1):c.766C>T (p.Arg256Ter)	Likely pathogenic
3911328	NM_001198800.3(ASCC1):c.604C>T (p.Gln202Ter)	Likely pathogenic

SpliceAI

2629 predictions. Top by Δscore:

Variant	Effect	Δscore
10:72097446:AACAA:A	acceptor_gain	1.0000
10:72097448:CAA:C	acceptor_gain	1.0000
10:72097449:AACT:A	acceptor_loss	1.0000
10:72097450:AC:A	acceptor_loss	1.0000
10:72097451:C:A	acceptor_loss	1.0000
10:72097451:C:CC	acceptor_gain	1.0000
10:72097452:T:G	acceptor_loss	1.0000
10:72128168:C:CC	acceptor_gain	1.0000
10:72133191:T:TC	acceptor_gain	1.0000
10:72152864:TATAC:T	donor_loss	1.0000
10:72152866:TA:T	donor_loss	1.0000
10:72152867:A:AC	donor_loss	1.0000
10:72152868:C:A	donor_loss	1.0000
10:72152987:CA:C	acceptor_gain	1.0000
10:72152989:C:CC	acceptor_gain	1.0000
10:72161532:AC:A	donor_loss	1.0000
10:72161533:CTCA:C	donor_gain	1.0000
10:72161534:TCACT:T	donor_loss	1.0000
10:72161536:A:AC	donor_gain	1.0000
10:72161536:A:T	donor_loss	1.0000
10:72161537:C:A	donor_loss	1.0000
10:72161537:C:CG	donor_gain	1.0000
10:72161537:CTT:C	donor_gain	1.0000
10:72161537:CTTA:C	donor_gain	1.0000
10:72161540:A:AC	donor_gain	1.0000
10:72196805:ACTT:A	donor_loss	1.0000
10:72196806:CTTA:C	donor_loss	1.0000
10:72196808:TA:T	donor_loss	1.0000
10:72196809:A:AC	donor_gain	1.0000
10:72196809:AC:A	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003004 (10:72131514 C>A), RS1000012660 (10:72147775 G>A), RS1000026373 (10:72208478 G>A), RS1000040012 (10:72214339 T>C), RS1000044391 (10:72201669 T>C), RS1000114294 (10:72203161 C>T), RS1000179795 (10:72166231 T>C), RS1000187335 (10:72172742 ATATAT>A), RS1000234969 (10:72128499 G>A), RS1000241904 (10:72188341 A>G), RS1000250535 (10:72206767 T>C), RS1000259905 (10:72104874 C>A), RS1000308486 (10:72212781 G>A), RS1000320846 (10:72121928 C>T), RS1000377351 (10:72172398 G>A,C,T)

Disease associations

OMIM: gene MIM:614215 | disease phenotypes: MIM:616867, MIM:614266, MIM:249900, MIM:617468, MIM:208150, MIM:160150

GenCC curated gene-disease

Disease	Classification	Inheritance
spinal muscular atrophy with congenital bone fractures 2	Definitive	Autosomal recessive

Mondo (6): spinal muscular atrophy with congenital bone fractures 2 (MONDO:0014807), Barrett esophagus (MONDO:0013662), metachromatic leukodystrophy due to saposin B deficiency (MONDO:0009590), arthrogryposis multiplex congenita (MONDO:0015168), fetal akinesia deformation sequence 1 (MONDO:0100101), centronuclear myopathy (MONDO:0018947)

Orphanet (6): Adenocarcinoma of the oesophagus and oesophagogastric junction (Orphanet:99976), Metachromatic leukodystrophy (Orphanet:512), Arthrogryposis multiplex congenita (Orphanet:1037), Fetal akinesia deformation sequence (Orphanet:994), Centronuclear myopathy (Orphanet:595), NON RARE IN EUROPE: Barrett esophagus (Orphanet:1232)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001263	Global developmental delay
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001324	Muscle weakness
HP:0001371	Flexion contracture
HP:0001442	Typified by somatic mosaicism
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001622	Premature birth
HP:0001643	Patent ductus arteriosus
HP:0001655	Patent foramen ovale
HP:0002015	Dysphagia
HP:0002020	Gastroesophageal reflux
HP:0002089	Pulmonary hypoplasia
HP:0002536	Abnormal cortical gyration
HP:0002643	Neonatal respiratory distress
HP:0002804	Arthrogryposis multiplex congenita
HP:0002878	Respiratory failure
HP:0003202	Skeletal muscle atrophy
HP:0003447	Axonal loss
HP:0003477	Peripheral axonal neuropathy
HP:0003557	Increased variability in muscle fiber diameter
HP:0003577	Congenital onset
HP:0004791	Esophageal ulceration
HP:0005855	Multiple prenatal fractures
HP:0006829	Severe muscular hypotonia
HP:0007269	Spinal muscular atrophy
HP:0011459	Esophageal carcinoma
HP:0100580	Barrett esophagus

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006369_9	Body mass index	1.000000e-06
GCST009391_1998	Metabolite levels	8.000000e-06
GCST010063_1	Physiological traits	9.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0010542	ureidopropionic acid measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001471	Barrett Esophagus	C04.834.154; C06.405.117.102
C562609	Metachromatic Leukodystrophy due to Saposin B Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
fenofibric acid	affects binding, increases expression	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
(+)-JQ1 compound	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Ivermectin	decreases expression	1
Testosterone	decreases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	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_D9XW	Ubigene HeLa ASCC1 KO	Cancer cell line	Female
CVCL_SD57	HAP1 ASCC1 (-) 1	Cancer cell line	Male
CVCL_XL57	HAP1 ASCC1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00352261	PHASE4	COMPLETED	An Open Label pH Comparison of Esomeprazole and Lansoprazole in Barrett’s Esophagus Patients
NCT00526786	PHASE4	TERMINATED	Study of CryoSpray Ablation of Low Grade or High Grade Dysplasia Within Barrett’s Esophagus
NCT00628784	PHASE4	UNKNOWN	Endoesophageal Cryotherapy For Ablating Barrett’s Esophagus and Early Stage Esophageal Cancer
NCT00637559	PHASE4	COMPLETED	Barrett’s Esophagus - 315 - 3 Way Cross-Over
NCT00637988	PHASE4	COMPLETED	Barrett’s Esophagus - 315 - 3 Way Cross Over
NCT00754468	PHASE4	COMPLETED	Study of CryoSpray Ablation(TM)to Determine Treatment Effect, Depth of Injury, and Side Effects in the Esophagus.
NCT00872755	PHASE4	COMPLETED	Nissen and Gastroplasty in Gastroesophageal Reflux Disease (GERD)
NCT01030263	PHASE4	TERMINATED	A Trial Comparing Yield of Confocal Endomicroscopy Guided Biopsies
NCT01093755	PHASE4	COMPLETED	Does Intensive Acid Suppression Reduce Esophageal Inflammation and Recurrent Barrett’s Esophagus Following Ablation?
NCT01733147	PHASE4	COMPLETED	Modulation of Esophageal Inflammation in Barrett’s Esophagus by Omega-3 Fatty Acids
NCT02004782	PHASE4	WITHDRAWN	Barretts oEsophageal Resection With Steroid Therapy Trial
NCT00487695	PHASE3	COMPLETED	Confocal Endomicroscopy for Barrett’s Esophagus
NCT01209013	PHASE3	WITHDRAWN	Safety of Photodynamic Therapy (PDT) in the Ablation of High-grade Dysplasia (HGD) in Barrett’s Esophagus (BE)
NCT01566474	PHASE3	COMPLETED	Melatonin Associated to Acid Inhibition for Chemoprevention in Barret Esophagus: a Pilot Study
NCT00217087	PHASE2	COMPLETED	Endoscopic Therapy of Early Cancer in Barretts Esophagus
NCT00220103	PHASE2	COMPLETED	Pre-operative Epirubicin, Cisplatin, and Capecitabine in Patients With Newly Diagnosed Localised Oesophageal Adenocarcinoma
NCT00411151	PHASE2	COMPLETED	Efficacy and Safety of Sunitinib in Metastatic Gastric Cancer
NCT00474903	PHASE2	COMPLETED	Esomeprazole Magnesium With or Without Aspirin in Preventing Esophageal Cancer in Patients With Barrett Esophagus
NCT01097304	PHASE2	COMPLETED	Ursodiol in Treating Patients With Barrett Esophagus and Low-Grade Dysplasia
NCT01298999	PHASE2	COMPLETED	Trial of a Gastrin Receptor Antagonist in Barrett’s Esophagus
NCT01360541	PHASE2	COMPLETED	Radiofrequency Ablation for Barrett Oesophagus With Low Grade Dysplasia
NCT01447927	PHASE2	COMPLETED	Metformin Hydrochloride in Preventing Esophageal Cancer in Patients With Barrett Esophagus
NCT02018367	PHASE2	UNKNOWN	Accuracy, Yield and Clinical Impact of a Low-Cost HRME in the Early Diagnosis of Esophageal Adenocarcinoma
NCT02162758	PHASE2	TERMINATED	Effect of Dexlansoprazole 60 mg QD and 60 mg BID on Recurrence of Intestinal Metaplasia in Subjects Who Have Achieved Complete Eradication of Barrett’s Esophagus With Radiofrequency Ablation
NCT02521285	PHASE2	ACTIVE_NOT_RECRUITING	Aspirin in Preventing Disease Recurrence in Patients With Barrett Esophagus After Successful Elimination by Radiofrequency Ablation
NCT02597712	PHASE2	COMPLETED	YF476 in Barrett’s Esophagus
NCT03877601	PHASE2	UNKNOWN	Detection of Early Esophageal Cancer by NIR-FME.
NCT04939051	PHASE2	RECRUITING	Obeticholic Acid for Prevention in Barrett’s Esophagus
NCT06732388	PHASE2	NOT_YET_RECRUITING	Itraconazole in Combination With Ablation for the Prevention of Esophageal Cancer in Patients With High-risk Barrett’s Esophagus
NCT07260877	PHASE2	RECRUITING	A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study With an Open-Label Extension Evaluating the Efficacy and Safety of VENT-03 in Adult Participants With Active Cutaneous Lupus Erythematosus With or Without Systemic Lupus Erythematosus
NCT00216788	PHASE1	UNKNOWN	The Effect of Nexium on Transmucosal Esophageal Leak
NCT00233935	PHASE1	COMPLETED	Defined Green Tea Catechin Extract in Preventing Esophageal Cancer in Patients With Barrett’s Esophagus
NCT00573911	PHASE1	COMPLETED	Acid Reflux and Stromal Fibroblasts in Barrett’s Esophagus
NCT01236443	PHASE1	COMPLETED	Study of Photodynamic Therapy (PDT) Using HPPH in Barrett’s Esophagus
NCT01238042	PHASE1	COMPLETED	Study To Determine The Maximum Range of Light Doses At Two HPPH Doses With Acceptable Normal Tissue Toxicity For PDT Treatment Of High Grade Dysplasia,CIS or Early Adenocarcinoma In Barrett’s Esophagus
NCT01391208	PHASE1	COMPLETED	Esophageal Protocol for Detection of Neoplasia in the Digestive Tract
NCT01630798	PHASE1	COMPLETED	A In-Vivo Esophageal Protocol for Detection of Neoplasia in the Digestive Tract
NCT01905202	PHASE1	UNKNOWN	The Safety and Tolerability of Secretrol in Patients With Barrett’s Esophagus
NCT03205501	PHASE1	COMPLETED	Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions
NCT03589443	PHASE1	COMPLETED	Study of Multiplexed Heptapeptides for Detection of Neoplasia in the Esophagus