ASCC2

protein-coding

activating signal cointegrator 1 complex subunit 2, the group of Activating signal cointegrator 1 complex

Gene summary

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. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_032204.5

Inheritance

—

ClinVar variants

U:116B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr22:29,788,609-29,838,304

External References & Databases

Ensembl (ENSG00000100325)

Transcript & Mutation Effects

hg38 • Region Span ~49.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ASCC2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 111

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032204.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense			112 clinvar	3 clinvar		115
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	116	4	0	120

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 210 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032204.5	RefSeq	NP_115580.2	19	MANE Select
ENST00000307790.8	Ensembl	ENSP00000305502.3	19	MANE Select
NM_001242906.2	RefSeq	NP_001229835.1	18	Standard
NM_001369920.1	RefSeq	NP_001356849.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

DNA Repair
ALKBH3 mediated reversal of alkylation damage
Reversal of alkylation damage by DNA dioxygenases
DNA Damage Reversal

Biological Process

DNA dealkylation involved in DNA repair
regulation of transcription, DNA-templated

Cellular Component

nucleus
nucleoplasm
nuclear speck
activating signal cointegrator 1 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397771
Coding exons: 19
Length: 49675
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125747
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.21	377	449	0.839	0.0000271	4982
Missense (PolyPhen)		73	95.056	0.76796		1006
Synonymous	1.28	167	189	0.881	0.0000130	1433
Loss of Function	4.33	11	40.9	0.269	0.00000197	468

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: 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 (PubMed:29144457). Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation (PubMed:12077347). {ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:29144457}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.652
RVIS EVS: 0.58
RVIS percentile EVS: 82.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.909

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium