ASCC3

protein-coding

activating signal cointegrator 1 complex subunit 3, the group of RNA helicases|DNA helicases|Activating signal cointegrator 1 complex

Gene summary

This gene encodes a protein that belongs to a family of helicases that are involved in the ATP-dependent unwinding of nucleic acid duplexes. The encoded protein is the largest subunit of the activating signal cointegrator 1 complex that is involved in DNA repair and resistance to alkylation damage. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

Previous symbols:

HELIC1

MANE transcript

NM_006828.4

Inheritance

ClinVar variants

P:19U:314B:61

Top phenotype

Intellectual developmental disorder, autosomal recessive 81

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr6:100,508,194-100,881,372

External References & Databases

Ensembl (ENSG00000112249)

Transcript & Mutation Effects

hg38 • Region Span ~373.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, autosomal recessive 81STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0958204

Submitter: PanelApp Australia

intellectual disabilityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

intellectual developmental disorder, autosomal recessive 81LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0958204

Submitter: G2P

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal recessive 81AR

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 21937992; 35047834

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ASCC3 variants in ClinVar

9 Conditions Cataloged

Inborn genetic diseasesTotal: 236

not providedTotal: 103

not specifiedTotal: 40

Intellectual developmental disorder, autosomal recessive 81Total: 20

ASCC3-related conditionTotal: 11

Congenital myopathyTotal: 2

ASCC3-related disorderTotal: 2

See casesTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006828.4. 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			2 clinvar	43 clinvar	3 clinvar	48
missense	5 clinvar	2 clinvar	286 clinvar	12 clinvar	3 clinvar	308
nonsense	1 clinvar	4 clinvar	6 clinvar			11
start loss						0
frameshift	2 clinvar	2 clinvar	7 clinvar			11
splice donor/acceptor (+/-2bp)		3 clinvar	13 clinvar			16
Total	8	11	314	55	6	394

Highest pathogenic variant AF is 0.00003595432

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006828.4	RefSeq	NP_006819.2	41	MANE Select
ENST00000369162.7	Ensembl	ENSP00000358159.2	41	MANE Select
NM_001284271.2	RefSeq	NP_001271200.1	12	Standard
NM_022091.5	RefSeq	NP_071374.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mesodermal Commitment Pathway
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
cell population proliferation
DNA duplex unwinding

Molecular Function

RNA binding
protein binding
ATP binding
ATP-dependent helicase activity
ATP-dependent 3'-5' DNA helicase activity

Cellular Component

nucleus
nucleoplasm
cytosol
membrane
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369162
Coding exons: 41
Length: 373179
Individuals with no LoFs: 125464
Homozygous LoFs: 0
Heterozygous LoFs: 284
Defined: 125748
p: 0.00113

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.23	938	1.15e+3	0.815	0.0000587	14534
Missense (PolyPhen)		268	433.44	0.61831		5255
Synonymous	-0.371	402	393	1.02	0.0000192	4154
Loss of Function	5.58	55	121	0.453	0.00000739	1391

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0038	0.0038	notable
Latino/Admixed American	0.00075	0.00075	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0014	0.0014	notable
Finnish	0.0027	0.0027	notable
European (Non-Finnish)	0.00084	0.00081	rare
South Asian	0.00043	0.00042	rare
Other	0.0011	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: 3'-5' DNA helicase involved in repair of alkylated DNA. Promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3, enabling ALKBH3 to process alkylated N3- methylcytosine (3mC) within double-stranded regions (PubMed:22055184). Part of the ASC-1 complex that enhances NF- kappa-B, SRF and AP1 transactivation (PubMed:12077347). {ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:22055184}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.780
RVIS EVS: 0.13
RVIS percentile EVS: 63.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.968

Gene Damage Prediction

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