ASCL3

protein-coding

achaete-scute family bHLH transcription factor 3, the group of Basic helix-loop-helix proteins

Gene summary

Basic helix-loop-helix transcription factors, such as ASCL3, are essential for the determination of cell fate and the development and differentiation of numerous tissues (Jonsson et al., 2004 [PubMed 15475265]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_020646.3

Inheritance

—

ClinVar variants

U:34B:1

Top phenotype

Preeclampsia

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr11:8,937,578-8,943,016

External References & Databases

Ensembl (ENSG00000176009)

Transcript & Mutation Effects

hg38 • Region Span ~5.4 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 ASCL3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 34

PreeclampsiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020646.3. 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						0
missense			34 clinvar	1 clinvar		35
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	34	1	0	35

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020646.3	RefSeq	NP_065697.1	1	MANE Select
ENST00000531618.2	Ensembl	ENSP00000435770.1	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity

Cellular Component

RNA polymerase II transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000325884
Coding exons: 1
Length: 5462
Individuals with no LoFs: 125529
Homozygous LoFs: 1
Heterozygous LoFs: 216
Defined: 125746
p: 0.000863

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.122	105	109	0.967	0.00000626	1176
Missense (PolyPhen)		34	36.114	0.94146		381
Synonymous	0.703	37	42.9	0.863	0.00000244	371
Loss of Function	0.585	3	4.31	0.696	2.65e-7	53

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.0026	0.0026	notable
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0010	0.0010	notable
South Asian	0.000033	0.000033	rare
Other	0.00081	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor. Inhibits myogenesis (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0991

Intolerance Scores

LoFtool: 0.336
RVIS EVS: 0.59
RVIS percentile EVS: 82.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.406

Gene Damage Prediction

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