ATXN7L3

protein-coding

ataxin 7 like 3, the group of SAGA complex

Gene summary

Enables transcription coactivator activity. Involved in positive regulation of DNA-templated transcription and regulation of transcription by RNA polymerase II. Located in nucleus. Part of DUBm complex and SAGA complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001382309.1

Inheritance

ClinVar variants

P:1U:38B:4

Top phenotype

complex neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr17:44,191,805-44,200,113

External References & Databases

Ensembl (ENSG00000087152)

Transcript & Mutation Effects

hg38 • Region Span ~8.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

Mendelian neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100500

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATXN7L3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 24

not providedTotal: 11

See casesTotal: 5

Harel-Tora neurodevelopmental syndromeTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001382309.1. 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	2 clinvar	1 clinvar	5
missense		1 clinvar	28 clinvar	1 clinvar		30
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	1	38	3	1	43

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001382309.1	RefSeq	NP_001369238.1	12	MANE Select
ENST00000587097.6	Ensembl	ENSP00000465614.2	12	MANE Select
NM_001382308.1	RefSeq	NP_001369237.1	12	Standard
NM_001382310.1	RefSeq	NP_001369239.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Chromatin modifying enzymes
HATs acetylate histones
Chromatin organization

Biological Process

histone monoubiquitination
histone deubiquitination
positive regulation of transcription, DNA-templated

Molecular Function

transcription coactivator activity
protein binding
zinc ion binding
nuclear receptor transcription coactivator activity

Cellular Component

SAGA complex
nucleus
DUBm complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000454077
Coding exons: 12
Length: 8309
Individuals with no LoFs: 124784
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 124786
p: 0.00000801

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.05	134	220	0.610	0.0000135	2356
Missense (PolyPhen)		9	56.395	0.15959		639
Synonymous	-0.673	93	85.1	1.09	0.00000558	627
Loss of Function	4.37	1	24.2	0.0413	0.00000137	257

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the transcription regulatory histone acetylation (HAT) complex SAGA, a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. Within the SAGA complex, participates in a subcomplex that specifically deubiquitinates both histones H2A and H2B (PubMed:18206972, PubMed:21746879). The SAGA complex is recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation. Within the complex, it is required to recruit USP22 and ENY2 into the SAGA complex (PubMed:18206972). Regulates H2B monoubiquitination (H2Bub1) levels. Affects subcellular distribution of ENY2, USP22 and ATXN7L3B (PubMed:27601583). {ECO:0000255|HAMAP-Rule:MF_03047, ECO:0000269|PubMed:18206972, ECO:0000269|PubMed:21746879, ECO:0000269|PubMed:27601583}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.134
RVIS EVS: -0.63
RVIS percentile EVS: 17.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.832

Gene Damage Prediction

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