ATXN7L3B

Summary

ATXN7L3B (ataxin 7 like 3B, HGNC:37931) is a protein-coding gene on chromosome 12q21.1, encoding Ataxin-7-like protein 3B (Q96GX2). By binding to ENY2, interferes with the nuclear functions of the deubiquitinase (DUB) module of the SAGA complex which consists of ENY2, ATXN7, ATXN7L3 and the histone deubiquitinating component USP22.

Involved in regulation of gene expression. Located in cytoplasm.

Source: NCBI Gene 552889 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 21 total — 3 pathogenic
• MANE Select transcript: NM_001136262

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37931
Approved symbol	ATXN7L3B
Name	ataxin 7 like 3B
Location	12q21.1
Locus type	gene with protein product
Status	Approved
Aliases	lnc-SCA7
Ensembl gene	ENSG00000253719
Ensembl biotype	protein_coding
OMIM	615579
Entrez	552889

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000519948

RefSeq mRNA: 1 — MANE Select: NM_001136262 NM_001136262

CCDS: CCDS53815

Canonical transcript exons

ENST00000519948 — 1 exons

Exon	Start	End
ENSE00002122485	74537835	74545430

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.1964 / max 465.2137, expressed in 1819 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126887	43.2595	1819
126889	1.2388	434
126888	0.8658	416
126891	0.5946	342
126890	0.2377	77

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
postcentral gyrus	UBERON:0002581	98.30	gold quality
parietal lobe	UBERON:0001872	98.15	gold quality
pylorus	UBERON:0001166	97.79	gold quality
paraflocculus	UBERON:0005351	97.66	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.61	gold quality
pons	UBERON:0000988	97.47	gold quality
superior frontal gyrus	UBERON:0002661	97.47	gold quality
frontal pole	UBERON:0002795	97.47	gold quality
endometrium epithelium	UBERON:0004811	97.46	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.46	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.37	gold quality
superior vestibular nucleus	UBERON:0007227	97.33	gold quality
entorhinal cortex	UBERON:0002728	97.26	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.25	gold quality
middle temporal gyrus	UBERON:0002771	97.14	gold quality
cardia of stomach	UBERON:0001162	97.05	gold quality
inferior olivary complex	UBERON:0002127	96.97	gold quality
medulla oblongata	UBERON:0001896	96.88	gold quality
lateral globus pallidus	UBERON:0002476	96.82	gold quality
type B pancreatic cell	CL:0000169	96.80	gold quality
orbitofrontal cortex	UBERON:0004167	96.78	gold quality
substantia nigra pars compacta	UBERON:0001965	96.72	gold quality
ventral tegmental area	UBERON:0002691	96.70	gold quality
CA1 field of hippocampus	UBERON:0003881	96.66	gold quality
globus pallidus	UBERON:0001875	96.51	gold quality
medial globus pallidus	UBERON:0002477	96.46	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.42	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.39	gold quality
renal medulla	UBERON:0000362	96.29	gold quality
nasal cavity epithelium	UBERON:0005384	96.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

133 targeting ATXN7L3B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-5582-3P	99.86	72.48	4221

Literature-anchored findings (GeneRIF, showing 5)

• This family’s complex phenotype is associated with a new chromosomal deletion, which suggests potential roles for the two genes, KCNC2 and ATXN7L3B, in human neurological disease. (PMID:23475819)
• Study reports that ATXN7L3B interacts with ENY2 but not other SAGA components. Even though ATXN7L3B localizes in the cytoplasm, ATXN7L3B overexpression increases H2Bub1 levels, while overexpression of ATXN7L3 decreases H2Bub1 levels. (PMID:27601583)
• Potential regulatory SNPs in the ATXN7L3B and KRT15 genes are associated with gender-specific colorectal cancer risk. (PMID:31797724)
• Distinct effects on mRNA export factor GANP underlie neurological disease phenotypes and alter gene expression depending on intron content. (PMID:32202298)
• ATXN7L3B promotes hepatocellular carcinoma stemness and is downregulated by metformin. (PMID:34375763)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Atxn7l3b	ENSMUSG00000074748
rattus_norvegicus	Atxn7l3b	ENSRNOG00000083408
drosophila_melanogaster	Sgf11	FBGN0036804

Paralogs (4): ATXN7L3 (ENSG00000087152), ATXN7L1 (ENSG00000146776), ATXN7L2 (ENSG00000162650), ATXN7 (ENSG00000163635)

Protein

Protein identifiers

Ataxin-7-like protein 3B — Q96GX2 (reviewed: Q96GX2)

All UniProt accessions (1): Q96GX2

UniProt curated annotations — full annotation on UniProt →

Function. By binding to ENY2, interferes with the nuclear functions of the deubiquitinase (DUB) module of the SAGA complex which consists of ENY2, ATXN7, ATXN7L3 and the histone deubiquitinating component USP22. Affects USP22 DUB activity toward histones indirectly by changing the subcellular distribution of ENY2 and altering ENY2 availability for ATXN7L3 interaction. Regulates H2B monoubiquitination (H2Bub1) levels through cytoplasmic sequestration of ENY2 resulting in loss of nuclear ENY2-ATXN7L3 association which destabilizes ATXN7L3. Affects protein expression levels of ENY2 and ATXN7L3.

Subunit / interactions. Interacts strongly with ENY2. Interacts weakly with USP22.

Subcellular location. Cytoplasm.

Disease relevance. A chromosomal aberration involving ATXN7L3B has been found in a mother and her two children with varying degrees of neurodevelopmental delay and cerebellar ataxia. One child also exhibits episodes of unresponsiveness suggestive of absence seizures and facial dysmorphism. Deletion at 12q21.1 deletes the entire single exon of ATXN7L3B.

Miscellaneous. Encoded by an expressed retrotransposed copy of the ATXN7L3 locus that emerged prior to the speciation event separating primates and rodents.

Similarity. Belongs to the SGF11 family.

RefSeq proteins (1): NP_001129734* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR042933	ATXN7L3B	Family

UniProt features (3 total): chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GX2-F1	67.96	0.28

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 92

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 134 (showing top): RODWELL_AGING_KIDNEY_NO_BLOOD_DN, MARTINEZ_RB1_TARGETS_UP, chr12q21, MARTINEZ_RB1_AND_TP53_TARGETS_UP, EPPERT_LSC_R, TOOKER_GEMCITABINE_RESISTANCE_UP, KAMMINGA_SENESCENCE, CAMP_UP.V1_UP, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_UP, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_IFNAR_KO_UP, CBX7_TARGET_GENES, F10_TARGET_GENES, FOXJ2_TARGET_GENES, GSE10240_CTRL_VS_IL22_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_UP, TERF1_TARGET_GENES

GO Biological Process (1): regulation of gene expression (GO:0010468)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gene expression	1
regulation of macromolecule biosynthetic process	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATXN7L3B	ATXN7	O15265	655
ATXN7L3B	ENY2	Q9NPA8	642
ATXN7L3B	CIMAP1C	Q8IXM7	578
ATXN7L3B	CGGBP1	Q9UFW8	490
ATXN7L3B	URB1	O60287	473
ATXN7L3B	BICD2	Q8TD16	420
ATXN7L3B	KCNC2	Q96PR1	418
ATXN7L3B	CLN8	Q9UBY8	414
ATXN7L3B	THAP12	O43422	412
ATXN7L3B	OLA1	Q9NTK5	411
ATXN7L3B	TCERG1	O14776	410
ATXN7L3B	TSPYL4	Q9UJ04	404
ATXN7L3B	ATXN7L2	Q5T6C5	398
ATXN7L3B	ATXN7L1	Q9ULK2	390
ATXN7L3B	RAPGEF1	Q13905	387

IntAct

7 interactions, top by confidence:

A	B	Type	Score
LRRK2		psi-mi:“MI:0914”(association)	0.350
USP22	CNOT1	psi-mi:“MI:0914”(association)	0.350
ENY2	EIF3CL	psi-mi:“MI:0914”(association)	0.350
LARP7	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
ZC3H11A	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (23): ATXN7L3B (Affinity Capture-MS), ATXN7L3B (Affinity Capture-MS), ATXN7L3B (Affinity Capture-MS), ATXN7L3B (Affinity Capture-MS), ATXN7L3B (Affinity Capture-RNA), ENY2 (Affinity Capture-MS), USP22 (Affinity Capture-MS), TAF6L (Affinity Capture-MS), TAF10 (Affinity Capture-MS), TADA3 (Affinity Capture-MS), ENY2 (Affinity Capture-Western), USP22 (Affinity Capture-Western), ATXN7L3B (Affinity Capture-Western), ATXN7L3B (Affinity Capture-Western), ATXN7L3B (Reconstituted Complex)

ESM2 similar proteins: A4J2H0, A7IFY5, A7Y3E0, A8W7N6, A9IW23, B1ILB1, B1NWF3, O10337, O28329, O29734, O29982, O30602, O64254, O86223, P02881, P09134, P0CW38, P0DKT6, P0DM50, P0DQP6, P11389, P12195, P20031, P20413, P22920, P37102, P39431, P39495, P80268, P81342, P81496, P83687, P83722, P84990, P85924, P86599, P86906, Q05275, Q06GJ8, Q12FC6

Diamond homologs: A1L209, A2AWT3, A5DZI5, A7TSM3, B0W8L4, B1PM81, B3M881, B3NHQ1, B4GZZ4, B4IFU5, B4J1U4, B4J1U5, B4KY72, B4LDA6, B4MVH6, B4N4E1, B4PJ01, B4QPV0, Q14CW9, Q17CJ5, Q2LYX9, Q3UD01, Q5FC18, Q751G1, Q7PXG4, Q94BV2, Q96GX2, Q9VVR6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1180525	GRCh37/hg19 12q14.3-21.1(chr12:65251705-75263379)x1	Pathogenic
147046	GRCh38/hg38 12q15-21.2(chr12:69769737-76964217)x1	Pathogenic
4075888	GRCh37/hg19 12q21.1-21.31(chr12:74893196-80534739)x1	Pathogenic

SpliceAI

222 predictions. Top by Δscore:

Variant	Effect	Δscore
12:74538468:GGA:G	donor_gain	0.9800
12:74538469:GAG:G	donor_gain	0.9800
12:74538476:C:G	donor_gain	0.9800
12:74538471:G:GG	donor_gain	0.9700
12:74542899:T:TA	acceptor_gain	0.9600
12:74538316:A:T	donor_gain	0.9500
12:74538417:A:T	donor_gain	0.9500
12:74538421:TCTGA:T	donor_gain	0.9400
12:74538476:C:CG	donor_gain	0.9400
12:74538066:GCC:G	donor_gain	0.9200
12:74538466:GAGGA:G	donor_gain	0.9200
12:74538069:G:GG	donor_gain	0.9100
12:74538315:G:GT	donor_gain	0.9100
12:74538469:GA:G	donor_gain	0.9100
12:74538475:GC:G	donor_gain	0.8900
12:74538403:G:GG	donor_gain	0.8600
12:74538402:A:AG	donor_gain	0.8500
12:74538305:G:GT	donor_gain	0.8000
12:74538065:TGCC:T	donor_gain	0.7800
12:74538066:GCCG:G	donor_gain	0.7800
12:74538274:T:TA	donor_gain	0.7800
12:74538275:A:AA	donor_gain	0.7800
12:74538395:G:GT	donor_gain	0.7700
12:74538425:A:T	donor_gain	0.7700
12:74538436:GACAA:G	donor_gain	0.7700
12:74538218:G:GC	acceptor_gain	0.7600
12:74538468:G:GT	donor_gain	0.7400
12:74538674:G:GT	donor_gain	0.7400
12:74538900:TGC:T	donor_gain	0.7400
12:74538065:TGCCG:T	donor_loss	0.7300

AlphaMissense

629 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:74538206:G:A	G32R	0.995
12:74538206:G:C	G32R	0.995
12:74538228:G:C	R39P	0.995
12:74538186:T:C	L25P	0.994
12:74538207:G:A	G32E	0.994
12:74538165:C:A	A18D	0.993
12:74538238:G:C	K42N	0.993
12:74538238:G:T	K42N	0.993
12:74538212:T:C	C34R	0.992
12:74538214:C:G	C34W	0.991
12:74538200:T:C	C30R	0.990
12:74538213:G:A	C34Y	0.987
12:74538230:G:C	A40P	0.987
12:74538234:T:A	V41D	0.987
12:74538204:T:C	L31S	0.985
12:74538224:C:G	H38D	0.985
12:74538236:A:G	K42E	0.985
12:74538207:G:T	G32V	0.982
12:74538243:G:T	G44V	0.982
12:74538164:G:C	A18P	0.980
12:74538194:G:C	D28H	0.980
12:74538202:T:G	C30W	0.980
12:74538210:T:C	F33S	0.980
12:74538216:T:C	F35S	0.980
12:74538197:T:C	S29P	0.978
12:74538186:T:A	L25Q	0.977
12:74538237:A:T	K42M	0.976
12:74538222:T:A	V37E	0.974
12:74538174:T:G	I21S	0.973
12:74538186:T:G	L25R	0.971

dbSNP variants (sampled 300 via entrez): RS1000852905 (12:74542527 A>G), RS1000971439 (12:74537396 A>G), RS1001318867 (12:74537112 G>A), RS1001431151 (12:74537131 A>T), RS1001545410 (12:74536809 A>T), RS1001761351 (12:74541128 G>C), RS1001855998 (12:74541282 G>T), RS1002715420 (12:74545529 T>G), RS1002860957 (12:74540014 A>G), RS1003690729 (12:74540870 A>C,G), RS1003712804 (12:74543978 C>A,T), RS1003775965 (12:74538492 A>T), RS1003870802 (12:74538663 A>C,G), RS1004667042 (12:74543246 A>G), RS1004753111 (12:74542959 A>G)

Disease associations

OMIM: gene MIM:615579 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005588_4	Idiopathic dilated cardiomyopathy	2.000000e-06
GCST011743_52	HDL cholesterol levels in HIV infection	4.000000e-06
GCST011768_17	Schizophrenia	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium	increases abundance, increases expression, decreases expression	2
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
resorcinol	increases expression	1
tamibarotene	affects expression	1
monomethylarsonous acid	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
torcetrapib	increases expression	1
ICG 001	decreases expression	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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