ASCL5

Summary

ASCL5 (achaete-scute family bHLH transcription factor 5, HGNC:33169) is a protein-coding gene on chromosome 1q32.1, encoding Achaete-scute homolog 5 (Q7RTU5). Transcription factor.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. Predicted to be part of RNA polymerase II transcription regulator complex.

Source: NCBI Gene 647219 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 2 total — 1 likely-pathogenic
• MANE Select transcript: NM_001270601

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33169
Approved symbol	ASCL5
Name	achaete-scute family bHLH transcription factor 5
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	bHLHa47, ASH-5, AmeloD
Ensembl gene	ENSG00000232237
Ensembl biotype	protein_coding
OMIM	620809
Entrez	647219

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000449188

RefSeq mRNA: 1 — MANE Select: NM_001270601 NM_001270601

CCDS: CCDS59202

Canonical transcript exons

ENST00000449188 — 2 exons

Exon	Start	End
ENSE00001662950	201127084	201127184
ENSE00001698446	201113943	201115877

Expression profiles

Bgee: expression breadth broad, 90 present calls, max score 61.40.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0334 / max 9.6912, expressed in 10 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16604	0.0334	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	61.40	gold quality
prefrontal cortex	UBERON:0000451	56.82	gold quality
nucleus accumbens	UBERON:0001882	54.15	gold quality
pancreas	UBERON:0001264	53.53	gold quality
gastrocnemius	UBERON:0001388	52.42	gold quality
hypothalamus	UBERON:0001898	52.12	gold quality
muscle of leg	UBERON:0001383	51.65	gold quality
frontal cortex	UBERON:0001870	51.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	51.57	gold quality
neocortex	UBERON:0001950	50.82	gold quality
anterior cingulate cortex	UBERON:0009835	50.43	gold quality
right frontal lobe	UBERON:0002810	49.99	gold quality
stromal cell of endometrium	CL:0002255	49.85	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	49.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	49.08	silver quality
ganglionic eminence	UBERON:0004023	48.83	silver quality
cerebral cortex	UBERON:0000956	48.75	gold quality
amygdala	UBERON:0001876	48.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	48.17	silver quality
Brodmann (1909) area 46	UBERON:0006483	47.87	gold quality
forebrain	UBERON:0001890	47.36	gold quality
ventricular zone	UBERON:0003053	47.00	gold quality
right coronary artery	UBERON:0001625	46.94	gold quality
middle temporal gyrus	UBERON:0002771	46.49	gold quality
brain	UBERON:0000955	46.32	gold quality
bone marrow cell	CL:0002092	46.31	gold quality
buccal mucosa cell	CL:0002336	45.81	gold quality
left ovary	UBERON:0002119	45.71	gold quality
skeletal muscle tissue	UBERON:0001134	45.69	silver quality
Ammon’s horn	UBERON:0001954	45.47	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting ASCL5, 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-765	99.84	68.24	2442
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-15A-3P	97.47	65.08	527
HSA-MIR-4529-5P	96.74	65.77	569
HSA-MIR-151A-5P	95.79	68.73	162
HSA-MIR-151B	95.79	68.73	162
HSA-MIR-4749-5P	92.16	62.26	179
HSA-MIR-6767-5P	90.00	62.41	97
HSA-MIR-6089	89.72	61.35	324

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ascl5	ENSMUSG00000097918
rattus_norvegicus	Ascl5	ENSRNOG00000033391
drosophila_melanogaster	ac	FBGN0000022
drosophila_melanogaster	ase	FBGN0000137
drosophila_melanogaster	l(1)sc	FBGN0002561
drosophila_melanogaster	sc	FBGN0004170
caenorhabditis_elegans		WBGENE00001958

Paralogs (4): ASCL1 (ENSG00000139352), ASCL3 (ENSG00000176009), ASCL2 (ENSG00000183734), ASCL4 (ENSG00000187855)

Protein

Protein identifiers

Achaete-scute homolog 5 — Q7RTU5 (reviewed: Q7RTU5)

Alternative names: Class A basic helix-loop-helix protein 47

All UniProt accessions (1): M0R2M9

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor. Probably binds E-box motifs 5’-CANNTG-3’ in complex with transcription factor TCF3/E12. Negatively modulates transcription of target genes such as CDH1/E-cadherin, perhaps by recruiting the PRC2 repressive complex to regulatory elements. Regulates ameloblast development and tooth germ growth, perhaps acting by positively modulating migration of inner enamel epithelium (IEE) cells. Plays a role in enamel formation.

Subunit / interactions. Interacts with transcription factor TCF3/E12.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_001257530* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR050283	E-box_TF_Regulators	Family

Pfam: PF00010

UniProt features (5 total): region of interest 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTU5-F1	64.17	0.19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOMF_DNA_BINDING_TRANSCRIPTION_REPRESSOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ID1_TARGET_GENES, GOCC_NUCLEAR_PROTEIN_CONTAINING_COMPLEX, CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_UP, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_RNA_BIOSYNTHETIC_PROCESS

GO Biological Process (7): regulation of transcription by RNA polymerase II (GO:0006357), animal organ development (GO:0048513), epithelium development (GO:0060429), negative regulation of transcription by RNA polymerase II (GO:0000122), ameloblast differentiation (GO:0036305), positive regulation of transcription by RNA polymerase II (GO:0045944), amelogenesis (GO:0097186)

GO Molecular Function (8): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), protein dimerization activity (GO:0046983), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor binding (GO:0140297)

GO Cellular Component (4): chromatin (GO:0000785), RNA polymerase II transcription regulator complex (GO:0090575), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
transcription by RNA polymerase II	3
regulation of transcription by RNA polymerase II	3
DNA-binding transcription factor activity, RNA polymerase II-specific	2
regulation of DNA-templated transcription	1
anatomical structure development	1
tissue development	1
negative regulation of DNA-templated transcription	1
columnar/cuboidal epithelial cell differentiation	1
positive regulation of DNA-templated transcription	1
odontogenesis of dentin-containing tooth	1
anatomical structure formation involved in morphogenesis	1
transcription cis-regulatory region binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1
protein binding	1
cis-regulatory region sequence-specific DNA binding	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription factor binding	1
chromosome	1
cellular anatomical structure	1
transcription regulator complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASCL5	ACSL5	Q9ULC5	541
ASCL5	BHLHE23	Q8NDY6	540
ASCL5	BHLHA9	Q7RTU4	532
ASCL5	TMEM170B	Q5T4T1	483
ASCL5	TCF24	Q7RTU0	389
ASCL5	H1-0	P07305	371
ASCL5	ZNF316	A6NFI3	370
ASCL5	MFSD6L	Q8IWD5	323
ASCL5	C2orf69	Q8N8R5	316
ASCL5	TCF23	Q7RTU1	312
ASCL5	H2AL3	A0A3B3IU63	311
ASCL5	FTCDNL1	E5RQL4	311
ASCL5	GPR25	O00155	297
ASCL5	TYW5	A2RUC4	296
ASCL5	ZNF141	Q15928	293

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ASCL5	H1-5	psi-mi:“MI:0915”(physical association)	0.400
ASCL5	H1-2	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2R8Y2Y2, A0A494C0N9, A0A494C0Y3, A0JNN8, A6NF83, A6NHQ4, A6QPM6, A8E4L3, A8MTW9, B2KGE5, C9JVW0, I3L1E1, O43541, O75474, O75638, P0C7X2, P70339, P89439, Q02080, Q05215, Q12950, Q3SYB3, Q5T230, Q5VV16, Q6NZ36, Q6NZY7, Q6P1X6, Q6VB84, Q6VUC0, Q6VUP9, Q6ZSJ8, Q7RTU5, Q7TNS8, Q80WY3, Q86SI9, Q86UU5, Q8K025

Diamond homologs: A8E5T6, M0QWB7, O35437, O35885, O43680, O60682, O73615, O73823, O88940, O93507, O96004, O96642, P09774, P09775, P10083, P10084, P10627, P13903, P17542, P19359, P19360, P22091, P24899, P26687, P27792, P34555, P46581, P48985, P50553, P57100, P57101, P57102, P59101, P61295, P61296, P79782, P97831, P97832, Q02067, Q02575

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3358881	NM_001270601.2(ASCL5):c.274G>A (p.Glu92Lys)	Likely pathogenic

SpliceAI

228 predictions. Top by Δscore:

Variant	Effect	Δscore
1:201114636:T:TA	donor_gain	0.9400
1:201114816:TCCGG:T	donor_gain	0.9200
1:201114817:CCGGC:C	donor_gain	0.9200
1:201114579:T:TA	donor_gain	0.9100
1:201114641:CAG:C	donor_gain	0.9100
1:201114692:C:CA	donor_gain	0.9000
1:201114650:T:TA	donor_gain	0.8900
1:201114958:G:C	donor_gain	0.8500
1:201114643:G:C	donor_gain	0.8300
1:201114973:A:AC	donor_gain	0.8100
1:201114974:C:CC	donor_gain	0.8100
1:201114523:TC:T	donor_gain	0.8000
1:201114580:C:A	donor_gain	0.7700
1:201114721:T:TA	donor_gain	0.7500
1:201114975:T:C	donor_gain	0.7400
1:201114382:CGCCT:C	acceptor_loss	0.7200
1:201114383:GCCTG:G	acceptor_loss	0.7200
1:201114385:C:A	acceptor_loss	0.7200
1:201114386:T:A	acceptor_loss	0.7200
1:201114570:C:A	donor_gain	0.7100
1:201114563:CCCG:C	donor_gain	0.7000
1:201114553:G:A	donor_gain	0.6900
1:201114589:G:C	donor_gain	0.6900
1:201114765:T:TA	donor_gain	0.6900
1:201114642:A:C	donor_gain	0.6800
1:201114675:AACAG:A	donor_gain	0.6800
1:201114775:C:CA	donor_gain	0.6800
1:201114521:CT:C	donor_gain	0.6700
1:201114522:TT:T	donor_gain	0.6700
1:201114970:G:C	donor_gain	0.6600

AlphaMissense

1296 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000229543 (1:201122892 C>A), RS1000417627 (1:201117487 C>T), RS1000533832 (1:201117234 G>A), RS1000560651 (1:201121600 C>A), RS1000747570 (1:201115661 A>G), RS1000904375 (1:201126605 C>A,T), RS1000952953 (1:201115432 C>T), RS1000990149 (1:201121437 T>C), RS1001379310 (1:201126283 G>T), RS1001523714 (1:201126920 G>A), RS1001556792 (1:201122266 C>T), RS1001621940 (1:201120981 G>A), RS1001650170 (1:201122046 C>T), RS1001777462 (1:201122625 G>A,T), RS1002153985 (1:201116181 T>TA)

Disease associations

OMIM: gene MIM:620809 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005389_1	Tooth agenesis	2.000000e-16

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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