ASCL3

Summary

ASCL3 (achaete-scute family bHLH transcription factor 3, HGNC:740) is a protein-coding gene on chromosome 11p15.4, encoding Achaete-scute homolog 3 (Q9NQ33). Transcriptional repressor.

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]).

Source: NCBI Gene 56676 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_020646

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:740
Approved symbol	ASCL3
Name	achaete-scute family bHLH transcription factor 3
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	bHLHa42, HASH3, Sgn1
Ensembl gene	ENSG00000176009
Ensembl biotype	protein_coding
OMIM	609154
Entrez	56676

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000531618

RefSeq mRNA: 1 — MANE Select: NM_020646 NM_020646

CCDS: CCDS7795

Canonical transcript exons

ENST00000531618 — 2 exons

Exon	Start	End
ENSE00002200903	8937578	8938173
ENSE00003934416	8942986	8943016

Expression profiles

Bgee: expression breadth broad, 51 present calls, max score 76.33.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	76.33	gold quality
hair follicle	UBERON:0002073	72.99	gold quality
minor salivary gland	UBERON:0001830	70.77	gold quality
saliva-secreting gland	UBERON:0001044	69.76	gold quality
mouth mucosa	UBERON:0003729	67.11	gold quality
bone marrow cell	CL:0002092	65.83	gold quality
parotid gland	UBERON:0001831	63.60	gold quality
mucosa of paranasal sinus	UBERON:0005030	58.52	gold quality
nasal cavity mucosa	UBERON:0001826	57.61	gold quality
colonic epithelium	UBERON:0000397	57.05	gold quality
decidua	UBERON:0002450	56.55	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
sural nerve	UBERON:0015488	47.88	silver quality
cranial nerve II	UBERON:0000941	47.39	silver quality
periodontal ligament	UBERON:0008266	47.14	gold quality
renal glomerulus	UBERON:0000074	46.86	gold quality
metanephric glomerulus	UBERON:0004736	46.77	gold quality
nephron tubule	UBERON:0001231	46.71	gold quality
tonsil	UBERON:0002372	46.37	gold quality
bone marrow	UBERON:0002371	46.01	gold quality
nasal cavity epithelium	UBERON:0005384	45.90	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
palpebral conjunctiva	UBERON:0001812	44.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
gingiva	UBERON:0001828	43.36	gold quality
renal medulla	UBERON:0000362	42.66	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
medulla oblongata	UBERON:0001896	42.39	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	12.12
E-ANND-3	no	1.63

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CD74
ERVW-4

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ascl1a	ENSDARG00000038386
mus_musculus	Ascl3	ENSMUSG00000035951
rattus_norvegicus	Tmem9b	ENSRNOG00000013591
drosophila_melanogaster	ac	FBGN0000022
drosophila_melanogaster	ase	FBGN0000137

Paralogs (4): ASCL1 (ENSG00000139352), ASCL2 (ENSG00000183734), ASCL4 (ENSG00000187855), ASCL5 (ENSG00000232237)

Protein

Protein identifiers

Achaete-scute homolog 3 — Q9NQ33 (reviewed: Q9NQ33)

Alternative names: Class A basic helix-loop-helix protein 42, bHLH transcriptional regulator Sgn-1

All UniProt accessions (1): Q9NQ33

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor. Inhibits myogenesis. Plays a role in progenitor cells which differentiate into ductal and acinar, but not myoepithelial, cell lineages in the salivary glands. Involved in the functions of the microvillar cells and Bowman’s glands and probably, in a non-cell-autonomous manner, in the development or regeneration of a complete olfactory epithelium (OE).

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed in fetal and adult tissues.

RefSeq proteins (1): NP_065697* (*=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 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQ33-F1	69.74	0.31

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_SALIVARY_GLAND_DEVELOPMENT, GOBP_GROWTH, GOBP_REGENERATION, NFKB_Q6, NFKB_C, GOBP_EXOCRINE_SYSTEM_DEVELOPMENT, OCT1_06, GOBP_TISSUE_REGENERATION, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, IK3_01, OCT1_B, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOBP_HOMEOSTATIC_PROCESS

GO Biological Process (8): tissue homeostasis (GO:0001894), regulation of transcription by RNA polymerase II (GO:0006357), salivary gland development (GO:0007431), positive regulation of transcription by RNA polymerase II (GO:0045944), sensory epithelium regeneration (GO:0070654), negative regulation of transcription by RNA polymerase II (GO:0000122), animal organ development (GO:0048513), epithelium development (GO:0060429)

GO Molecular Function (6): 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), DNA binding (GO:0003677), protein dimerization activity (GO:0046983), protein binding (GO:0005515)

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
transcription by RNA polymerase II	3
regulation of transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
multicellular organismal-level homeostasis	1
anatomical structure homeostasis	1
regulation of DNA-templated transcription	1
exocrine system development	1
gland development	1
positive regulation of DNA-templated transcription	1
epithelium regeneration	1
negative regulation of DNA-templated transcription	1
anatomical structure development	1
tissue development	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 factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
nucleic acid binding	1
protein binding	1
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

464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASCL3	ACSL3	O95573	590
ASCL3	TRPM5	Q9NZQ8	559
ASCL3	MYOD1	P15172	559
ASCL3	CFTR	P13569	538
ASCL3	ACBD6	Q9BR61	510
ASCL3	DRC12	Q494R4	483
ASCL3	FOXI1	Q12951	482
ASCL3	ZNF23	P17027	475
ASCL3	KRT5	P13647	449
ASCL3	GHITM	Q9H3K2	449
ASCL3	SOWAHB	A6NEL2	441
ASCL3	BSCL2	Q96G97	438
ASCL3	CFAP263	Q9H0I3	430
ASCL3	VPS13A	Q96RL7	411
ASCL3	GPAT4	Q86UL3	410

IntAct

20 interactions, top by confidence:

A	B	Type	Score
TCF3	ASCL3	psi-mi:“MI:0915”(physical association)	0.560
TCF4	ASCL3	psi-mi:“MI:0915”(physical association)	0.560
TCF12	ASCL3	psi-mi:“MI:0915”(physical association)	0.560
ASCL3	HEMK1	psi-mi:“MI:0915”(physical association)	0.560
VPS37C	ASCL3	psi-mi:“MI:0915”(physical association)	0.560
ID1	ASCL3	psi-mi:“MI:0915”(physical association)	0.560
ASCL3	TCF4	psi-mi:“MI:0914”(association)	0.350
ASCL3	TCF3	psi-mi:“MI:0915”(physical association)	0.000
ASCL3	TCF4	psi-mi:“MI:0915”(physical association)	0.000
ASCL3	TCF12	psi-mi:“MI:0915”(physical association)	0.000
HEMK1	ASCL3	psi-mi:“MI:0915”(physical association)	0.000
VPS37C	ASCL3	psi-mi:“MI:0915”(physical association)	0.000
ID1	ASCL3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): ASCL3 (Two-hybrid), ASCL3 (Two-hybrid), ASCL3 (Two-hybrid), ASCL3 (Two-hybrid), ASCL3 (Two-hybrid), TCF4 (Two-hybrid), TCF12 (Affinity Capture-MS), TCF3 (Affinity Capture-MS), TCF4 (Affinity Capture-MS), ID4 (Affinity Capture-MS), C2orf49 (Affinity Capture-MS), ASCL3 (Affinity Capture-MS), ASCL3 (Positive Genetic), ASCL3 (Two-hybrid), ASCL3 (Two-hybrid)

ESM2 similar proteins: A8E5T6, O35437, O43680, O57598, O73615, O93507, O96642, P13349, P13903, P13904, P15375, P16075, P16076, P17667, P19335, P23409, P24699, P24700, P32314, P57101, P57102, P59101, P70661, P79782, P79920, P97831, Q02576, Q10574, Q18277, Q23579, Q32PV5, Q4ZHW1, Q5E9S3, Q62282, Q6GNB7, Q6NYU3, Q6PUV5, Q6SYV5, Q7YS80, Q7ZSX3

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

147 predictions. Top by Δscore:

Variant	Effect	Δscore
11:8937965:C:A	donor_gain	0.7900
11:8938144:G:A	donor_gain	0.7800
11:8937964:T:A	donor_gain	0.7600
11:8937955:A:AC	donor_gain	0.7300
11:8937956:C:CC	donor_gain	0.7300
11:8937960:AATTT:A	donor_gain	0.6900
11:8938007:T:TA	donor_gain	0.6800
11:8938079:G:T	donor_gain	0.6800
11:8937865:ATT:A	donor_gain	0.6700
11:8937867:T:A	donor_gain	0.6600
11:8937902:TCG:T	donor_gain	0.6500
11:8937903:CGC:C	donor_gain	0.6500
11:8937795:C:CA	donor_gain	0.6400
11:8937857:T:A	donor_gain	0.6300
11:8938163:T:TA	donor_gain	0.6200
11:8938077:A:AC	donor_gain	0.5800
11:8937839:CATT:C	donor_gain	0.5700
11:8937931:C:CT	acceptor_gain	0.5400
11:8938057:G:T	donor_gain	0.5400
11:8938055:G:C	donor_gain	0.5300
11:8937932:G:T	acceptor_gain	0.5200
11:8937952:T:C	donor_gain	0.5200
11:8937825:AG:A	donor_gain	0.5100
11:8938008:C:CA	donor_gain	0.5100
11:8937911:C:CC	acceptor_gain	0.5000
11:8938141:G:C	donor_gain	0.4900
11:8937907:CCCT:C	acceptor_gain	0.4800
11:8937908:CCTC:C	acceptor_gain	0.4800
11:8937909:CT:C	acceptor_gain	0.4700
11:8937752:G:C	donor_gain	0.4500

AlphaMissense

1182 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000893749 (11:8942513 A>G), RS1001257752 (11:8940087 C>G), RS1002242743 (11:8937261 G>T), RS1002380408 (11:8943272 A>G), RS1003043222 (11:8938363 C>T), RS1003273134 (11:8938545 G>A), RS1003354285 (11:8944172 C>G), RS1004381739 (11:8943314 T>A,C), RS1004746775 (11:8942039 T>C), RS1004817154 (11:8943491 T>C), RS1005051832 (11:8941404 G>A), RS1005122431 (11:8941688 A>T), RS1005209582 (11:8938809 T>C), RS1005470909 (11:8941192 A>T), RS1005722122 (11:8938612 G>A)

Disease associations

OMIM: gene MIM:609154 | disease phenotypes: MIM:189800

GenCC curated gene-disease

Mondo (1): preeclampsia (MONDO:0005081)

Orphanet (1): Preeclampsia (Orphanet:275555)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005950_10	Body mass index x sex x age interaction (4df test)	6.000000e-11
GCST005951_51	Body mass index	8.000000e-11
GCST005953_4	Body mass index (age <50)	4.000000e-11
GCST010703_171	Brain morphology (MOSTest)	5.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011225	Pre-Eclampsia	C12.050.703.395.249

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Coal	increases abundance, increases expression	1
Methotrexate	decreases expression	1
Smoke	increases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	PHASE4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	PHASE4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	PHASE4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	PHASE4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164	PHASE4	UNKNOWN	162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952	PHASE4	UNKNOWN	co Ihibtory Receptor in Preeclampsia
NCT05514847	PHASE4	ACTIVE_NOT_RECRUITING	Low Dose Aspirin for Preterm Preeclampsia Preventionmg/day Dose in High-risk Patients
NCT05586373	PHASE4	COMPLETED	Ibuprofen vs Dipyrone After C-section in Preeclampsia
NCT06069102	PHASE4	COMPLETED	Optimal Blood Pressure Treatment Thresholds Postpartum
NCT06107335	PHASE4	NOT_YET_RECRUITING	Effect of Albumin Versus Routine Care on Hemodynamic Response and Stability in Patients With Preeclampsia Guided by a Non-invasive Hemodynamic Monitoring System During Cesarean Delivery With Spinal Anesthesia
NCT06281665	PHASE4	RECRUITING	Treatment With Aspirin After Preeclampsia: TAP Trial