ASXL1

Chr 20AD

ASXL transcriptional regulator 1

Also known as: BOPS, MDS

NCBI Gene: 171023 ENSG00000171456 UniProt: Q8IXJ9 OMIM: 612990

The protein functions as a chromatin-binding Polycomb group member that disrupts chromatin to enhance transcription of certain genes while repressing others, and acts as a ligand-dependent co-activator for retinoic acid receptor. Mutations cause Bohring-Opitz syndrome and myelodysplastic syndrome through an autosomal dominant inheritance pattern. The pathogenic mechanism involves disrupted chromatin regulation affecting gene transcription patterns.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

LOFmechanismADLOEUF 0.792 OMIM phenotypes

Clinical Summary— ASXL1

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Gene-Disease Validity (ClinGen)

Bohring-Opitz syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 128 VUS of 200 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

0.79LOEUF

pLI 0.000

Z-score 2.77

OE 0.59 (0.44–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint

0.64Z-score

OE missense 0.94 (0.88–0.99)

791 obs / 842.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.59 (0.44–0.79)

0≤0.351.4

Missense OE0.94 (0.88–0.99)

0≤0.61.4

Synonymous OE1.03

0≤1.21.6

LoF obs/exp: 31 / 52.7Missense obs/exp: 791 / 842.9Syn Z: -0.42

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveASXL1-related Bohring-Opitz syndromeLOFAD

0.5575th %ile

GOF

0.4382th %ile

LOF

0.51top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF1 literature citation

GOF1 literature citation

Literature Evidence

GOFAdditional sex combs-like 1 (ASXL1) is frequently mutated in a variety of myeloid malignancies, resulting in expression of a C-terminal-truncated ASXL1 protein that confers gain of function on the ASXL1-BAP1 deubiquitinase (DUB) complex.PMID:34186160

LOFDe novo nonsense mutations in ASXL1 cause Bohring-Opitz syndromePMID:21706002

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS128

Likely Benign70

Pathogenic

128

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	1	0	2
Likely Pathogenic	0	0	0	0	0
VUS	0	128	0	0	128
Likely Benign	0	8	2	60	70
Benign	0	0	0	0	0
Total	1	136	3	60	200

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ASXL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Myeloproliferative Neoplasms

Registry of Patients With MPNs in Taiwan

ACTIVE NOT RECRUITING

NCT03618485Chang Gung Memorial HospitalStarted 2017-04-01

Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING

NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21

NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies

Bone Marrow Failure DisordersVEXAS SyndromeHemoglobinurea, Paroxysmal

Molecular and Clinical Analysis of Bone Marrow Failure: A Secondary Research Study

ENROLLING BY INVITATION

NCT07102849National Heart, Lung, and Blood Institute (NHLBI)Started 2025-09-09

Giant Cell ArteritisTemporal ArteritisClonal Hematopoiesis of Indeterminate Potential

Clonal Hematopoiesis in Giant Cell Arteritis

NOT YET RECRUITING

NCT06244069ASST Fatebenefratelli SaccoStarted 2024-03

Temporal arterial biopsyWhole exome sequencingSingle cell transcriptomics

AMLMDS

Molecular Genetics Guide the Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation

RECRUITING

NCT06972641Phase PHASE2, PHASE3Ruijin HospitalStarted 2025-06-10

DecitabineSorafenib (BAY-43-9006)，giritinibAvastinib

Myeloproliferative Neoplasm

Impact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC)

RECRUITING

NCT06022328University Hospital, BordeauxStarted 2023-12-15

Assessment of the epigenetic age

Leukemia, Myeloid, AcuteMyeloid DysplasiaOvarian Epithelial Cancer

Genetic Landscape in Women with Metastatic Ovarian Cancer Before and During Treatment with PARP Inhibitors

RECRUITING

NCT06785077Phase NAEuropean Institute of OncologyStarted 2020-10-02

buccal cellsbone marrow cellsperipheral blood cells

Diffuse Large B Cell Lymphoma

Characterization and Clinical Impact of the Gut Microbiota in Lymphoma

RECRUITING

NCT06161896Lars Møller PedersenStarted 2024-05-06