ACVRL1

Chr 12

activin A receptor like type 1

Also known as: ACVRLK1, ALK-1, ALK1, HHT, HHT2, ORW2, SKR3, TSR-I

NCBI Gene: 94ENSG00000139567UniProt: P37023

This gene encodes a type I cell-surface receptor for the TGF-beta superfamily of ligands. It shares with other type I receptors a high degree of similarity in serine-threonine kinase subdomains, a glycine- and serine-rich region (called the GS domain) preceding the kinase domain, and a short C-terminal tail. The encoded protein, sometimes termed ALK1, shares similar domain structures with other closely related ALK or activin receptor-like kinase proteins that form a subfamily of receptor serine/threonine kinases. Mutations in this gene are associated with hemorrhagic telangiectasia type 2, also known as Rendu-Osler-Weber syndrome 2. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtTelangiectasia, hereditary hemorrhagic, 2

Clinical highlights

Gene-disease validity (ClinGen)
telangiectasia, hereditary hemorrhagic, type 2 · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
4
Active trials
82
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.69
LOEUF
LOF*
Mechanism· G2P
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GeneReview available — ACVRL1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.69LOEUF
pLI 0.001
Z-score 2.66
OE 0.40 (0.24–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
2.45Z-score
OE missense 0.61 (0.54–0.69)
190 obs / 311.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.40 (0.24–0.69)
0≤0.351.4
Missense OE?0.61 (0.54–0.69)
0≤0.61.4
Synonymous OE?1.05
0≤1.21.6
LoF obs/exp: 9 / 22.7Missense obs/exp: 190 / 311.5Syn Z: -0.45

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ACVRL1 · protein map & ClinVar variants

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

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