COL27A1

Chr 9AR

collagen type XXVII alpha 1 chain

Also known as: STLS

NCBI Gene: 85301ENSG00000196739UniProt: Q8IZC6OMIM: 608461

The protein is a fibrillar collagen that functions during cartilage calcification and the transition of cartilage to bone. Autosomal recessive mutations cause Steel syndrome, a skeletal dysplasia characterized by bone and cartilage abnormalities. The pathogenic mechanism involves disruption of normal bone and cartilage development due to defective collagen function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.311 OMIM phenotype
Clinical Summary— COL27A1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.59) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 226 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.586
Z-score 7.51
OE 0.22 (0.16–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.63Z-score
OE missense 0.95 (0.90–1.00)
1060 obs / 1119.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.16–0.31)
0≤0.351.4
Missense OE0.95 (0.90–1.00)
0≤0.61.4
Synonymous OE1.07
0≤1.21.6
LoF obs/exp: 24 / 108.3Missense obs/exp: 1060 / 1119.2Syn Z: -1.11

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic17
VUS226
Likely Benign199
Benign2
Conflicting2
12
Pathogenic
17
Likely Pathogenic
226
VUS
199
Likely Benign
2
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
3
0
12
Likely Pathogenic
12
2
3
0
17
VUS
0
223
2
1
226
Likely Benign
0
3
141
55
199
Benign
0
0
1
1
2
Conflicting
—2
Total2122815057458

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

View in ClinVar →

Protein Context — Lollipop Plot

COL27A1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Mutations in COL1A1 and COL27A1 Associated with a Pectus Excavatum Phenotype in 2 Siblings with Osteogenesis Imperfecta.
Cruz-Centeno N et al.·Am J Case Rep
2022Case report
First reported case of Steel syndrome in the European population: A novel homozygous mutation in COL27A1 and review of the literature.
Evie Kritioti et al.·Eur J Med Genet
2020Review
Functional biology of the Steel syndrome founder allele and evidence for clan genomics derivation of COL27A1 pathogenic alleles worldwide.
Gonzaga-Jauregui C et al.·Eur J Hum Genet
2020Case report
Bioinformatics Analysis and Experimental Verification Identify Downregulation of COL27A1 in Poor Segmental Congenital Scoliosis.
Hu Z et al.·Comput Math Methods Med
2022
Three new patients with Steel syndrome and a Puerto Rican specific COL27A1 mutation.
Amlie-Wolf L et al.·Am J Med Genet A
2020Case report
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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