COL27A1

protein-coding

collagen type XXVII alpha 1 chain, the group of MicroRNA protein coding host genes|Collagens

Gene summary

This gene encodes a member of the fibrillar collagen family, and plays a role during the calcification of cartilage and the transition of cartilage to bone. The encoded protein product is a preproprotein. It includes an N-terminal signal peptide, which is followed by an N-terminal propetide, mature peptide and a C-terminal propeptide. The N-terminal propeptide contains thrombospondin N-terminal-like and laminin G-like domains. The mature peptide is a major triple-helical region. The C-terminal propeptide, also known as COLFI domain, plays crucial roles in tissue growth and repair. Mutations in this gene cause Steel syndrome. Alternatively spliced transcript variants have been found, but the full-length nature of some variants has not been determined. [provided by RefSeq, Sep 2014]

MANE transcript

NM_032888.4

Inheritance

ClinVar variants

P:164U:548B:1024

Top phenotype

Steel syndrome

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr9:114,155,537-114,312,511

External References & Databases

Ensembl (ENSG00000196739)

Transcript & Mutation Effects

hg38 • Region Span ~157.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Steel syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014061

Submitter: Orphanet

Steel syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014061

Submitter: G2P

Steel syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014061

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Steel syndromeAR

Manifestation: Craniofacial; Musculoskeletal

Intervention: Musculoskeletal

Rationale: Outcomes have been described as better without the use of surgical treatment for hip dislocations

Refs: 8423186; 24986830

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COL27A1 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 2142

Inborn genetic diseasesTotal: 342

not specifiedTotal: 168

Steel syndromeTotal: 66

COL27A1-related disorderTotal: 39

COL27A1-related disordersTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032888.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	12 clinvar	892 clinvar	17 clinvar	922
missense	2 clinvar	4 clinvar	517 clinvar	103 clinvar	12 clinvar	638
nonsense	23 clinvar	10 clinvar				33
start loss						0
frameshift	44 clinvar	15 clinvar	1 clinvar			60
splice donor/acceptor (+/-2bp)	9 clinvar	56 clinvar	18 clinvar			83
Total	78	86	548	995	29	1736

Highest pathogenic variant AF is 0.000057618603

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032888.4	RefSeq	NP_116277.2	61	MANE Select
ENST00000356083.8	Ensembl	ENSP00000348385.3	61	MANE Select
ENST00000451716.5	Ensembl	ENSP00000391328.1	8	Standard
ENST00000494090.6	Ensembl	ENSP00000432928.1	14	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
col27a1a	Danio rerio	Structure: vertebral column Quality: curved lateral abnormal

Gene / Model

Organism

Observed Phenotype

col27a1a

Danio rerio

Structure: vertebral column

Quality: curved lateral

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein digestion and absorption - Homo sapiens (human)
Collagen chain trimerization
Collagen biosynthesis and modifying enzymes
Collagen formation
Extracellular matrix organization

Biological Process

growth plate cartilage chondrocyte development
extracellular matrix organization

Molecular Function

extracellular matrix structural constituent
extracellular matrix structural constituent conferring tensile strength
metal ion binding

Cellular Component

extracellular region
fibrillar collagen trimer
extracellular space
endoplasmic reticulum lumen
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356083
Coding exons: 61
Length: 156952
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125748
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.629	1060	1.12e+3	0.947	0.0000709	11618
Missense (PolyPhen)		67	95.849	0.69902		966
Synonymous	-1.11	482	452	1.07	0.0000301	4090
Loss of Function	7.51	24	108	0.222	0.00000540	1246

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role during the calcification of cartilage and the transition of cartilage to bone. {ECO:0000269|PubMed:17693149}.;
Disease: DISEASE: Steel syndrome (STLS) [MIM:615155]: A syndrome characterized by dislocated hips and radial heads, fusion of carpal bones, short stature, scoliosis, and cervical spine anomalies. Facial features include prominent forehead, long oval- shaped face, hypertelorism and broad nasal bridge. {ECO:0000269|PubMed:24986830}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.0176
RVIS EVS: 0.17
RVIS percentile EVS: 65.34

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.145

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High