COL27A1

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

Basic information

Region (hg38): 9:114155537-114312511

Links

ENSG00000196739 ∙ NCBI:85301 ∙ OMIM:608461 ∙ HGNC:22986 ∙ Uniprot:Q8IZC6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Steel syndrome (Strong), mode of inheritance: AR
• Steel syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Steel syndrome	AR	Musculoskeletal	Outcomes have been described as better without the use of surgical treatment for hip dislocations	Craniofacial; Musculoskeletal	8423186; 24986830

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL27A1 gene.

• not provided (64 variants)
• Steel syndrome (10 variants)
• Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL27A1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	822	40	863
missense	2	2	321	60	23	408
nonsense	22	4				26
start loss						0
frameshift	44	5				49
inframe indel			3			3
splice donor/acceptor (+/-2bp)	4	51	1	1		57
splice region		1	11	199	3	214
non coding			5	475	48	528
Total	72	62	331	1358	111

Highest pathogenic variant AF is 0.000315

Variants in COL27A1

This is a list of pathogenic ClinVar variants found in the COL27A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-114155954-G-A		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
9-114155957-G-A		Inborn genetic diseases	Uncertain significance (Jan 17, 2023)
9-114155961-G-C			Uncertain significance (Oct 24, 2022)
9-114155962-A-G			Likely benign (Feb 17, 2023)
9-114155965-G-A			Likely benign (Aug 11, 2023)
9-114155968-G-A			Likely benign (Jan 23, 2022)
9-114155970-G-T			Likely benign (Jan 24, 2024)
9-114155971-G-C			Likely benign (Dec 06, 2020)
9-114155974-G-A			Likely benign (Apr 13, 2023)
9-114155974-G-C			Likely benign (Nov 01, 2023)
9-114155977-C-G			Likely benign (Jan 28, 2024)
9-114155986-A-G			Likely benign (Jan 25, 2024)
9-114155989-G-A			Likely benign (Aug 09, 2022)
9-114155992-G-A			Likely benign (Jun 12, 2022)
9-114155992-G-T			Likely benign (Oct 10, 2023)
9-114155995-G-A			Likely benign (Aug 07, 2020)
9-114155997-C-T			Uncertain significance (Aug 26, 2021)
9-114156001-G-A			Likely benign (Dec 21, 2023)
9-114156001-G-C			Likely benign (Jun 10, 2021)
9-114156004-G-A			Likely benign (Jan 28, 2024)
9-114156007-C-G			Likely benign (Jun 20, 2023)
9-114156007-CG-C		Steel syndrome	Pathogenic/Likely pathogenic (Jan 24, 2024)
9-114156010-G-C			Likely benign (Nov 06, 2023)
9-114156010-G-T			Likely benign (Jan 29, 2024)
9-114156013-G-C			Likely pathogenic (Dec 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL27A1	protein_coding	protein_coding	ENST00000356083	61	156952

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.586	0.414	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.629	1060	1.12e+3	0.947	0.0000709	11618
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

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.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization (Consensus)

Intolerance Scores

• loftool: 0.0176
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.34

Haploinsufficiency Scores

• pHI: 0.701
• hipred: N
• hipred_score: 0.417
• ghis: 0.517

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.145

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Col27a1
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; respiratory system phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); limbs/digits/tail phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: col27a1a
• Affected structure: vertebral column
• Phenotype tag: abnormal
• Phenotype quality: curved lateral

Gene ontology

• Biological process: growth plate cartilage chondrocyte development;extracellular matrix organization
• Cellular component: extracellular region;fibrillar collagen trimer;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix
• Molecular function: extracellular matrix structural constituent;extracellular matrix structural constituent conferring tensile strength;metal ion binding