COL15A1

protein-coding

collagen type XV alpha 1 chain, the group of Collagen proteoglycans|Collagens

Gene summary

This gene encodes the alpha chain of type XV collagen, a member of the FACIT collagen family (fibril-associated collagens with interrupted helices). Type XV collagen has a wide tissue distribution but the strongest expression is localized to basement membrane zones so it may function to adhere basement membranes to underlying connective tissue stroma. The proteolytically produced C-terminal fragment of type XV collagen is restin, a potentially antiangiogenic protein that is closely related to endostatin. Mouse studies have shown that collagen XV deficiency is associated with muscle and microvessel deterioration. [provided by RefSeq, May 2013]

MANE transcript

NM_001855.5

Inheritance

—

ClinVar variants

U:243B:57

Top phenotype

COL15A1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr9:98,943,179-99,070,787

External References & Databases

Ensembl (ENSG00000204291)

Transcript & Mutation Effects

hg38 • Region Span ~127.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COL15A1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 228

COL15A1-related disorderTotal: 45

not providedTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001855.5. 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			2 clinvar	17 clinvar	5 clinvar	24
missense			219 clinvar	18 clinvar	17 clinvar	254
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			20 clinvar			20
Total	0	0	243	35	22	300

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001855.5	RefSeq	NP_001846.3	42	MANE Select
ENST00000375001.8	Ensembl	ENSP00000364140.3	42	MANE Select
ENST00000873219.1	Ensembl	ENSP00000543278.1	42	Standard
ENST00000873219.2	Ensembl	ENSP00000543278.1	42	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
col15a1a	Danio rerio	Structure: primary motor neuron Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

col15a1a

Danio rerio

Structure: primary motor neuron

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein digestion and absorption - Homo sapiens (human)
Assembly of collagen fibrils and other multimeric structures
Collagen chain trimerization
Collagen biosynthesis and modifying enzymes
Collagen formation

Biological Process

angiogenesis
cell adhesion
signal transduction
cell differentiation
extracellular matrix organization

Molecular Function

extracellular matrix structural constituent
extracellular matrix structural constituent conferring tensile strength

Cellular Component

extracellular region
collagen type XV trimer
extracellular space
endoplasmic reticulum lumen
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375001
Coding exons: 42
Length: 127609
Individuals with no LoFs: 125183
Homozygous LoFs: 1
Heterozygous LoFs: 564
Defined: 125748
p: 0.00225

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.120	798	808	0.988	0.0000437	8846
Missense (PolyPhen)		296	311.87	0.94912		3253
Synonymous	-0.898	341	321	1.06	0.0000202	2952
Loss of Function	5.05	27	73.8	0.366	0.00000372	866

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0013	0.0012	notable
Latino/Admixed American	0.0014	0.0014	notable
Ashkenazi Jewish	0.0079	0.0080	notable
East Asian	0.00088	0.00087	rare
Finnish	0.0018	0.0018	notable
European (Non-Finnish)	0.0018	0.0018	notable
South Asian	0.0046	0.0046	notable
Other	0.0028	0.0028	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Structural protein that stabilizes microvessels and muscle cells, both in heart and in skeletal muscle. {ECO:0000269|PubMed:10049780}.;

Intolerance Scores

LoFtool: 0.0931
RVIS EVS: 1.84
RVIS percentile EVS: 97.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0880

Gene Damage Prediction

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