COL22A1

protein-coding

collagen type XXII alpha 1 chain, the group of Collagens

Gene summary

This gene encodes member of the collagen family which is thought to contribute to the stabilization of myotendinous junctions and strengthen skeletal muscle attachments during contractile activity. It belongs to the fibril-associated collagens with interrupted triple helix (FACIT) subset of the collagen superfamily, which associate with collagen fibers through their C-terminal collagenous domains and mediate protein-protein interactions through their N-terminal noncollagenous domains. The encoded protein is deposited in the basement membrane zone of the myotendinous junction which is present only at the tissue junctions of muscles, tendons, the heart, articular cartilage, and skin. A knockdown of the orthologous zebrafish gene induces a muscular dystrophy by disruption of the myotendinous junction. [provided by RefSeq, May 2017]

MANE transcript

NM_152888.3

Inheritance

—

ClinVar variants

U:323B:22

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr8:138,588,235-138,914,041

External References & Databases

Ensembl (ENSG00000169436)

Transcript & Mutation Effects

hg38 • Region Span ~325.8 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 COL22A1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 306

not providedTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152888.3. 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			7 clinvar	4 clinvar	1 clinvar	12
missense			301 clinvar	15 clinvar	2 clinvar	318
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			14 clinvar			14
Total	0	0	323	19	3	345

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152888.3	RefSeq	NP_690848.1	64	MANE Select
ENST00000303045.11	Ensembl	ENSP00000303153.6	64	MANE Select
ENST00000522546.1	Ensembl	ENSP00000428244.1	2	Standard
ENST00000903590.1	Ensembl	ENSP00000573649.1	63	Standard

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

extracellular matrix organization

Molecular Function

extracellular matrix structural constituent

Cellular Component

extracellular region
collagen trimer
extracellular space
endoplasmic reticulum lumen
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000303045
Coding exons: 64
Length: 325772
Individuals with no LoFs: 125511
Homozygous LoFs: 1
Heterozygous LoFs: 236
Defined: 125748
p: 0.000943

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.367	996	964	1.03	0.0000593	10061
Missense (PolyPhen)		63	59.301	1.0624		616
Synonymous	-1.08	389	363	1.07	0.0000232	3492
Loss of Function	2.23	83	108	0.768	0.00000586	1245

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0016	0.0016	notable
Latino/Admixed American	0.0010	0.00098	notable
Ashkenazi Jewish	0.00080	0.00079	rare
East Asian	0.0014	0.0014	notable
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00071	0.00069	rare
South Asian	0.0018	0.0018	notable
Other	0.00066	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a cell adhesion ligand for skin epithelial cells and fibroblasts.;

Intolerance Scores

LoFtool: 0.0681
RVIS EVS: 0.16
RVIS percentile EVS: 64.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0576

Gene Damage Prediction

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