COL13A1

protein-coding

collagen type XIII alpha 1 chain, the group of Collagens

Gene summary

This gene encodes the alpha chain of one of the nonfibrillar collagens. The function of this gene product is not known, however, it has been detected at low levels in all connective tissue-producing cells so it may serve a general function in connective tissues. Unlike most of the collagens, which are secreted into the extracellular matrix, collagen XIII contains a transmembrane domain and the protein has been localized to the plasma membrane. The transcripts for this gene undergo complex and extensive splicing involving at least eight exons. Like other collagens, collagen XIII is a trimer; it is not known whether this trimer is composed of one or more than one alpha chain isomer. A number of alternatively spliced transcript variants have been described, but the full length nature of some of them has not been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001368882.1

Inheritance

ClinVar variants

P:48U:243B:156

Top phenotype

Myasthenic syndrome, congenital, 19

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr10:69,801,880-69,964,275

External References & Databases

Ensembl (ENSG00000197467)

Transcript & Mutation Effects

hg38 • Region Span ~162.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital myasthenic syndrome 19STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014745

Submitter: G2P

congenital myasthenic syndrome 19STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014745

Submitter: Labcorp Genetics (formerly Invitae)

congenital myasthenic syndrome 19STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014745

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Myasthenic syndrome, congenital, 19AR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: Musculoskeletal

Rationale: Individuals are affected by muscular weakness, including affecting the respiratory system, and medical management (with 3,4-diaminopyridine and salbutamol) has been reported as beneficial

Refs: 26626625

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COL13A1 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 619

Inborn genetic diseasesTotal: 125

Congenital myasthenic syndrome 19Total: 55

COL13A1-related disorderTotal: 47

not specifiedTotal: 27

COL13A1-related disordersTotal: 3

Pancreatic agenesis 2Total: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001368882.1. 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			6 clinvar	135 clinvar	5 clinvar	146
missense	1 clinvar		218 clinvar	10 clinvar	5 clinvar	234
nonsense	5 clinvar	4 clinvar	1 clinvar			10
start loss						0
frameshift	10 clinvar	4 clinvar	1 clinvar			15
splice donor/acceptor (+/-2bp)	1 clinvar	23 clinvar	17 clinvar	1 clinvar		42
Total	17	31	243	146	10	447

Highest pathogenic variant AF is 0.00014936924

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 76 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001368882.1	RefSeq	NP_001355811.1	41	MANE Select
ENST00000645393.2	Ensembl	ENSP00000496051.1	41	MANE Select
NM_001130103.2	RefSeq	NP_001123575.1	40	Standard
NM_001320951.2	RefSeq	NP_001307880.1	38	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein digestion and absorption - Homo sapiens (human)
Vitamin D Receptor Pathway
Collagen chain trimerization
Collagen biosynthesis and modifying enzymes
Integrin cell surface interactions

Biological Process

morphogenesis of a branching structure
endochondral ossification
cell-matrix adhesion
cell differentiation
extracellular matrix organization

Molecular Function

extracellular matrix structural constituent
protein binding
heparin binding
extracellular matrix structural constituent conferring tensile strength

Cellular Component

extracellular region
collagen type XIII trimer
extracellular space
endoplasmic reticulum lumen
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398978
Coding exons: 39
Length: 162388
Individuals with no LoFs: 124458
Homozygous LoFs: 0
Heterozygous LoFs: 218
Defined: 124676
p: 0.000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.770	364	408	0.893	0.0000226	4405
Missense (PolyPhen)		238	273.89	0.86895		2905
Synonymous	-1.23	168	149	1.13	0.00000851	1498
Loss of Function	3.05	31	55.6	0.558	0.00000255	684

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00019	rare
Latino/Admixed American	0.0050	0.0049	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00040	0.00039	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00013	0.00013	rare
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in cell-matrix and cell-cell adhesion interactions that are required for normal development. May participate in the linkage between muscle fiber and basement membrane. May play a role in endochondral ossification of bone and branching morphogenesis of lung. Binds heparin. At neuromuscular junctions, may play a role in acetylcholine receptor clustering (PubMed:26626625). {ECO:0000250|UniProtKB:Q9R1N9, ECO:0000269|PubMed:10865988, ECO:0000269|PubMed:11956183, ECO:0000269|PubMed:26626625}.;

Recessive Scores

pRec: 0.149

Intolerance Scores

LoFtool: 0.0355
RVIS EVS: -0.44
RVIS percentile EVS: 24.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.205

Gene Damage Prediction

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