CD109

protein-coding

CD109 molecule, the group of CD molecules|C3 and PZP like, alpha-2-macroglobulin domain containing

Gene summary

This gene encodes a glycosyl phosphatidylinositol (GPI)-linked glycoprotein that localizes to the surface of platelets, activated T-cells, and endothelial cells. The protein binds to and negatively regulates signalling by transforming growth factor beta (TGF-beta). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

MANE transcript

NM_133493.5

Inheritance

—

ClinVar variants

U:235B:21

Top phenotype

Multiple sclerosis

gnomAD constraint

pLI —, LoF o/e 0.97

Max pathogenic AF

—

Genomic locus

chr6:73,695,785-73,828,316

External References & Databases

Ensembl (ENSG00000156535)

Transcript & Mutation Effects

hg38 • Region Span ~132.5 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 CD109 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 221

not providedTotal: 22

Multiple sclerosisTotal: 1

High myopiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_133493.5. 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			5 clinvar	1 clinvar	3 clinvar	9
missense			224 clinvar	13 clinvar	4 clinvar	241
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	235	14	7	256

Loading ClinVar variants...

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_133493.5	RefSeq	NP_598000.2	33	MANE Select
ENST00000287097.6	Ensembl	ENSP00000287097.4	33	MANE Select
NM_001159587.3	RefSeq	NP_001153059.1	33	Standard
NM_001159588.3	RefSeq	NP_001153060.1	32	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational modification: synthesis of GPI-anchored proteins
Post-translational protein modification
Metabolism of proteins
Platelet degranulation
Response to elevated platelet cytosolic Ca2+

Biological Process

negative regulation of protein phosphorylation
hair follicle development
platelet degranulation
negative regulation of keratinocyte proliferation
negative regulation of endopeptidase activity

Molecular Function

serine-type endopeptidase inhibitor activity
transforming growth factor beta binding

Cellular Component

extracellular region
extracellular space
plasma membrane
cell surface
platelet alpha granule membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000287097
Coding exons: 33
Length: 132533
Individuals with no LoFs: 125409
Homozygous LoFs: 2
Heterozygous LoFs: 337
Defined: 125748
p: 0.00135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.503	755	717	1.05	0.0000342	9426
Missense (PolyPhen)		183	157.96	1.1585		2136
Synonymous	0.459	253	262	0.964	0.0000130	2749
Loss of Function	0.221	68	70.0	0.972	0.00000325	917

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00093	0.00092	rare
Latino/Admixed American	0.0016	0.0016	notable
Ashkenazi Jewish	0.00090	0.00089	rare
East Asian	0.0019	0.0018	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0010	0.0010	notable
South Asian	0.0036	0.0034	notable
Other	0.00099	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Modulates negatively TGFB1 signaling in keratinocytes. {ECO:0000269|PubMed:16754747}.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 1.00
RVIS EVS: 4.68
RVIS percentile EVS: 99.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.356

Gene Damage Prediction

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