CD151

protein-coding

CD151 molecule (Raph blood group), the group of Tetraspanins|CD molecules|Blood group antigens

Gene summary

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins and other transmembrane 4 superfamily proteins. It is involved in cellular processes including cell adhesion and may regulate integrin trafficking and/or function. This protein enhances cell motility, invasion and metastasis of cancer cells. Multiple alternatively spliced transcript variants that encode the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004357.5

Inheritance

AR, BG

ClinVar variants

P:9U:109B:47

Top phenotype

Raph blood group

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr11:832,887-839,831

External References & Databases

Ensembl (ENSG00000177697)

Transcript & Mutation Effects

hg38 • Region Span ~6.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epidermolysis bullosa simplex 7, with nephropathy and deafnessSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012190

Submitter: Orphanet

epidermolysis bullosa simplex 7, with nephropathy and deafnessMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0012190

Submitter: Genomics England PanelApp

epidermolysis bullosa simplex 7, with nephropathy and deafnessLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0012190

Submitter: Labcorp Genetics (formerly Invitae)

epidermolysis bullosa simplex 7, with nephropathy and deafnessSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012190

Submitter: G2P

Clinical Genomic Database (CGD)

Raph blood groupBG

Manifestation: Audiologic/Otolaryngologic; Dermatologic; Hematologic; Renal

Intervention: Hematologic

Rationale: Variants associated with a blood group may be important in specific situations (eg, related to transfusion)

Comments: Individuals with Nephropathy with pretibial epidermolysis bullosa and deafness may manifest with deafness, but it is described as typically postlingual

Refs: 3604155; 3238950; 3412548; 15265795; 18522704

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CD151 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 182

Epidermolysis bullosa simplex 7, with nephropathy and deafnessTotal: 58

RAPH BLOOD GROUP SYSTEMTotal: 50

Inborn genetic diseasesTotal: 33

CD151-related disorderTotal: 26

not specifiedTotal: 18

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004357.5. 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			6 clinvar	41 clinvar	1 clinvar	48
missense			92 clinvar	5 clinvar		97
nonsense	1 clinvar	3 clinvar	5 clinvar			9
start loss			1 clinvar			1
frameshift	1 clinvar	2 clinvar	1 clinvar			4
splice donor/acceptor (+/-2bp)		2 clinvar	4 clinvar			6
Total	2	7	109	46	1	165

Highest pathogenic variant AF is 0.000010954237

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 103 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004357.5	RefSeq	NP_004348.2	7	MANE Select
ENST00000397420.9	Ensembl	ENSP00000380565.3	7	MANE Select
NM_001039490.2	RefSeq	NP_001034579.1	7	Standard
NM_139029.2	RefSeq	NP_620598.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Primary Focal Segmental Glomerulosclerosis FSGS
Assembly of collagen fibrils and other multimeric structures
Alpha6Beta4Integrin
Collagen formation
Extracellular matrix organization

Biological Process

cell adhesion
cell surface receptor signaling pathway
positive regulation of cell migration
hemidesmosome assembly
T cell proliferation

Molecular Function

integrin binding
protein binding

Cellular Component

basement membrane
cytosol
plasma membrane
integral component of plasma membrane
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397420
Coding exons: 7
Length: 6989
Individuals with no LoFs: 125228
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125249
p: 0.0000838

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.594	135	156	0.866	0.00000927	1639
Missense (PolyPhen)		33	45.49	0.72543		523
Synonymous	-1.85	84	65.0	1.29	0.00000407	497
Loss of Function	1.32	10	15.6	0.641	8.34e-7	160

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential for the proper assembly of the glomerular and tubular basement membranes in kidney. {ECO:0000269|PubMed:15265795}.;
Disease: DISEASE: Nephropathy with pretibial epidermolysis bullosa and deafness (NPEBD) [MIM:609057]: A disorder characterized by the association of hereditary nephritis, epidermolysis bullosa, deafness, and beta-thalassemia minor. {ECO:0000269|PubMed:15265795}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.249

Intolerance Scores

LoFtool: 0.272
RVIS EVS: -0.36
RVIS percentile EVS: 28.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: E
Indispensability score: 0.802

Gene Damage Prediction

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