CD151

Chr 11AR

CD151 molecule (Raph blood group)

Also known as: EBS7, GP27, MER2, PETA-3, RAPH, SFA1, TSPAN24

NCBI Gene: 977 ENSG00000177697 UniProt: P48509 OMIM: 602243

The CD151 protein is a tetraspanin that forms specialized membrane microdomains and regulates integrin signaling, facilitating cell adhesion, migration, and basement membrane assembly. Mutations cause epidermolysis bullosa simplex with nephropathy and deafness, a multisystem disorder affecting skin, kidneys, and hearing through autosomal recessive inheritance. The gene shows low constraint against loss-of-function variants (pLI near zero), consistent with recessive disease requiring biallelic mutations.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

[Blood group, Raph]MIM #179620

Epidermolysis bullosa simplex 7, with nephropathy and deafnessMIM #609057

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Epidermolysis bullosa simplex 7, with nephropathy and deafness; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.09

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — CD151

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.09LOEUF

pLI 0.000

Z-score 1.32

OE 0.64 (0.39–1.09)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.59Z-score

OE missense 0.87 (0.75–1.00)

135 obs / 155.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.39–1.09)

0≤0.351.4

Missense OE?0.87 (0.75–1.00)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 10 / 15.6Missense obs/exp: 135 / 155.9Syn Z: -1.85

Background carrier burden — how many people carry a rare variant somewhere in CD151?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

328 rare PASS variants

Rare truncating (LoF)

1 in 3,900

50 rare PASS variants

Rare synonymous (reference)

1 in 200

164 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CD151. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 250	1 in 4,600
South Asian	~43k	1 in 170	1 in 1,900
Remaining (unassigned)	~30k	1 in 120	≈ 1 in 10,000
European (Finnish)	~26k	1 in 840	1 in 4,400
Admixed American	~22k	1 in 180	1 in 2,200
African / African American	~21k	1 in 160	1 in 2,700
East Asian	~20k	1 in 150	≈ 1 in 4,000
Ashkenazi Jewish	~13k	1 in 480	none seen
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓