CSPG4

Chr 15

chondroitin sulfate proteoglycan 4

Also known as: CSPG4A, HMW-MAA, MCSP, MCSPG, MEL-CSPG, MSK16, NG2

NCBI Gene: 1464 ENSG00000173546 UniProt: Q6UVK1 OMIM: 601172

A human melanoma-associated chondroitin sulfate proteoglycan plays a role in stabilizing cell-substratum interactions during early events of melanoma cell spreading on endothelial basement membranes. CSPG4 represents an integral membrane chondroitin sulfate proteoglycan expressed by human malignant melanoma cells. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.46

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.000

Z-score 5.13

OE 0.32 (0.23–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.41Z-score

OE missense 0.89 (0.85–0.94)

1244 obs / 1391.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.32 (0.23–0.46)

0≤0.351.4

Missense OE?0.89 (0.85–0.94)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 21 / 65.9Missense obs/exp: 1244 / 1391.7Syn Z: 0.65

Background carrier burden — how many people carry a rare variant somewhere in CSPG4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 15

2,756 rare PASS variants

Rare truncating (LoF)

1 in 680

250 rare PASS variants

Rare synonymous (reference)

1 in 27

1,339 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CSPG4. 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 18	1 in 810
South Asian	~43k	1 in 14	1 in 530
Remaining (unassigned)	~30k	1 in 14	1 in 210
European (Finnish)	~27k	1 in 43	1 in 910
Admixed American	~22k	1 in 16	1 in 620
African / African American	~21k	1 in 14	1 in 660
East Asian	~20k	1 in 15	1 in 870
Ashkenazi Jewish	~13k	1 in 69	1 in 1,000
Middle Eastern	~2,884	1 in 17	≈ 1 in 680

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): 9 of 10 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 10.? see exons ↓