CD6

Chr 11

CD6 molecule

Also known as: TP120

NCBI Gene: 923 ENSG00000013725 UniProt: P30203

CD6 encodes a cell adhesion molecule on T-lymphocytes that mediates cell-cell contacts, regulates T-cell activation and proliferation through interaction with ALCAM/CD166, and functions as a pattern recognition receptor that binds bacterial components to trigger inflammatory responses. This gene is highly tolerant to loss-of-function variants and has been associated with susceptibility to multiple sclerosis, though definitive Mendelian disease associations in pediatric patients are not established from the available data.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein found on the outer membrane of T-lymphocytes as well as some other immune cells. The encoded protein contains three scavenger receptor cysteine-rich (SRCR) domains and a binding site for an activated leukocyte cell adhesion molecule. The gene product is important for continuation of T cell activation. This gene may be associated with susceptibility to multiple sclerosis (PMID: 19525953, 21849685). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.66

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.000

Z-score 3.00

OE 0.40 (0.26–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.91Z-score

OE missense 0.71 (0.64–0.79)

253 obs / 354.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.26–0.66)

0≤0.351.4

Missense OE?0.71 (0.64–0.79)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 12 / 29.6Missense obs/exp: 253 / 354.1Syn Z: 0.69

Background carrier burden — how many people carry a rare variant somewhere in CD6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 93

822 rare PASS variants

Rare truncating (LoF)

1 in 1,500

133 rare PASS variants

Rare synonymous (reference)

1 in 120

401 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CD6. 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 120	1 in 2,200
South Asian	~43k	1 in 85	1 in 2,100
Remaining (unassigned)	~30k	1 in 78	1 in 1,200
European (Finnish)	~27k	1 in 240	1 in 3,200
Admixed American	~22k	1 in 77	1 in 950
African / African American	~21k	1 in 99	1 in 1,200
East Asian	~20k	1 in 110	1 in 1,600
Ashkenazi Jewish	~13k	1 in 370	1 in 660
Middle Eastern	~2,884	1 in 73	≈ 1 in 630

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): 12 of 13 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: 12 of 13 (exon 10 below).? see exons ↓