CD6

protein-coding

CD6 molecule, the group of CD molecules|Scavenger receptor cysteine rich domain containing

Gene summary

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]

MANE transcript

NM_006725.5

Inheritance

—

ClinVar variants

U:92B:10

Top phenotype

CD6-related disorder

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr11:60,971,680-61,020,377

External References & Databases

Ensembl (ENSG00000013725)

Transcript & Mutation Effects

hg38 • Region Span ~48.7 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 CD6 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 89

CD6-related disorderTotal: 6

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006725.5. 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			2 clinvar	4 clinvar	1 clinvar	7
missense			89 clinvar	5 clinvar		94
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	92	9	1	102

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006725.5	RefSeq	NP_006716.3	13	MANE Select
ENST00000313421.11	Ensembl	ENSP00000323280.7	13	MANE Select
NM_001254750.2	RefSeq	NP_001241679.1	11	Standard
NM_001254751.2	RefSeq	NP_001241680.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)

Biological Process

immunological synapse formation
adaptive immune response
acute inflammatory response to antigenic stimulus
receptor-mediated endocytosis
heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules

Molecular Function

lipopolysaccharide binding
scavenger receptor activity
protein binding
identical protein binding
lipoteichoic acid binding

Cellular Component

immunological synapse
extracellular region
integral component of plasma membrane
external side of plasma membrane
intrinsic component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000313421
Coding exons: 13
Length: 48735
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 125748
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.91	253	354	0.715	0.0000196	4256
Missense (PolyPhen)		69	123.43	0.55904		1525
Synonymous	0.695	144	155	0.929	0.00000970	1344
Loss of Function	3.00	12	29.6	0.405	0.00000135	349

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cell adhesion molecule that mediates cell-cell contacts and regulates T-cell responses via its interaction with ALCAM/CD166 (PubMed:15048703, PubMed:15294938, PubMed:16352806, PubMed:16914752, PubMed:24945728, PubMed:24584089). Contributes to signaling cascades triggered by activation of the TCR/CD3 complex (PubMed:24584089). Functions as costimulatory molecule; promotes T-cell activation and proliferation (PubMed:15294938, PubMed:16352806, PubMed:16914752). Contributes to the formation and maturation of the immunological synapse (PubMed:15294938, PubMed:16352806). Functions as calcium-dependent pattern receptor that binds and aggregates both Gram-positive and Gram-negative bacteria. Binds both lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteichoic acid from Gram-positive bacteria (PubMed:17601777). LPS binding leads to the activation of signaling cascades and down-stream MAP kinases (PubMed:17601777). Mediates activation of the inflammatory response and the secretion of pro-inflammatory cytokines in response to LPS (PubMed:17601777). {ECO:0000269|PubMed:15048703, ECO:0000269|PubMed:15294938, ECO:0000269|PubMed:16352806, ECO:0000269|PubMed:16914752, ECO:0000269|PubMed:17601777, ECO:0000269|PubMed:24584089, ECO:0000269|PubMed:24945728}.;

Intolerance Scores

LoFtool: 0.584
RVIS EVS: 0.82
RVIS percentile EVS: 88.02

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.567

Gene Damage Prediction

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