CD5

Summary

CD5 (CD5 molecule, HGNC:1685) is a protein-coding gene on chromosome 11q12.2, encoding T-cell surface glycoprotein CD5 (P06127). Lymphoid-specific receptor expressed by all T-cells and in a subset of B-cells known as B1a cells.

This gene encodes a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Members of this family are secreted or membrane-anchored proteins mainly found in cells associated with the immune system. This protein is a type-I transmembrane glycoprotein found on the surface of thymocytes, T lymphocytes and a subset of B lymphocytes. The encoded protein contains three SRCR domains and may act as a receptor to regulate T-cell proliferation. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 921 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 72 total
• GTEx eGene: eQTL in 28 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 2 curated mechanism-of-action drugs
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.83 (unconstrained)
• MANE Select transcript: NM_014207
• Interaction hub: 2,069 STRING partners (top 7% of genes corpus-wide)
• Notable: 72 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1685
Approved symbol	CD5
Name	CD5 molecule
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	T1
Ensembl gene	ENSG00000110448
Ensembl biotype	protein_coding
OMIM	153340
Entrez	921

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

MANE Select: ENST00000347785

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 4: 1

ENST00000347785, ENST00000544014, ENST00000897878, ENST00001141147

RefSeq mRNA: 2 — MANE Select: NM_014207 NM_001346456, NM_014207

CCDS: CCDS8000

Canonical transcript exons

ENST00000347785 — 11 exons

Exon	Start	End
ENSE00000721687	61123884	61123937
ENSE00001119061	61118915	61118977
ENSE00001119062	61119234	61119575
ENSE00001145383	61122907	61123032
ENSE00001145387	61121611	61121904
ENSE00001145399	61118175	61118480
ENSE00001145405	61102489	61102615
ENSE00001145421	61115056	61115094
ENSE00001198934	61125032	61125151
ENSE00001198984	61125751	61125841
ENSE00001397719	61126288	61127852

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 93.15.

FANTOM5 (CAGE): breadth broad, TPM avg 14.3192 / max 942.2733, expressed in 220 samples.

Highest expression (Bgee): granulocyte, lymph node, blood, vermiform appendix, caecum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CD5 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 28 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 28 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	4.5e-95	-1.12	11:61146128:C:T
Muscle Skeletal	eqtl	2.8e-56	-0.74	11:61128693:T:C
Brain Cerebellar Hemisphere	eqtl	5.0e-35	-0.98	11:61128693:T:C
Nerve Tibial	eqtl	1.4e-28	-0.50	11:61147762:A:T
Brain Cerebellum	eqtl	7.1e-26	-0.92	11:61128693:T:C
Skin Sun Exposed Lower leg	eqtl	5.9e-25	-0.40	11:61128693:T:C
Pancreas	eqtl	6.5e-20	-0.72	11:61136611:G:GGTCA
Esophagus Muscularis	eqtl	1.2e-19	-0.51	11:61157266:T:C
Pituitary	eqtl	2.2e-18	-0.59	11:61152282:G:A
Artery Tibial	eqtl	5.3e-18	-0.33	11:61143649:T:C
Esophagus Gastroesophageal Junction	eqtl	5.3e-16	-0.58	11:61147762:A:T
Ovary	eqtl	6.1e-15	-0.79	11:61143649:T:C
Skin Not Sun Exposed Suprapubic	eqtl	9.5e-15	-0.31	11:61146084:G:C
Colon Sigmoid	eqtl	5.8e-12	-0.41	11:61143268:T:A
Stomach	eqtl	3.6e-11	-0.26	11:61145368:C:T
Breast Mammary Tissue	eqtl	4.3e-10	-0.27	11:61152282:G:A
Adipose Subcutaneous	eqtl	4.7e-09	-0.21	11:61132295:A:G
Prostate	eqtl	1.8e-08	-0.37	11:61136611:G:GGTCA
Uterus	eqtl	2.0e-07	-0.68	11:61127020:G:T
Heart Left Ventricle	eqtl	1.0e-05	-0.34	11:61157424:C:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
114545	13.8388	217
114546	0.4804	87

Top tissues by expression

showing 100 of 278 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.15	gold quality
lymph node	UBERON:0000029	88.68	gold quality
blood	UBERON:0000178	85.79	gold quality
vermiform appendix	UBERON:0001154	84.37	gold quality
caecum	UBERON:0001153	82.92	gold quality
tonsil	UBERON:0002372	79.59	gold quality
epithelium of nasopharynx	UBERON:0001951	79.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.92	gold quality
tongue squamous epithelium	UBERON:0006919	78.09	gold quality
spleen	UBERON:0002106	77.40	gold quality
mucosa of urinary bladder	UBERON:0001259	77.27	gold quality
bone marrow cell	CL:0002092	76.99	gold quality
diaphragm	UBERON:0001103	76.98	gold quality
cerebellar vermis	UBERON:0004720	76.59	gold quality
bone marrow	UBERON:0002371	75.81	gold quality
gall bladder	UBERON:0002110	75.03	gold quality
thymus	UBERON:0002370	74.73	silver quality
gingival epithelium	UBERON:0001949	74.50	gold quality
ileal mucosa	UBERON:0000331	74.34	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.20	gold quality
vena cava	UBERON:0004087	74.18	gold quality
cardia of stomach	UBERON:0001162	74.16	gold quality
saphenous vein	UBERON:0007318	73.68	gold quality
tongue	UBERON:0001723	73.50	silver quality
nipple	UBERON:0002030	73.49	gold quality
superficial temporal artery	UBERON:0001614	73.41	gold quality
subthalamic nucleus	UBERON:0001906	73.37	gold quality
ventral tegmental area	UBERON:0002691	73.26	gold quality
body of tongue	UBERON:0011876	73.25	gold quality
superior surface of tongue	UBERON:0007371	73.23	silver quality
pharyngeal mucosa	UBERON:0000355	73.14	gold quality
inferior vagus X ganglion	UBERON:0005363	73.06	gold quality
sperm	CL:0000019	73.02	gold quality
pericardium	UBERON:0002407	73.02	gold quality
substantia nigra pars reticulata	UBERON:0001966	72.99	gold quality
lateral globus pallidus	UBERON:0002476	72.89	gold quality
substantia nigra pars compacta	UBERON:0001965	72.76	gold quality
lateral nuclear group of thalamus	UBERON:0002736	72.74	gold quality
pylorus	UBERON:0001166	72.72	gold quality
pons	UBERON:0000988	72.70	gold quality
trachea	UBERON:0003126	72.62	gold quality
male germ cell	CL:0000015	72.33	gold quality
dorsal plus ventral thalamus	UBERON:0001897	72.26	gold quality
superior vestibular nucleus	UBERON:0007227	72.22	gold quality
renal medulla	UBERON:0000362	72.14	gold quality
synovial joint	UBERON:0002217	72.12	gold quality
dorsal root ganglion	UBERON:0000044	72.09	gold quality
trigeminal ganglion	UBERON:0001675	72.09	gold quality
penis	UBERON:0000989	71.55	gold quality
layer of synovial tissue	UBERON:0007616	71.49	gold quality
triceps brachii	UBERON:0001509	71.34	gold quality
gluteal muscle	UBERON:0002000	71.30	gold quality
medulla oblongata	UBERON:0001896	71.29	gold quality
cervix epithelium	UBERON:0004801	71.17	gold quality
gingiva	UBERON:0001828	71.10	gold quality
urethra	UBERON:0000057	71.07	gold quality
quadriceps femoris	UBERON:0001377	70.52	gold quality
orbitofrontal cortex	UBERON:0004167	70.41	gold quality
vastus lateralis	UBERON:0001379	70.35	gold quality
colonic epithelium	UBERON:0000397	70.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	69.90	gold quality
upper arm skin	UBERON:0004263	69.66	gold quality
small intestine	UBERON:0002108	69.22	gold quality
squamous epithelium	UBERON:0006914	68.81	gold quality
germinal epithelium of ovary	UBERON:0001304	68.69	gold quality
tibia	UBERON:0000979	68.68	gold quality
rectum	UBERON:0001052	68.39	gold quality
mammary duct	UBERON:0001765	68.07	gold quality
mucosa of paranasal sinus	UBERON:0005030	67.91	gold quality
amniotic fluid	UBERON:0000173	67.75	gold quality
endothelial cell	CL:0000115	67.72	gold quality
deltoid	UBERON:0001476	67.64	gold quality
decidua	UBERON:0002450	67.47	gold quality
tibialis anterior	UBERON:0001385	67.30	silver quality
secondary oocyte	CL:0000655	67.23	gold quality
pancreatic ductal cell	CL:0002079	67.14	silver quality
islet of Langerhans	UBERON:0000006	66.89	gold quality
mucosa of transverse colon	UBERON:0004991	66.89	gold quality
cervix squamous epithelium	UBERON:0006922	66.89	gold quality
epithelial cell of pancreas	CL:0000083	66.86	gold quality
type B pancreatic cell	CL:0000169	66.79	gold quality
nasal cavity epithelium	UBERON:0005384	66.70	gold quality
epithelium of mammary gland	UBERON:0003244	66.65	gold quality
epithelium of esophagus	UBERON:0001976	66.50	gold quality
skeletal muscle tissue	UBERON:0001134	65.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.56	gold quality
hair follicle	UBERON:0002073	65.44	gold quality
upper lobe of left lung	UBERON:0008952	65.15	gold quality
esophagus squamous epithelium	UBERON:0006920	65.01	gold quality
muscle tissue	UBERON:0002385	64.74	gold quality
upper lobe of lung	UBERON:0008948	64.34	gold quality
jejunum	UBERON:0002115	64.22	gold quality
saliva-secreting gland	UBERON:0001044	64.09	gold quality
urinary bladder	UBERON:0001255	64.02	gold quality
mouth mucosa	UBERON:0003729	63.65	gold quality
nasal cavity mucosa	UBERON:0001826	63.58	gold quality
lung	UBERON:0002048	63.52	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	63.46	gold quality
olfactory bulb	UBERON:0002264	63.36	gold quality
cartilage tissue	UBERON:0002418	63.36	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-70580	yes	361.46
E-CURD-122	yes	41.49
E-ANND-3	yes	9.81

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	43.3
Lymph node	tissue	35.5	high
Appendix	tissue	21.3	medium
Tonsil	tissue	20.8	high
Spleen	tissue	13.3	high
Bone marrow	tissue	11.6	medium
Stomach 1	tissue	7.4	not detected
Salivary gland	tissue	6.1	not detected
Urinary bladder	tissue	5.8	not detected
Lung	tissue	5.4	not detected
Gallbladder	tissue	4.6	not detected
Small intestine	tissue	3.5	not detected
Duodenum	tissue	2.9	not detected
Colon	tissue	2.7	not detected
Rectum	tissue	2.5	not detected
Basal ganglia	tissue	2.2	not detected
Esophagus	tissue	2.1	not detected
Nucleus accumbens	tissue	1.9
Retina	tissue	1.7
Hippocampus	tissue	1.7	not detected
Postcentral gyrus	tissue	1.7
Putamen	tissue	1.5
Liver	tissue	1.4	not detected
Ventral forebrain	tissue	1.4
Skin 1	tissue	1.3	not detected
Adipose tissue	tissue	1.3	not detected
Locus coeruleus	tissue	1.3
Smooth muscle	tissue	1.1	not detected
Choroid plexus	tissue	1.0
Spinal cord	tissue	1.0
Cervix	tissue	0.9	not detected
Breast	tissue	0.9	not detected
Prostate	tissue	0.9	not detected
Adrenal gland	tissue	0.9	not detected
Heart muscle	tissue	0.8	not detected
Vagina	tissue	0.8	not detected
Endometrium 1	tissue	0.7	not detected
Substantia nigra	tissue	0.7
Fallopian tube	tissue	0.7	not detected
Testis	tissue	0.6	medium
Skeletal muscle	tissue	0.6	not detected
Medulla oblongata	tissue	0.5
Thalamus	tissue	0.5
Superior colliculi	tissue	0.5
Corpus callosum	tissue	0.5
Olfactory bulb	tissue	0.5
Pituitary gland	tissue	0.4
Pons	tissue	0.4
Ovary	tissue	0.4	not detected
Epididymis	tissue	0.4	not detected
Midbrain	tissue	0.4
Thyroid gland	tissue	0.4	not detected
Periaqueductal gray	tissue	0.4
Septum	tissue	0.4
Cerebral cortex	tissue	0.3	not detected
Seminal vesicle	tissue	0.3	not detected
Tongue	tissue	0.3
Hypothalamus	tissue	0.3
Placenta	tissue	0.3	not detected
Kidney	tissue	0.3	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Hippocampus, CA3 (2.6), Reticular pontine nucleus, oral (2.5), Dentate gyrus (2.4), Stria terminalis, bed nucleus (2.4), Arcuate nucleus (2.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, GATA3, GLI3, MYC, NFATC1, TCF3, TFAP2A

miRNA regulators (miRDB)

Targeting CD5 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 36 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-3132	97.96	67.91	711
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-625-3P	97.32	66.55	554
HSA-MIR-197-5P	97.23	68.10	596
HSA-MIR-1306-5P	97.11	64.04	755

Functional genomics

gnomAD constraint: pLI 1.25e-07, LOEUF 0.835, missense Z 1.35 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000347785 — one region, missense o/e 0.86.

Literature-anchored findings (GeneRIF, showing 40)

• CD5-negative regulation of B cell receptor signaling originates from tyrosine residue Y429 outside an immunoreceptor tyrosine-based inhibitory motif (PMID:11751967)
• Origins and functions of B-1 cells with notes on the role of CD5. Review. (PMID:11861604)
• multiple somatic mutations in human cancers. the value of the CD5 microsatellite as a marker for instability in different tumor types, particularly in B-cell leukemia and lymphoma. (PMID:11869933)
• CD5 supports the survival of B cells by stimulating IL-10 production and by concurrently exerting negative feedback on BCR-induced signaling events that can promote cell death. (PMID:12393419)
• CD5-negative, CD10-negative small B-cell leukemia: variant of chronic lymphocytic leukemia or a distinct entity (PMID:12447961)
• CD5 is rapidly recruited at the immunological synapse (IS) and lowers the T cell response elicited by antigen presentation by targeting downstream signaling events without affecting IS formation. (PMID:12707340)
• The CD5+ diffuse large-B-cell lymphoma (DLBCL) constitutes a disease category distinct from that of CD5- DLBCL and other CD5+ malignancies. (PMID:14603444)
• the 5’-flanking region of human CD5 is transcriptionally active in T cells, and Ets transcription factors in conjunction with other regulatory elements are responsible for constitutive and tissue-specific CD5 expression (PMID:15187131)
• Overexpression in these cells indicates diseaase progression in B=cell leukemia patients. (PMID:15549146)
• CD5 is associated with receptor revision in activated mature B cells and likely to promote expression of suitable immunoglobulin gene receptors capable of initiating the germinal center reaction. (PMID:15843554)
• The polymorphic CD5 promoter is associated with increased susceptibility to B-cell chronic lymphocytic leukemia and mantle cell lymphoma. (PMID:15981803)
• balance between the 2 alternative exons 1 might be central to the regulation of membrane CD5 in human B cells (PMID:15998834)
• analysis of CD5-positive diffuse large B-cell lymphoma with the unusual phenotype of cytoplasmic CD20 (+), surface CD20 (-) [case report] (PMID:16923582)
• CD5 does not inhibit properly the BCR-mediated signaling in leukemic cells. (PMID:17325858)
• T lymphocyte activation-induced cell death (AICD) in response to a cognate tumor is inversely proportional to the surface expression level of CD5. (PMID:17513730)
• a decrease in CD22(+) B cells and increase in CD5(+)CD22(-) B cells play critical roles in the pathogenesis of RA mediated by the activation of B cells (PMID:17585360)
• support a model where chronic lymphocytic leukemia cells are chronically stimulated, leading to CD5 activation and cell survival (PMID:17878328)
• 3D solution structure of a non-glycosylated double mutant of the N-terminal domain of human CD5 was presented. (PMID:18339402)
• CD5 positive diffuse large B-cell lymphoma frequently express BCL2 protein and show that it is mainly included in the non-germinal center B-cell type of this cancer. (PMID:18556402)
• Report CD5-undetected by immunohistochemistry in a t(11;14)(q13;q32)-positive conjunctival mantle cell lymphoma. (case report) (PMID:18572329)
• diminishes the threshold of the response by cells expressing CD5 (PMID:18641338)
• present results indicate that the CD5 lymphocyte receptor may sense the presence of conserved fungal components [namely, (1–>3)-beta-d-glucans] and support the therapeutic potential of soluble CD5 forms in fungal sepsis (PMID:19141631)
• Data indicate that E1B-CD5-expressing B cells have the capacity to interfere with the immune response through their ability to produce high levels of IL-10. (PMID:19758163)
• Type B3 thymic epithelial tumor in an adolescent detected by immunohistochemical staining for CD5, CD99, and KIT (CD117): a case report. (PMID:19901887)
• CD5-positive splenic marginal zone lymphoma may be related to memory B-cell neoplasm or plasma cell differentiation (PMID:21123968)
• full-length protein variant, encoded by E1A-cd5, translocates the phosphatase SHP-1 to the vicinity of the B-cell receptor, raises its threshold, and thereby limits the response of autoreactive B cells [review] (PMID:21395509)
• Data show that CD5 expression is associated with NFAT2 activity and mildly STAT3 activity, indicating that CD5 controls IL-10 secretion. (PMID:21398617)
• Conclude that high percentages of CD5+B cells independently associate with increased risk of early conversion to multiple sclerosis in clinically isolated syndrome patients. (PMID:21436320)
• Post-thymic regulation of CD5 levels in human memory T cells is inversely associated with the strength of responsiveness to interleukin-15. (PMID:21539877)
• CD5 glycoprotein-mediated T cell inhibition dependent on inhibitory phosphorylation of Fyn kinase (PMID:21757751)
• immunological significance of CD19 for the IL-10 production by CD5(+) B cells (PMID:21786452)
• The primary carcinoma showing thymus-like elements of the thyroid frequently expresses KIT and CD5 proteins. (PMID:21835435)
• Case Report: describe the recurrence of CD5 positive MALT lymphoma in the oral cavity and compared the immunohistochemical expressions of CD5, lambda, and kappa between the primary and recurrent tumors. (PMID:21892966)
• Alternative costimulation via CD5, rather than classic costimulation via CD28, primes naive T cells for stable Th17 development through promoting the expression of IL-23R. (PMID:21926348)
• Hepatitis C virus infection of human T lymphocytes is mediated by CD5. (PMID:22278227)
• Case Report: CD5-positive marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) of the lung. (PMID:22333190)
• Bcl-2 and CD5 are associated in non-Hodgkin lymphoma of head and neck and may be markers of poor prognosis, while Bcl-6 is positive especially in the tumor forms associated with the predominance of small cells and is a marker of favorable prognosis (PMID:22395507)
• Our results show that CD5 expression is rare in MALT lymphoma, and is often associated with nongastric disease and an increased tendency to present with disseminated disease. (PMID:22406370)
• Our results indicate that CD5(+) B cell subsets might be associated with pathogenesis of SPMS. (PMID:22732449)
• Functional CD5-dependent casein kinase 2 signaling is necessary in a CD5 knock-in mouse for efficient differentiation of naive CD4+ T cells into T helper (Th)2 and Th17 cells, but not Th1-type cells. (PMID:22904299)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-14d8.20	ENSDARG00000045837
danio_rerio	si:ch211-150o23.3	ENSDARG00000078502
mus_musculus	Cd5	ENSMUSG00000024669
rattus_norvegicus	Cd5	ENSRNOG00000020872
drosophila_melanogaster	Loxl2	FBGN0034660

Paralogs (15): CD6 (ENSG00000013725), CD5L (ENSG00000073754), LGALS3BP (ENSG00000108679), LOX (ENSG00000113083), LOXL3 (ENSG00000115318), LOXL1 (ENSG00000129038), LOXL2 (ENSG00000134013), LOXL4 (ENSG00000138131), SSC4D (ENSG00000146700), PRSS12 (ENSG00000164099), CD163 (ENSG00000177575), CD163L1 (ENSG00000177675), SSC5D (ENSG00000179954), DMBT1 (ENSG00000187908), SCART1 (ENSG00000214279)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88340) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 17 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal spleen morphology	1
enlarged spleen	1
abnormal uterus morphology	1
abnormal skin morphology	1
abnormal T cell physiology	1
decreased susceptibility to experimental autoimmune encephalomyelitis	1
increased spleen weight	1
increased regulatory T cell number	1
decreased B cell number	1
increased double-negative T cell number	1
decreased double-positive T cell number	1
decreased T cell proliferation	1
increased T cell proliferation	1
decreased CD4-positive, alpha-beta T cell number	1
decreased follicular B cell number	1
abnormal T cell anergy	1
decreased T-helper 17 cell number	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P19238	61.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC02954	ncRNA	123466205
VPS37C	protein-coding	55048
CD6	protein-coding	923
PGA3	protein-coding	643834
PGA4	protein-coding	643847

Protein

Protein identifiers

T-cell surface glycoprotein CD5 — P06127 (reviewed: P06127)

Alternative names: Lymphocyte antigen T1/Leu-1

All UniProt accessions (2): F5GYK3, P06127

UniProt curated annotations — full annotation on UniProt →

Function. Lymphoid-specific receptor expressed by all T-cells and in a subset of B-cells known as B1a cells. Plays a role in the regulation of TCR and BCR signaling, thymocyte selection, T-cell effector differentiation and immune tolerance. Acts by interacting with several ligands expressed on B-cells such as CD5L or CD72 and thereby plays an important role in contact-mediated, T-dependent B-cell activation and in the maintenance of regulatory T and B-cell homeostasis. Functions as a negative regulator of TCR signaling during thymocyte development by associating with several signaling proteins including LCK, CD3Z chain, PI3K or CBL. Mechanistically, co-engagement of CD3 with CD5 enhances phosphorylated CBL recruitment leading to increased VAV1 phosphorylation and degradation. Modulates B-cell biology through ERK1/2 activation in a Ca(2+)-dependent pathway via the non-selective Ca(2+) channel TRPC1, leading to IL-10 production.

Subunit / interactions. Interacts with CD72/LYB-2. Interacts with PTPN6/SHP-1. Interacts with CBL. Interacts with CD5L. Interacts with CD3Z/CD247.

Subcellular location. Cell membrane.

Post-translational modifications. Phosphorylated on serine, threonine and tyrosine residues following TCR stimulation. Phosphorylated by LCK on Tyr-453 and Tyr-487 upon TCR engagement.

RefSeq proteins (2): NP_001333385, NP_055022* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001190	SRCR	Domain
IPR003566	Tcell_CD5	Family
IPR036772	SRCR-like_dom_sf	Homologous_superfamily

Pfam: PF00530

UniProt features (59 total): strand 18, disulfide bond 10, modified residue 5, helix 4, region of interest 3, sequence variant 3, domain 3, compositionally biased region 2, glycosylation site 2, topological domain 2, mutagenesis site 2, signal peptide 1, chain 1, transmembrane region 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
2JA4	Crystal structure of CD5 domain III reveals the fold of a group B scavenger cysteine-rich …	X-RAY DIFFRACTION	2.21
2OTT	Crystal structure of CD5_DIII	X-RAY DIFFRACTION	2.5
2JOP	Solution structure of the N-terminal extracellular domain of the lymphocyte receptor CD5 …	SOLUTION NMR
2JP0	Solution structure of the N-terminal extraceullular domain of the lymphocyte receptor CD5 …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06127-F1	73.32	0.32

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5)

Type	Positions
Phosphoserine	439, 460, 483, 485
Phosphotyrosine	453

Disulfide bonds (10)

Type	Positions
Disulfide bond	44–86, 60–125, 81–132, 107–117, 201–267, 244–250, 285–321, 301–360, 316–367, 342–350

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	116, 241

Mutagenesis-validated functional residues (2)

Position	Phenotype
446–447	no loss of erk1/2 activation and il-10 production.
452–454	strong reduction of erk1/2 activation and il-10 production.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 250 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_REGULATION_OF_B_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, MODULE_64, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_LYMPHOCYTE_COSTIMULATION, GOCC_CELL_SURFACE, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75, SHANK_TAL1_TARGETS_DN, GOBP_APOPTOTIC_SIGNALING_PATHWAY, MODULE_171

GO Biological Process (3): cell recognition (GO:0008037), T cell costimulation (GO:0031295), negative regulation of B cell receptor signaling pathway (GO:0050859)

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

GO top-level categories

14 GO namespaces:

Category	Terms
cellular process	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
B cell receptor signaling pathway	1
regulation of B cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 8 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of B cell receptor signaling pathway	BP	direct assay
plasma membrane	CC	direct assay
signaling receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,069 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD5	CR2	P20023	914
CD5	CD8A	P01732	908
CD5	CD4	P01730	900
CD5	CD19	P15391	894
CD5	CD7	P09564	885
CD5	MME	P08473	883
CD5	CD2	P06729	881
CD5	SPN	P16150	859
CD5	TNFRSF8	P28908	857
CD5	PTPRC	P08575	857
CD5	BCL6	P41182	856
CD5	CD1D	P15813	830
CD5	CCND1	P24385	820
CD5	BCL2	P10415	814
CD5	CD79A	P11912	804

IntAct

Human interaction partners of CD5 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
PIK3R1	association	0.460	2
CD72	physical association	0.400	1
AP2M1	physical association	0.370	1
IDE	association	0.350	1
RASA1	association	0.350	1

BioGRID (22 interactions; top human partners by supporting records): CBL (Affinity Capture-Western; 2 records), ARL10 (Proximity Label-MS), CD2 (Affinity Capture-Western), CD6 (FRET), CD72 (Reconstituted Complex), CSNK2A1 (Biochemical Activity), EFNA1 (Affinity Capture-MS), FYN (Affinity Capture-Western), IDE (Affinity Capture-MS), LCK (Affinity Capture-Western), PPP1R7 (Affinity Capture-MS), PTPN6 (Affinity Capture-Western), RASA1 (Affinity Capture-Western), SPR (Affinity Capture-MS), USP11 (Affinity Capture-MS)

SIGNOR signaling

showing 8 of 16 signaling interactions:

A	Effect	B	Mechanism
LCK	“up-regulates activity”	CD5	phosphorylation
PRKCA	unknown	CD5	phosphorylation
PRKCG	unknown	CD5	phosphorylation
PRKCB	unknown	CD5	phosphorylation
CSNK2A1	up-regulates	CD5	phosphorylation
PRKCA	up-regulates	CD5	phosphorylation
PRKCG	up-regulates	CD5	phosphorylation
FYN	unknown	CD5	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for CD5: 72 ClinVar records (0 pathogenic / likely pathogenic); 17 GWAS associations.

ClinVar

72 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	4
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 670):

Position(s)	Effect	Δscore	Sites
11:61115095–61115096	donor_loss	1.0000	5
11:61118978–61118979	donor_loss	1.0000	4
11:61122905–61122906	acceptor_loss	1.0000	6
11:61123034	donor_loss	1.0000	2
11:61123877	acceptor_gain	1.0000
11:61123882–61123883	acceptor_loss	1.0000	6
11:61123939	donor_loss	1.0000	2
11:61125025	acceptor_gain	1.0000
11:61125030–61125031	acceptor_loss	1.0000	5
11:61125152–61125153	donor_loss	1.0000	4

AlphaMissense

589 missense substitutions predicted likely pathogenic (of 3,222 scored), across 174 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F251	8	0.880	0.985
C107	7	0.977	0.991
C267	7	0.968	0.987
C81	7	0.967	0.986
C201	7	0.961	0.986
C316	7	0.960	0.979
C132	7	0.959	0.979
C86	7	0.958	0.983
C285	7	0.958	0.980
C117	7	0.957	0.979
C342	7	0.950	0.967
W237	7	0.949	0.996
C367	7	0.947	0.972
C44	7	0.944	0.982
C350	7	0.944	0.974
C301	7	0.943	0.967
C321	7	0.942	0.980
C206	7	0.932	0.977
W297	7	0.932	0.998
W64	7	0.930	0.996

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Head and Neck Squamous Cell Carcinoma (TCGA)	favorable	6.45e-06
Lung Adenocarcinoma (TCGA)	favorable	0.000943

Disease associations

OMIM: gene MIM:153340 | disease phenotypes:

GWAS associations

17 associations:

Study	Trait	p-value
GCST001725_10	Inflammatory bowel disease	9e-13
GCST001198_59	Multiple sclerosis	2e-11
GCST006195_19	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3e-9
GCST005569_50	Rheumatoid arthritis	3e-8
GCST008526_9	Coffee consumption	1e-7
GCST003854_10	Gut microbiota (functional units)	2e-7
GCST005531_79	Multiple sclerosis	2e-7
GCST003854_47	Gut microbiota (functional units)	1e-6
GCST003855_17	Gut microbiota (bacterial taxa)	1e-6
GCST003855_18	Gut microbiota (bacterial taxa)	1e-6
GCST003855_19	Gut microbiota (bacterial taxa)	1e-6
GCST002318_75	Rheumatoid arthritis	3e-6
GCST006192_17	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3e-6
GCST006959_188	Rheumatoid arthritis	4e-6
GCST003854_35	Gut microbiota (functional units)	5e-6
GCST005568_22	Rheumatoid arthritis (ACPA-positive)	6e-6
GCST006048_13	Rheumatoid arthritis (ACPA-positive)	6e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006781	coffee consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712888 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the CD5 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

2 curated-mechanism drugs:

Drug	Modality	Max phase
TELIMOMAB ARITOX	Antibody drug conjugate	2
ZOLIMOMAB ARITOX	Antibody drug conjugate	2

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression	2
Lipopolysaccharides	decreases expression, increases expression, affects response to substance	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
(+)-JQ1 compound	decreases expression	1
Bortezomib	decreases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation	1
Diazinon	increases methylation	1
Malathion	decreases expression	1
Nickel	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5ZI	JOK-1/5.3	Cancer cell line	Male
CVCL_B8D4	Abcam HCT 116 CD5 KO	Cancer cell line	Male
CVCL_B9FB	Abcam A-549 CD5 KO	Cancer cell line	Male
CVCL_D2E9	Abcam MCF-7 CD5 KO	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.