PTCRA

Summary

PTCRA (pre T cell antigen receptor alpha, HGNC:21290) is a protein-coding gene on chromosome 6p21.1, encoding Pre T-cell antigen receptor alpha (Q6ISU1). Component of the pre-T-cell receptor complex (composed of PTCRA, TCRB and the CD3 complex) that has a crucial role in early T-cell development, particularly alpha-beta T cell differentiation.

The protein encoded by this gene is a single-pass type I membrane protein that is found in immmature but not mature T-cells. Along with TCRB and CD3 complex, the encoded protein forms the pre-T-cell receptor complex, which regulates early T-cell development. Four transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 171558 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 126, susceptibility to (Strong, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 51 total — 1 pathogenic
• Phenotypes (HPO): 90
• MANE Select transcript: NM_138296

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21290
Approved symbol	PTCRA
Name	pre T cell antigen receptor alpha
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	PTA, PT-ALPHA
Ensembl gene	ENSG00000171611
Ensembl biotype	protein_coding
OMIM	606817
Entrez	171558

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000304672, ENST00000441198, ENST00000446507, ENST00000616441

RefSeq mRNA: 4 — MANE Select: NM_138296 NM_001243168, NM_001243169, NM_001243170, NM_138296

CCDS: CCDS4874, CCDS59019, CCDS59020, CCDS75457

Canonical transcript exons

ENST00000304672 — 4 exons

Exon	Start	End
ENSE00000000100	42916053	42916127
ENSE00000000101	42925261	42925838
ENSE00001175218	42924229	42924273
ENSE00001175224	42923027	42923347

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 94.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1473 / max 390.8996, expressed in 33 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67829	0.9498	31
67828	0.1348	11
203994	0.0627	8

Top tissues by expression

248 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	94.81	silver quality
olfactory bulb	UBERON:0002264	94.67	silver quality
monocyte	CL:0000576	93.83	gold quality
mononuclear cell	CL:0000842	93.70	gold quality
tongue squamous epithelium	UBERON:0006919	93.16	silver quality
leukocyte	CL:0000738	92.86	gold quality
vena cava	UBERON:0004087	92.67	gold quality
parotid gland	UBERON:0001831	91.89	gold quality
thymus	UBERON:0002370	90.61	gold quality
gluteal muscle	UBERON:0002000	90.45	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.18	silver quality
heart right ventricle	UBERON:0002080	87.83	silver quality
pancreatic ductal cell	CL:0002079	87.62	silver quality
body of tongue	UBERON:0011876	87.60	silver quality
inferior olivary complex	UBERON:0002127	87.15	gold quality
tendon of biceps brachii	UBERON:0008188	86.91	silver quality
pons	UBERON:0000988	86.74	silver quality
nasal cavity epithelium	UBERON:0005384	86.13	silver quality
diaphragm	UBERON:0001103	85.99	gold quality
tongue	UBERON:0001723	85.24	silver quality
cervix squamous epithelium	UBERON:0006922	85.18	silver quality
granulocyte	CL:0000094	85.13	gold quality
buccal mucosa cell	CL:0002336	84.95	gold quality
subthalamic nucleus	UBERON:0001906	84.63	silver quality
lateral nuclear group of thalamus	UBERON:0002736	84.63	silver quality
dorsal plus ventral thalamus	UBERON:0001897	84.59	silver quality
pericardium	UBERON:0002407	84.55	gold quality
cardia of stomach	UBERON:0001162	84.18	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	84.18	gold quality
pharyngeal mucosa	UBERON:0000355	84.05	silver quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-79	yes	2016.30
E-ANND-5	yes	586.99
E-HCAD-1	yes	16.27
E-MTAB-9221	yes	15.91
E-MTAB-6701	yes	13.77
E-CURD-122	yes	12.39
E-HCAD-10	yes	8.20
E-CURD-88	yes	4.29
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, IKZF1, NEUROD1, RBPJ, SPI1, TAL1, TCF12, TCF3

miRNA regulators (miRDB)

7 targeting PTCRA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-7106-3P	97.33	65.33	644
HSA-MIR-4264	96.35	64.76	1480

Literature-anchored findings (GeneRIF, showing 4)

• Combined expression of pTalpha and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis (PMID:11891328)
• High levels of pre-T cell receptor alpha-chain mRNA splice forms have been demonstrated in immature CD2+CD7+CD3- T cells of the jejunal mucosa, both intraepithelially and in lamina propria. (PMID:14500629)
• identified a polyproline-arginine sequence in the pTalpha cytoplasmic tail that interacted in vitro with SH3 domains of the CIN85/CMS family of adaptors, and mediated the recruitment of multiprotein complexes involving all (CMS, CIN85, and CD2BP3) members (PMID:17823309)
• Generation of self-reactive, shared T-cell receptor alpha chains in the human thymus. (PMID:33652347)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ptcra	ENSMUSG00000036858
rattus_norvegicus	Ptcra	ENSRNOG00000042581

Protein

Protein identifiers

Pre T-cell antigen receptor alpha — Q6ISU1 (reviewed: Q6ISU1)

Alternative names: pT-alpha-TCR

All UniProt accessions (2): A0A087WTE9, Q6ISU1

UniProt curated annotations — full annotation on UniProt →

Function. Component of the pre-T-cell receptor complex (composed of PTCRA, TCRB and the CD3 complex) that has a crucial role in early T-cell development, particularly alpha-beta T cell differentiation.

Subunit / interactions. Heterodimer with TCRB; disulfide linked. This heterodimer assembles with CD3 proteins into a signaling-competent pre-T-cell receptor complex. Interacts with RHBDD1.

Subcellular location. Membrane. Cell membrane.

Tissue specificity. Expressed in immature but not mature T-cells. Also found in CD34+ cells from peripheral blood, CD34+ precursors from umbilical cord blood and adult bone marrow.

Disease relevance. Immunodeficiency 126 (IMD126) [MIM:620931] An autosomal recessive immunologic disorder characterized by T-cell abnormalities with impaired development of alpha/beta T cells and increased susceptibility to recurrent infections. Disease severity is highly variable, ranging from life-threatening infections in infancy to severe infections, lymphoproliferation or autoimmunity beginning between the ages of 13 to 25 years. Some affected individuals may have very mild disease or be asymptomatic. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ISU1-1	1, pTalpha-1	yes
Q6ISU1-2	2, pTalpha-2
Q6ISU1-3	3

RefSeq proteins (4): NP_001230097, NP_001230098, NP_001230099, NP_612153* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013783	Ig-like_fold	Homologous_superfamily
IPR027834	PTCRA	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF15028

UniProt features (35 total): sequence variant 14, strand 6, splice variant 2, topological domain 2, sequence conflict 2, disulfide bond 2, signal peptide 1, chain 1, transmembrane region 1, turn 1, helix 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3OF6	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ISU1-F1	64.24	0.21

Functional residue map

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

Disulfide bonds (2): 47–107, 135

Glycosylation sites (1): 67

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9013508	NOTCH3 Intracellular Domain Regulates Transcription

MSigDB gene sets: 315 (showing top): REACTOME_SIGNALING_BY_NOTCH, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_T_CELL_APOPTOTIC_PROCESS, SHANK_TAL1_TARGETS_DN, GOBP_REGULATION_OF_THYMOCYTE_APOPTOTIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, MODULE_301, GOBP_NEGATIVE_REGULATION_OF_T_CELL_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, GOBP_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_ALPHA_BETA_T_CELL_ACTIVATION, MODULE_188

GO Biological Process (2): alpha-beta T cell differentiation (GO:0046632), negative regulation of thymocyte apoptotic process (GO:0070244)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by NOTCH3	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
T cell differentiation	1
alpha-beta T cell activation	1
negative regulation of T cell apoptotic process	1
thymocyte apoptotic process	1
regulation of thymocyte apoptotic process	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTCRA	CD3G	P09693	787
PTCRA	CD8A	P01732	684
PTCRA	CD3D	P04234	674
PTCRA	CD4	P01730	668
PTCRA	DTX1	Q86Y01	653
PTCRA	IL7R	P16871	632
PTCRA	RAG1	P15918	604
PTCRA	CD247	P20963	599
PTCRA	RAG2	P55895	576
PTCRA	BCL11B	Q9C0K0	519
PTCRA	NRARP	Q7Z6K4	514
PTCRA	LYL1	P12980	513
PTCRA	NOTCH1	P46531	512
PTCRA	LCK	P06239	511
PTCRA	NOTCH3	Q9UM47	506

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PTCRA	CTH	psi-mi:“MI:0914”(association)	0.350
USP19	PTCRA	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): HDLBP (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), TCEA1 (Affinity Capture-MS), TCEA1 (Affinity Capture-MS), CTH (Affinity Capture-MS), FEN1 (Affinity Capture-MS), FEN1 (Affinity Capture-MS), CTH (Affinity Capture-MS), NOTCH3 (Affinity Capture-Western), PTCRA (Affinity Capture-Western), PTCRA (Affinity Capture-Western), PTCRA (Affinity Capture-Western)

ESM2 similar proteins: A2TGX5, A5PJC7, D7PDD4, O70540, O95866, O95944, P01732, P0C6B2, P0C6B3, P0CAN6, P11911, P11912, P14753, P18627, P22273, P26954, P26955, P32927, P40238, P41688, Q01114, Q02242, Q07303, Q08351, Q14773, Q1ERP8, Q495A1, Q5BK54, Q5NKT8, Q5R8H1, Q61790, Q61826, Q6DKI7, Q6ISU1, Q6MG59, Q6SJQ0, Q6UWB1, Q6UXG3, Q7L513, Q80ZE3

Diamond homologs: P0C6B2, P0C6B3, Q0VCS0, Q6ISU1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PTCRA	“up-regulates activity”	ZAP70	binding
PTCRA	“up-regulates activity”	LCK	binding
TCF12	“up-regulates quantity by expression”	PTCRA	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	41
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3338636	NM_138296.3(PTCRA):c.296_299del (p.Leu99fs)	Pathogenic

SpliceAI

816 predictions. Top by Δscore:

Variant	Effect	Δscore
6:42924219:T:TA	acceptor_gain	1.0000
6:42924271:GGG:G	donor_gain	1.0000
6:42924272:GGG:G	donor_gain	1.0000
6:42923274:G:GT	donor_gain	0.9900
6:42924220:G:A	acceptor_gain	0.9900
6:42924272:GG:G	donor_gain	0.9900
6:42924273:GG:G	donor_gain	0.9900
6:42924274:G:A	donor_loss	0.9900
6:42924275:T:TC	donor_loss	0.9900
6:42916126:AGG:A	donor_loss	0.9800
6:42916127:GGT:G	donor_loss	0.9800
6:42916128:G:A	donor_loss	0.9800
6:42916129:T:G	donor_loss	0.9800
6:42923260:G:GT	donor_gain	0.9700
6:42924223:CAACA:C	acceptor_loss	0.9700
6:42924225:ACAG:A	acceptor_loss	0.9700
6:42924227:A:AT	acceptor_loss	0.9700
6:42924274:G:GG	donor_gain	0.9700
6:42924275:TGAG:T	acceptor_loss	0.9700
6:42924276:GAGTA:G	acceptor_loss	0.9700
6:42924269:CAGGG:C	donor_gain	0.9600
6:42924270:AGGG:A	donor_gain	0.9600
6:42924271:GGGG:G	donor_gain	0.9600
6:42924274:GTGA:G	acceptor_loss	0.9600
6:42924277:AGTAC:A	acceptor_loss	0.9600
6:42916128:G:GG	donor_gain	0.9500
6:42924224:A:AG	acceptor_gain	0.9500
6:42924228:GGAGA:G	acceptor_gain	0.9500
6:42924273:GGTGA:G	acceptor_loss	0.9500
6:42924121:A:G	acceptor_gain	0.9400

AlphaMissense

1751 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:42923156:T:C	F63S	0.994
6:42923156:T:G	F63C	0.993
6:42923155:T:C	F63L	0.989
6:42923157:C:A	F63L	0.989
6:42923157:C:G	F63L	0.989
6:42923107:T:C	C47R	0.987
6:42923109:C:G	C47W	0.985
6:42923188:T:C	F74L	0.985
6:42923190:C:A	F74L	0.985
6:42923190:C:G	F74L	0.985
6:42923287:T:A	C107S	0.984
6:42923288:G:C	C107S	0.984
6:42923108:G:A	C47Y	0.982
6:42923287:T:C	C107R	0.981
6:42923107:T:A	C47S	0.978
6:42923108:G:C	C47S	0.978
6:42923288:G:A	C107Y	0.975
6:42923274:G:C	W102C	0.970
6:42923274:G:T	W102C	0.970
6:42923289:C:G	C107W	0.968
6:42923108:G:T	C47F	0.961
6:42925313:G:C	K159N	0.956
6:42925313:G:T	K159N	0.956
6:42923189:T:G	F74C	0.953
6:42923158:T:C	S64P	0.950
6:42923236:G:C	A90P	0.950
6:42923154:G:C	W62C	0.948
6:42923154:G:T	W62C	0.948
6:42923226:G:C	W86C	0.947
6:42923226:G:T	W86C	0.947

dbSNP variants (sampled 300 via entrez): RS1000414551 (6:42918405 T>C), RS1000475886 (6:42922596 C>T), RS1000529191 (6:42922382 A>C,G), RS1000851346 (6:42916569 A>G), RS1001046764 (6:42915839 A>G), RS1001144077 (6:42919762 G>A,T), RS1001158845 (6:42919473 G>A), RS1001438451 (6:42916133 C>T), RS1002210340 (6:42917333 C>A), RS1002344576 (6:42917077 C>T), RS1002456033 (6:42914636 C>G,T), RS1002484676 (6:42923892 A>G), RS1002862287 (6:42923583 T>A,C), RS1003063661 (6:42919981 C>T), RS1003214698 (6:42918596 C>T)

Disease associations

OMIM: gene MIM:606817 | disease phenotypes: MIM:620931

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 126, susceptibility to	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
immunodeficiency 126, susceptibility to	Strong	AR

Mondo (1): immunodeficiency 126, susceptibility to (MONDO:0975761)

Orphanet (0):

HPO phenotypes

90 total (30 of 90 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000016	Urinary retention
HP:0000246	Sinusitis
HP:0000509	Conjunctivitis
HP:0000729	Autistic behavior
HP:0000821	Hypothyroidism
HP:0000836	Hyperthyroidism
HP:0000952	Jaundice
HP:0000964	Eczematoid dermatitis
HP:0000988	Skin rash
HP:0001097	Keratoconjunctivitis sicca
HP:0001271	Polyneuropathy
HP:0001324	Muscle weakness
HP:0001409	Portal hypertension
HP:0001433	Hepatosplenomegaly
HP:0001510	Growth delay
HP:0001541	Ascites
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001882	Decreased total leukocyte count
HP:0001888	Decreased total lymphocyte count
HP:0001903	Anemia
HP:0001945	Fever
HP:0002028	Chronic diarrhea
HP:0002039	Anorexia
HP:0002040	Esophageal varix
HP:0002110	Bronchiectasis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002449_4	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005680	omega-6 polyunsaturated fatty acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
aflatoxin B2	affects methylation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	decreases methylation	1
Malathion	decreases expression	1
Zinc Sulfate	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.