GPA33

Summary

GPA33 (glycoprotein A33, HGNC:4445) is a protein-coding gene on chromosome 1q24.1, encoding Cell surface A33 antigen (Q99795). May play a role in cell-cell recognition and signaling.

The glycoprotein encoded by this gene is a cell surface antigen that is expressed in greater than 95% of human colon cancers. The open reading frame encodes a 319-amino acid polypeptide having a putative secretory signal sequence and 3 potential glycosylation sites. The predicted mature protein has a 213-amino acid extracellular region, a single transmembrane domain, and a 62-amino acid intracellular tail. The sequence of the extracellular region contains 2 domains characteristic of the CD2 subgroup of the immunoglobulin (Ig) superfamily.

Source: NCBI Gene 10223 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 61 total
• Druggable target: yes
• MANE Select transcript: NM_005814

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4445
Approved symbol	GPA33
Name	glycoprotein A33
Location	1q24.1
Locus type	gene with protein product
Status	Approved
Aliases	A33
Ensembl gene	ENSG00000143167
Ensembl biotype	protein_coding
OMIM	602171
Entrez	10223

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000367868, ENST00000527955, ENST00000534512, ENST00000632571, ENST00000903063, ENST00000903064, ENST00000903065, ENST00000903066, ENST00000903067, ENST00000903068, ENST00000903069, ENST00000903070, ENST00000903071, ENST00000903072

RefSeq mRNA: 1 — MANE Select: NM_005814 NM_005814

CCDS: CCDS1258

Canonical transcript exons

ENST00000367868 — 7 exons

Exon	Start	End
ENSE00001445813	167090245	167090377
ENSE00003466883	167068922	167069138
ENSE00003509770	167063582	167063737
ENSE00003566010	167073385	167073539
ENSE00003627151	167054976	167055111
ENSE00003658709	167055730	167055849
ENSE00003661478	167052836	167054466

Expression profiles

Bgee: expression breadth ubiquitous, 110 present calls, max score 99.12.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9094 / max 306.4906, expressed in 103 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15758	0.4350	94
15753	0.2731	16
15754	0.1042	11
15757	0.0563	9
15755	0.0321	9
15756	0.0086	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.12	gold quality
mucosa of transverse colon	UBERON:0004991	99.04	gold quality
colonic mucosa	UBERON:0000317	98.86	gold quality
rectum	UBERON:0001052	98.72	gold quality
jejunal mucosa	UBERON:0000399	98.68	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.63	gold quality
duodenum	UBERON:0002114	94.69	gold quality
transverse colon	UBERON:0001157	89.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.05	gold quality
small intestine	UBERON:0002108	88.22	gold quality
vermiform appendix	UBERON:0001154	86.17	gold quality
caecum	UBERON:0001153	83.90	gold quality
intestine	UBERON:0000160	81.37	gold quality
colonic epithelium	UBERON:0000397	79.69	gold quality
large intestine	UBERON:0000059	79.20	gold quality
colon	UBERON:0001155	78.34	gold quality
jejunum	UBERON:0002115	77.08	gold quality
granulocyte	CL:0000094	72.63	gold quality
blood	UBERON:0000178	68.65	gold quality
lymph node	UBERON:0000029	65.85	gold quality
smooth muscle tissue	UBERON:0001135	65.77	gold quality
decidua	UBERON:0002450	64.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.87	gold quality
endothelial cell	CL:0000115	63.54	gold quality
germinal epithelium of ovary	UBERON:0001304	63.32	gold quality
sperm	CL:0000019	63.05	gold quality
apex of heart	UBERON:0002098	62.57	gold quality
male germ cell	CL:0000015	62.15	gold quality
leukocyte	CL:0000738	61.94	gold quality
sigmoid colon	UBERON:0001159	61.88	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	28.80
E-ANND-3	yes	10.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX1, KLF4, PPARA, PPARG

miRNA regulators (miRDB)

57 targeting GPA33, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3978	99.24	68.39	2201

Literature-anchored findings (GeneRIF, showing 10)

• cloning, chromosomal localizations, exon-intron structures and transcription start sites - target gene for the intestine-specific homeobox transcription factor, CDX1. (PMID:12114523)
• Regulation of A33 antigen expression by GKLF. (PMID:12853980)
• This work has demonstrated that the antigen is both highly immobile and extremely persistent-retaining its surface localization for a turnover halflife of greater than 2 days. (PMID:18236042)
• The A33-dependent incorporation of B5 into extracellular enveloped vaccinia virions is mediated through an interaction between their lumenal domains. (PMID:22623777)
• Increased interaction between vaccinia virus proteins A33 and B5 is detrimental to infectious extracellular enveloped virion production. (PMID:22623782)
• Data indicate that EpCAM- and A33-Exos were released from the apical and basolateral surfaces, respectively. (PMID:23230278)
• Data indicate positive staining was observed for both A33 expression and KRN330 binding from patients biopsied on Day 8, 9 or 14 following initial dosing of 3 mg/kg. (PMID:23294608)
• A33 expression is directly correlated to colorectal tumor differentiation. (PMID:27272411)
• A33 shows similar sensitivity to but is more specific than CDX2 as an immunomarker of colorectal carcinoma (PMID:28226180)
• A panel of intestinal differentiation markers (CDX2, GPA33, and LI-cadherin) identifies gastric cancer patients with favourable prognosis. (PMID:32215766)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpa33b	ENSDARG00000040898
mus_musculus	Gpa33	ENSMUSG00000000544
rattus_norvegicus	Gpa33	ENSRNOG00000003740

Paralogs (14): VSIG2 (ENSG00000019102), VSIG1 (ENSG00000101842), VSIR (ENSG00000107738), IGSF11 (ENSG00000144847), ESAM (ENSG00000149564), CXADR (ENSG00000154639), JAM2 (ENSG00000154721), F11R (ENSG00000158769), MXRA8 (ENSG00000162576), JAM3 (ENSG00000166086), CLMP (ENSG00000166250), MUC15 (ENSG00000169550), VSTM2B (ENSG00000187135), VSIG8 (ENSG00000243284)

Protein

Protein identifiers

Cell surface A33 antigen — Q99795 (reviewed: Q99795)

Alternative names: Glycoprotein A33

All UniProt accessions (3): Q99795, A0A0J9YXH7, E9PMB2

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in cell-cell recognition and signaling.

Subcellular location. Membrane.

Tissue specificity. Expressed in normal gastrointestinal epithelium and in 95% of colon cancers.

Post-translational modifications. N-glycosylated, contains approximately 8 kDa of N-linked carbohydrate. Palmitoylated.

RefSeq proteins (1): NP_005805* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR042474	A33	Family

Pfam: PF07686, PF13927

UniProt features (18 total): glycosylation site 3, disulfide bond 3, sequence variant 2, topological domain 2, domain 2, compositionally biased region 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99795-F1	84.47	0.67

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 (3): 43–117, 146–222, 162–211

Glycosylation sites (3): 112, 200, 223

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 128 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, MYOGENIN_Q6, MODULE_45, MODULE_64, MODULE_16, CHANG_IMMORTALIZED_BY_HPV31_DN, MODULE_88, MODULE_113, ELK1_01, MORF_PDPK1, MODULE_18, MODULE_11, MODULE_60, MODULE_38, LEE_RECENT_THYMIC_EMIGRANT

GO Biological Process (0):

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

GO Cellular Component (3): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPA33	HSF4	Q9ULV5	810
GPA33	CYP27A1	Q02318	766
GPA33	EPCAM	P16422	590
GPA33	EGFR	P00533	503
GPA33	FRMD4B	Q9Y2L6	461
GPA33	GSTA3	Q16772	443
GPA33	TM4SF20	Q53R12	441
GPA33	CD24	P25063	415
GPA33	SCAMP2	O15127	413
GPA33	BRD3	Q15059	410
GPA33	PARP4	Q9UKK3	410
GPA33	FOLH1	Q04609	397
GPA33	NADK	O95544	382
GPA33	TNFAIP3	P21580	371
GPA33	FCER2	P06734	370

IntAct

29 interactions, top by confidence:

A	B	Type	Score
UPK2	GPA33	psi-mi:“MI:0915”(physical association)	0.560
NRSN1	GPA33	psi-mi:“MI:0915”(physical association)	0.560
ENTPD3	GPA33	psi-mi:“MI:0915”(physical association)	0.560
EMP3	GPA33	psi-mi:“MI:0915”(physical association)	0.560
MALL	GPA33	psi-mi:“MI:0915”(physical association)	0.560
GPA33	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
NSG1	GPA33	psi-mi:“MI:0915”(physical association)	0.560
POT1	GPA33	psi-mi:“MI:0915”(physical association)	0.510
GPA33	CTDSP2	psi-mi:“MI:0915”(physical association)	0.400
	SDCBP	psi-mi:“MI:0914”(association)	0.350
GPA33	ATE1	psi-mi:“MI:0914”(association)	0.350
	IPO5	psi-mi:“MI:0914”(association)	0.350
	MYO1C	psi-mi:“MI:0914”(association)	0.350
POT1	GPA33	psi-mi:“MI:0915”(physical association)	0.000
UPK2	GPA33	psi-mi:“MI:0915”(physical association)	0.000
NRSN1	GPA33	psi-mi:“MI:0915”(physical association)	0.000
ENTPD3	GPA33	psi-mi:“MI:0915”(physical association)	0.000
EMP3	GPA33	psi-mi:“MI:0915”(physical association)	0.000
NSG1	GPA33	psi-mi:“MI:0915”(physical association)	0.000
MALL	GPA33	psi-mi:“MI:0915”(physical association)	0.000
SMCO4	GPA33	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): GPA33 (Affinity Capture-MS), GPA33 (Affinity Capture-RNA), GPA33 (Two-hybrid), GPA33 (Two-hybrid), MALL (Two-hybrid), NRSN1 (Two-hybrid), SMCO4 (Two-hybrid), ENTPD3 (Two-hybrid), NSG1 (Two-hybrid), CTDSP2 (Affinity Capture-MS), NSF (Affinity Capture-MS), KLHL22 (Affinity Capture-MS), ATE1 (Affinity Capture-MS), DNAJC11 (Affinity Capture-MS), GPX4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IGV4, A0A8M2B818, A0JM41, A2VD98, B0CLX4, B6ZK77, D3YX43, F1LW30, O00241, O18906, O54901, O88775, O95256, P00545, P04218, P0C673, P10522, P13369, P17948, P21995, P27931, P35916, P35917, P35969, P37301, P42071, P42703, P53767, Q08DK1, Q15762, Q58EG3, Q5DX21, Q5FWR8, Q5R412, Q5U2P2, Q5VJ70, Q6GMZ9, Q6PCB8, Q6X936, Q7TSN7

Diamond homologs: O08859, O14594, P03994, P07354, P07897, P07898, P10859, P10915, P13608, P13611, P16112, P41725, P55066, P55067, P55068, P55252, P81282, P98065, P98066, Q28062, Q28343, Q28381, Q28670, Q28858, Q29011, Q5IS41, Q61282, Q61361, Q62059, Q80WM4, Q80WM5, Q86UW8, Q8CFM6, Q8R4U0, Q8R4Y4, Q8WWQ8, Q90953, Q96GW7, Q96S86, Q99795

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2870 predictions. Top by Δscore:

Variant	Effect	Δscore
1:167054464:TTCCT:T	acceptor_loss	1.0000
1:167054465:TC:T	acceptor_gain	1.0000
1:167054465:TCCTG:T	acceptor_loss	1.0000
1:167054466:CC:C	acceptor_gain	1.0000
1:167054467:C:CC	acceptor_gain	1.0000
1:167054476:A:T	acceptor_gain	1.0000
1:167054478:C:CT	acceptor_gain	1.0000
1:167054479:A:T	acceptor_gain	1.0000
1:167054974:A:AC	donor_gain	1.0000
1:167054974:ACGGC:A	donor_gain	1.0000
1:167054975:C:CC	donor_gain	1.0000
1:167054975:CG:C	donor_gain	1.0000
1:167054975:CGG:C	donor_gain	1.0000
1:167054975:CGGCC:C	donor_gain	1.0000
1:167054985:T:TA	donor_gain	1.0000
1:167054988:T:TA	donor_gain	1.0000
1:167055108:GAGG:G	acceptor_gain	1.0000
1:167055110:GG:G	acceptor_gain	1.0000
1:167055112:C:CC	acceptor_gain	1.0000
1:167055728:A:AC	donor_gain	1.0000
1:167055729:C:CC	donor_gain	1.0000
1:167055729:CGAG:C	donor_gain	1.0000
1:167055848:GGC:G	acceptor_loss	1.0000
1:167055850:C:CA	acceptor_loss	1.0000
1:167055850:C:CC	acceptor_gain	1.0000
1:167055851:T:C	acceptor_loss	1.0000
1:167063579:TA:T	donor_loss	1.0000
1:167063581:CC:C	donor_loss	1.0000
1:167063581:CCTGG:C	donor_gain	1.0000
1:167063733:TGGCA:T	acceptor_gain	1.0000

AlphaMissense

2077 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:167063628:C:A	W175C	0.998
1:167063628:C:G	W175C	0.998
1:167073409:C:A	W58C	0.996
1:167073409:C:G	W58C	0.996
1:167055789:C:G	C211S	0.995
1:167055790:A:T	C211S	0.995
1:167068987:C:G	C117S	0.994
1:167068988:A:T	C117S	0.994
1:167063630:A:G	W175R	0.992
1:167063630:A:T	W175R	0.992
1:167063668:C:G	C162S	0.992
1:167063669:A:T	C162S	0.992
1:167055788:A:C	C211W	0.991
1:167055789:C:T	C211Y	0.990
1:167068988:A:G	C117R	0.990
1:167073411:A:G	W58R	0.990
1:167073411:A:T	W58R	0.990
1:167055790:A:G	C211R	0.989
1:167068986:A:C	C117W	0.989
1:167068994:A:C	Y115D	0.988
1:167063669:A:G	C162R	0.987
1:167063668:C:T	C162Y	0.986
1:167063667:G:C	C162W	0.984
1:167069005:T:A	D111V	0.983
1:167063674:A:G	L160P	0.982
1:167063716:C:G	C146S	0.981
1:167063717:A:G	C146R	0.981
1:167063717:A:T	C146S	0.981
1:167073455:C:G	C43S	0.981
1:167073456:A:T	C43S	0.981

dbSNP variants (sampled 300 via entrez): RS1000008862 (1:167090573 C>T), RS1000076985 (1:167079455 G>A,T), RS1000106831 (1:167059168 A>C), RS1000169540 (1:167058168 C>T), RS1000228067 (1:167090944 C>T), RS1000267778 (1:167052899 C>T), RS1000277193 (1:167063859 T>G), RS1000336251 (1:167090307 C>T), RS1000370211 (1:167080166 A>G), RS1000431425 (1:167085638 C>T), RS1000486260 (1:167079856 A>T), RS1000551570 (1:167086428 C>A,T), RS1000607244 (1:167056170 G>A), RS1000616389 (1:167085362 G>A,C), RS1000703905 (1:167081231 G>T)

Disease associations

OMIM: gene MIM:602171 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009249_1	Eosinophilic granulomatosis with polyangiitis (ANCA negative)	7.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712927 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	2
Cadmium Chloride	increases expression	2
GSK-J4	decreases expression	1
chloroacetaldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid	decreases expression	1
Cidofovir	increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

3 cell lines: 1 spontaneously immortalized cell line, 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E6QL	Genomeditech CHO-K1 H_GPA33	Spontaneously immortalized cell line	Female
CVCL_E6T2	Genomeditech CT26 H_GPA33	Cancer cell line	Female
CVCL_E6TZ	Genomeditech HEK-293 H_GPA33	Transformed cell line	Female

Clinical trials (associated diseases)

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