GAPT

Summary

GAPT (GRB2 binding adaptor protein, transmembrane, HGNC:26588) is a protein-coding gene on chromosome 5q11.2, encoding Protein GAPT (Q8N292). Negatively regulates B-cell proliferation following stimulation through the B-cell receptor.

Predicted to be involved in B cell homeostasis and B cell proliferation involved in immune response. Located in Golgi apparatus and plasma membrane.

Source: NCBI Gene 202309 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_001304431

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26588
Approved symbol	GAPT
Name	GRB2 binding adaptor protein, transmembrane
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ33641
Ensembl gene	ENSG00000175857
Ensembl biotype	protein_coding
OMIM	620440
Entrez	202309

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000318469, ENST00000396776, ENST00000502276, ENST00000511178, ENST00000511930, ENST00000513924, ENST00000515443

RefSeq mRNA: 4 — MANE Select: NM_001304431 NM_001304428, NM_001304429, NM_001304431, NM_152687

CCDS: CCDS3975

Canonical transcript exons

ENST00000502276 — 3 exons

Exon	Start	End
ENSE00001526214	58494247	58497090
ENSE00002058570	58491435	58491541
ENSE00002084074	58493711	58493838

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 97.26.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1342 / max 246.0550, expressed in 280 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56553	3.6144	259
56552	1.5198	179

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.26	gold quality
leukocyte	CL:0000738	97.19	gold quality
granulocyte	CL:0000094	94.27	gold quality
vermiform appendix	UBERON:0001154	94.19	gold quality
blood	UBERON:0000178	90.07	gold quality
lymph node	UBERON:0000029	85.72	gold quality
trabecular bone tissue	UBERON:0002483	85.39	gold quality
bone marrow	UBERON:0002371	84.55	gold quality
spleen	UBERON:0002106	84.36	gold quality
caecum	UBERON:0001153	82.73	gold quality
bone marrow cell	CL:0002092	82.36	gold quality
gall bladder	UBERON:0002110	79.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.68	gold quality
smooth muscle tissue	UBERON:0001135	76.85	gold quality
rectum	UBERON:0001052	73.85	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.28	gold quality
tonsil	UBERON:0002372	68.55	gold quality
small intestine	UBERON:0002108	67.92	gold quality
right lung	UBERON:0002167	67.13	gold quality
right coronary artery	UBERON:0001625	67.08	gold quality
mucosa of transverse colon	UBERON:0004991	66.90	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	66.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.49	silver quality
colonic epithelium	UBERON:0000397	66.45	gold quality
palpebral conjunctiva	UBERON:0001812	66.05	gold quality
epithelium of nasopharynx	UBERON:0001951	65.10	gold quality
upper lobe of left lung	UBERON:0008952	64.96	gold quality
upper lobe of lung	UBERON:0008948	64.52	gold quality
spinal cord	UBERON:0002240	64.28	gold quality
descending thoracic aorta	UBERON:0002345	62.64	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	14.20
E-MTAB-8498	yes	12.59
E-CURD-112	yes	11.43
E-ANND-3	yes	7.64
E-HCAD-10	yes	7.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

92 targeting GAPT, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-545-5P	99.66	70.18	2308

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gapt	ENSMUSG00000046006
rattus_norvegicus	Gapt	ENSRNOG00000026989

Protein

Protein identifiers

Protein GAPT — Q8N292 (reviewed: Q8N292)

Alternative names: GRB2-binding adapter protein, transmembrane, Growth factor receptor-bound protein 2-binding adapter protein, transmembrane

All UniProt accessions (3): D6RA63, D6RBK7, Q8N292

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates B-cell proliferation following stimulation through the B-cell receptor. May play an important role in maintenance of marginal zone (MZ) B-cells.

Subunit / interactions. Interacts with GRB2.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in spleen and PBL, detected at lower levels in thymus, and undetectable in all other tissues tested. Also expressed in various B-cell lines, monocytic cell line THP-1 and NK-like cell line YT, but not in T-cell line Jurkat or HeLa cells.

Similarity. Belongs to the GAPT family.

RefSeq proteins (4): NP_001291357, NP_001291358, NP_001291360, NP_689900 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021082	Protein_GAPT	Family

Pfam: PF11770

UniProt features (7 total): mutagenesis site 3, chain 1, transmembrane region 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N292-F1	62.94	0.07

Functional residue map

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

Mutagenesis-validated functional residues (3):

Position	Phenotype
139	abolishes interaction with grb2.
141	abolishes interaction with grb2.
145	abolishes interaction with grb2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 91 (showing top): GOBP_B_CELL_HOMEOSTASIS, GOBP_B_CELL_ACTIVATION, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOBP_B_CELL_PROLIFERATION, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_LEUKOCYTE_PROLIFERATION, RYTTCCTG_ETS2_B, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_IMMUNE_EFFECTOR_PROCESS, DELASERNA_MYOD_TARGETS_DN, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_UP, GOBP_LYMPHOCYTE_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_LEUKOCYTE_HOMEOSTASIS, TGGAAA_NFAT_Q4_01

GO Biological Process (3): B cell homeostasis (GO:0001782), B cell proliferation involved in immune response (GO:0002322), B cell activation (GO:0042113)

GO Molecular Function (0):

GO Cellular Component (3): Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lymphocyte homeostasis	1
B cell activation involved in immune response	1
immune response	1
B cell proliferation	1
lymphocyte activation	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GAPT	GRB2	P29354	694
GAPT	JAML	Q86YT9	423
GAPT	LAT2	Q9GZY6	402
GAPT	HSBP1L1	C9JCN9	398
GAPT	HSBP1	O75506	398
GAPT	ZMYND15	Q9H091	396
GAPT	BAMBI	Q13145	395
GAPT	OTUD6A	Q7L8S5	391
GAPT	ITGB7	P26010	389
GAPT	OTOR	Q9NRC9	387
GAPT	GARNL3	Q5VVW2	386
GAPT	CD79B	P40259	386
GAPT	CHRNA10	Q9GZZ6	378
GAPT	STOML2	Q9UJZ1	371
GAPT	CPA2	P48052	368

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A6H7B4, B1AXH1, F1RDM5, M3WHG5, O43561, O54957, O70601, O88834, P15391, P16382, P24394, P25917, P25918, Q08DN6, Q13651, Q2TBN9, Q3SYS8, Q3U1F9, Q3UU41, Q58CT8, Q5FVQ5, Q5HYW2, Q5JTC6, Q5M831, Q5S7W5, Q63257, Q6DJE5, Q6P1D7, Q6RFH4, Q6T4R5, Q6WG24, Q7M4L6, Q7TS75, Q863Z5, Q8BHB3, Q8C5R2, Q8CB93, Q8CGK5, Q8IWV1, Q8IY92

Diamond homologs: Q8CB93, Q8N292

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

540 predictions. Top by Δscore:

Variant	Effect	Δscore
5:58491539:GAG:G	donor_gain	0.9900
5:58491542:G:GG	donor_gain	0.9900
5:58491541:GGTA:G	donor_loss	0.9800
5:58491885:TCA:T	donor_gain	0.9800
5:58493835:ACAG:A	donor_gain	0.9800
5:58491546:G:GG	donor_gain	0.9700
5:58491540:AG:A	donor_gain	0.9600
5:58491541:GG:G	donor_gain	0.9600
5:58491545:A:AG	donor_gain	0.9600
5:58493833:TGAC:T	donor_gain	0.9600
5:58491537:TTGAG:T	donor_gain	0.9300
5:58491538:TGAG:T	donor_gain	0.9200
5:58491539:GAGG:G	donor_gain	0.9200
5:58491540:AGGT:A	donor_gain	0.9100
5:58491542:GT:G	donor_gain	0.9100
5:58493808:GA:G	donor_gain	0.9000
5:58493834:GACA:G	donor_gain	0.9000
5:58491543:T:G	donor_gain	0.8800
5:58492061:A:G	donor_gain	0.8600
5:58491539:GAGGT:G	donor_gain	0.8400
5:58491540:AGGTA:A	donor_gain	0.8400
5:58493706:TTTAG:T	acceptor_loss	0.8400
5:58493707:TTAG:T	acceptor_loss	0.8400
5:58493708:TA:T	acceptor_loss	0.8400
5:58493710:G:GA	acceptor_loss	0.8400
5:58494245:A:AG	acceptor_gain	0.8400
5:58494246:G:GG	acceptor_gain	0.8400
5:58491541:GGT:G	donor_gain	0.8300
5:58494185:G:GC	acceptor_gain	0.8200
5:58493709:A:AG	acceptor_gain	0.8100

AlphaMissense

423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:58494609:T:C	C25R	0.928
5:58494612:G:A	G26R	0.897
5:58494612:G:C	G26R	0.897
5:58494619:G:A	G28E	0.894
5:58494613:G:A	G26E	0.869
5:58494618:G:A	G28R	0.864
5:58494618:G:C	G28R	0.864
5:58494579:G:A	G15R	0.851
5:58494579:G:C	G15R	0.851
5:58494621:T:C	C29R	0.824
5:58494672:T:C	F46L	0.791
5:58494674:T:A	F46L	0.791
5:58494674:T:G	F46L	0.791
5:58494607:T:A	V24D	0.772
5:58494627:T:A	W31R	0.772
5:58494627:T:C	W31R	0.772
5:58494598:T:G	L21R	0.771
5:58494657:T:C	F41L	0.764
5:58494659:T:A	F41L	0.764
5:58494659:T:G	F41L	0.764
5:58494589:T:G	L18R	0.763
5:58494580:G:A	G15E	0.751
5:58494589:T:A	L18H	0.727
5:58494592:T:G	L19R	0.721
5:58494598:T:A	L21H	0.720
5:58494604:T:A	V23E	0.703
5:58494589:T:C	L18P	0.674
5:58494667:C:A	P44Q	0.673
5:58494625:T:A	V30D	0.668
5:58494616:T:A	I27N	0.653

dbSNP variants (sampled 300 via entrez): RS1000131058 (5:58492945 A>T), RS1000216421 (5:58492670 A>T), RS1000794616 (5:58492128 T>C), RS1000825412 (5:58492351 A>G), RS1001439548 (5:58492336 C>T), RS1001795015 (5:58493283 G>C), RS1002129114 (5:58489664 T>C), RS1002520959 (5:58496010 C>A,T), RS1002693984 (5:58490516 T>C,G), RS1002963673 (5:58496220 T>G), RS1003018063 (5:58491350 C>A), RS1003111592 (5:58491211 A>G), RS1003718499 (5:58496333 A>G,T), RS1005102318 (5:58489439 C>G,T), RS10051454 (5:58492208 G>A,C)

Disease associations

OMIM: gene MIM:620440 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002936_15	Cadmium levels	9.000000e-06
GCST009391_459	Metabolite levels	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010522	phosphoenolpyruvic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
gardiquimod	decreases reaction, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Carbamazepine	affects expression	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	decreases expression	1
Daunorubicin	affects response to substance	1
Endosulfan	decreases expression	1
Fenfluramine	increases expression	1
Hydrogen Peroxide	increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Nickel	decreases expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	increases methylation	1
Tretinoin	increases expression	1
Aflatoxin B1	increases methylation	1
Protein Kinase Inhibitors	decreases expression, decreases reaction	1

Clinical trials (associated diseases)

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