BAIAP2L2

Summary

BAIAP2L2 (BAR/IMD domain containing adaptor protein 2 like 2, HGNC:26203) is a protein-coding gene on chromosome 22q13.1, encoding BAR/IMD domain-containing adapter protein 2-like 2 (Q6UXY1). Phosphoinositides-binding protein that induces the formation of planar or gently curved membrane structures.

The protein encoded by this gene binds phosphoinositides and promotes the formation of planar or curved membrane structures. The encoded protein is found in RAB13-positive vesicles and at intercellular contacts with the plasma membrane.

Source: NCBI Gene 80115 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 133 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_025045

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26203
Approved symbol	BAIAP2L2
Name	BAR/IMD domain containing adaptor protein 2 like 2
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22582, pinkbar
Ensembl gene	ENSG00000128298
Ensembl biotype	protein_coding
OMIM	617536
Entrez	80115

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000332536, ENST00000381669, ENST00000428572, ENST00000679603, ENST00000680818, ENST00000681084, ENST00000681104, ENST00000871591, ENST00000871592, ENST00000871593, ENST00000947326

RefSeq mRNA: 1 — MANE Select: NM_025045 NM_025045

CCDS: CCDS43018

Canonical transcript exons

ENST00000381669 — 14 exons

Exon	Start	End
ENSE00001109308	38085686	38085732
ENSE00001109310	38087124	38087264
ENSE00001109313	38089096	38089231
ENSE00001289653	38088748	38088964
ENSE00001489401	38086242	38086449
ENSE00001600882	38108255	38108341
ENSE00001706871	38098411	38098482
ENSE00001725358	38084900	38085375
ENSE00001778124	38107852	38107913
ENSE00001778956	38089522	38089674
ENSE00001780552	38098063	38098179
ENSE00001787555	38109133	38109208
ENSE00001793001	38097032	38097178
ENSE00001851731	38110475	38110684

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 96.63.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7487 / max 247.9635, expressed in 668 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194113	2.3848	470
194115	0.9180	70
194114	0.2643	122
194116	0.1817	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	96.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.08	gold quality
lower esophagus mucosa	UBERON:0035834	90.27	gold quality
small intestine	UBERON:0002108	89.74	gold quality
duodenum	UBERON:0002114	89.67	gold quality
transverse colon	UBERON:0001157	89.38	gold quality
ileal mucosa	UBERON:0000331	88.47	gold quality
gall bladder	UBERON:0002110	86.02	gold quality
cortex of kidney	UBERON:0001225	84.17	gold quality
buccal mucosa cell	CL:0002336	83.92	gold quality
rectum	UBERON:0001052	83.37	gold quality
adult mammalian kidney	UBERON:0000082	82.83	gold quality
pancreatic ductal cell	CL:0002079	81.80	silver quality
intestine	UBERON:0000160	81.50	gold quality
right frontal lobe	UBERON:0002810	81.46	gold quality
jejunal mucosa	UBERON:0000399	81.30	gold quality
metanephros cortex	UBERON:0010533	81.17	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.62	gold quality
cerebellar vermis	UBERON:0004720	80.19	silver quality
right uterine tube	UBERON:0001302	79.85	gold quality
anterior cingulate cortex	UBERON:0009835	79.76	gold quality
colon	UBERON:0001155	79.36	gold quality
large intestine	UBERON:0000059	79.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.00	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	78.83	gold quality
prefrontal cortex	UBERON:0000451	78.43	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.25	gold quality
kidney	UBERON:0002113	78.18	gold quality
kidney epithelium	UBERON:0004819	77.81	gold quality
frontal cortex	UBERON:0001870	77.59	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting BAIAP2L2, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-3972	97.19	66.46	808
HSA-MIR-4485-5P	95.91	59.69	198
HSA-MIR-6805-5P	95.79	64.86	670
HSA-MIR-4278	95.28	65.49	351

Literature-anchored findings (GeneRIF, showing 5)

• these findings revealed BAIAP2L2 as a novel biomarker and potential therapeutic target for lung cancer (PMID:30483805)
• BAIAP2L2 promotes the progression of gastric cancer via AKT/mTOR and Wnt3a/beta-catenin signaling pathways. (PMID:32570120)
• BAIAP2L2 facilitates the malignancy of prostate cancer (PCa) via VEGF and apoptosis signaling pathways. (PMID:33646530)
• HNF1beta-associated cyst development and electrolyte disturbances are not explained by BAIAP2L2 expression. (PMID:36520027)
• BAIAP2L2 is a novel prognostic biomarker related to migration and invasion of HCC and associated with cuprotosis. (PMID:37248248)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	baiap2l2a	ENSDARG00000016483
danio_rerio	baiap2l2b	ENSDARG00000060933
mus_musculus	Baiap2l2	ENSMUSG00000018126
rattus_norvegicus	Baiap2l2	ENSRNOG00000012215
drosophila_melanogaster	IRSp53	FBGN0052082

Paralogs (2): BAIAP2L1 (ENSG00000006453), BAIAP2 (ENSG00000175866)

Protein

Protein identifiers

BAR/IMD domain-containing adapter protein 2-like 2 — Q6UXY1 (reviewed: Q6UXY1)

Alternative names: Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 2, Planar intestinal- and kidney-specific BAR domain protein

All UniProt accessions (5): Q6UXY1, A0A7P0T9X8, A0A7P0Z4P0, A0A804CBC2, B0QYF0

UniProt curated annotations — full annotation on UniProt →

Function. Phosphoinositides-binding protein that induces the formation of planar or gently curved membrane structures. Binds to phosphoinositides, including to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) headgroups. There seems to be no clear preference for a specific phosphoinositide.

Subcellular location. Cell membrane. Cell junction. Cytoplasmic vesicle membrane.

Tissue specificity. Expressed in the epithelial layer of the intestine (at protein level).

Domain organisation. The IMD domain consisting of an antiparallel dimer of three-helix bundles, featuring on one side a positively charged. The N-terminal alpha-helix inserts into the lipid bilayer. Also forms homodimers and homooligomers. The residue Trp-141 is essential for oligomer formation.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UXY1-1	1	yes
Q6UXY1-2	2

RefSeq proteins (1): NP_079321* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR013606	I-BAR_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR027681	IRSp53/IRTKS/Pinkbar	Family
IPR030126	Baiap2l2_I-BAR_dom	Domain
IPR035593	Pinkbar_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily

Pfam: PF08397, PF14604

UniProt features (17 total): modified residue 5, compositionally biased region 4, domain 2, sequence conflict 2, region of interest 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXY1-F1	71.34	0.50

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): 272, 302, 478, 481, 231

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9035034	RHOF GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 72 (showing top): GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, NKX25_02, GOBP_PLASMA_MEMBRANE_ORGANIZATION, TGACCTY_ERR1_Q2, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, PATIL_LIVER_CANCER, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY

GO Biological Process (5): plasma membrane organization (GO:0007009), positive regulation of actin filament polymerization (GO:0030838), actin filament bundle assembly (GO:0051017), actin crosslink formation (GO:0051764), membrane organization (GO:0061024)

GO Molecular Function (3): phospholipid binding (GO:0005543), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (10): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), vesicle membrane (GO:0012506), cytoplasmic vesicle membrane (GO:0030659), cell-cell contact zone (GO:0044291), clathrin complex (GO:0071439), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
cytoplasm	2
endomembrane system organization	1
membrane organization	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
cellular component assembly	1
actin filament bundle organization	1
actin filament organization	1
cellular component organization	1
lipid binding	1
nuclear lumen	1
membrane	1
cell periphery	1
organelle membrane	1
vesicle	1
vesicle membrane	1
cytoplasmic vesicle	1
cell-cell junction	1
clathrin coat	1
membrane protein complex	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

818 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BAIAP2L2	WASF2	Q9Y6W5	604
BAIAP2L2	MTSS2	Q765P7	583
BAIAP2L2	AMPH	P49418	535
BAIAP2L2	TMEM272	A0A1B0GTI8	520
BAIAP2L2	BIN1	O00499	479
BAIAP2L2	EPS8	Q12929	460
BAIAP2L2	MTSS1	O43312	446
BAIAP2L2	FCHSD1	Q86WN1	446
BAIAP2L2	TMEM184B	Q9Y519	418
BAIAP2L2	WDPCP	O95876	417
BAIAP2L2	FCHO1	O14526	395
BAIAP2L2	CLRN2	A0PK11	390
BAIAP2L2	RSPO4	Q2I0M5	381
BAIAP2L2	FCHO2	Q0JRZ9	378
BAIAP2L2	EPS8L2	Q9H6S3	378

IntAct

0 interactions, top by confidence:

BioGRID (7): BAIAP2L2 (Two-hybrid), BAIAP2L2 (Two-hybrid), BAIAP2L2 (Two-hybrid), GLYCTK (Two-hybrid), FAM9B (Two-hybrid), GRXCR1 (Two-hybrid), BAIAP2L2 (Affinity Capture-MS)

ESM2 similar proteins: A1Z7A6, A9C3W3, E1BFE9, E7FBF7, F6SEU4, O15085, O35711, O43150, O97902, P62484, P70302, P83093, P84903, Q13586, Q1AAU6, Q1LWE6, Q21653, Q3UHC7, Q58CP9, Q5FWS6, Q5PRF9, Q5RB40, Q5RC07, Q5U464, Q5VWQ8, Q5W7F2, Q674X7, Q69ZS8, Q6DE55, Q6P730, Q6UXY1, Q80Y61, Q8BYZ1, Q8CBY1, Q8ND30, Q8R4H2, Q8TDY4, Q91ZR2, Q95LV5, Q96PV0

Diamond homologs: E1BFE9, Q1LWE6, Q6UXY1, Q80Y61, Q14847, Q5R5W0, Q99MZ8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	114
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3248115	NC_000022.10:g.(?38369502)(38565433_?)del	Pathogenic
4056471	Single allele	Pathogenic
395465	GRCh37/hg19 22q13.1(chr22:38322968-38965458)	Likely pathogenic

SpliceAI

2026 predictions. Top by Δscore:

Variant	Effect	Δscore
22:38085373:CCC:C	acceptor_gain	1.0000
22:38085374:CC:C	acceptor_gain	1.0000
22:38085374:CCC:C	acceptor_gain	1.0000
22:38085375:CC:C	acceptor_gain	1.0000
22:38085376:C:CA	acceptor_loss	1.0000
22:38085376:C:CC	acceptor_gain	1.0000
22:38086237:CTCA:C	donor_loss	1.0000
22:38086238:TCAC:T	donor_loss	1.0000
22:38086239:CACCT:C	donor_loss	1.0000
22:38086240:A:AC	donor_gain	1.0000
22:38086241:C:CC	donor_gain	1.0000
22:38086447:GACC:G	acceptor_loss	1.0000
22:38086450:C:CA	acceptor_loss	1.0000
22:38086450:C:CC	acceptor_gain	1.0000
22:38086451:T:C	acceptor_loss	1.0000
22:38086457:C:CT	acceptor_gain	1.0000
22:38086457:C:T	acceptor_gain	1.0000
22:38086458:A:T	acceptor_gain	1.0000
22:38087119:GGTAC:G	donor_loss	1.0000
22:38087120:GTAC:G	donor_loss	1.0000
22:38087121:TACC:T	donor_loss	1.0000
22:38087123:C:CT	donor_loss	1.0000
22:38087260:CGCTC:C	acceptor_gain	1.0000
22:38087262:CTC:C	acceptor_gain	1.0000
22:38087263:TC:T	acceptor_gain	1.0000
22:38087264:CC:C	acceptor_gain	1.0000
22:38087265:C:CC	acceptor_gain	1.0000
22:38087266:T:C	acceptor_loss	1.0000
22:38088746:A:AC	donor_gain	1.0000
22:38088747:C:CC	donor_gain	1.0000

AlphaMissense

3444 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:38087253:A:G	F377S	0.998
22:38088829:A:G	F346S	0.998
22:38088769:C:T	G366D	0.997
22:38087252:G:C	F377L	0.996
22:38087252:G:T	F377L	0.996
22:38087254:A:G	F377L	0.996
22:38088779:A:G	W363R	0.996
22:38088779:A:T	W363R	0.996
22:38085360:A:C	F510L	0.995
22:38085360:A:T	F510L	0.995
22:38085362:A:G	F510L	0.995
22:38088775:A:G	L364P	0.995
22:38088777:C:A	W363C	0.995
22:38088777:C:G	W363C	0.995
22:38087253:A:C	F377C	0.994
22:38109171:A:G	L30P	0.994
22:38087257:A:G	W376R	0.993
22:38087257:A:T	W376R	0.993
22:38088874:G:T	A331D	0.992
22:38097096:C:G	R183P	0.992
22:38085361:A:C	F510C	0.991
22:38087259:C:T	G375D	0.991
22:38089641:A:G	W216R	0.991
22:38089641:A:T	W216R	0.991
22:38097086:G:C	F186L	0.991
22:38097086:G:T	F186L	0.991
22:38097088:A:G	F186L	0.991
22:38097099:C:G	R182P	0.991
22:38085352:A:T	V513D	0.990
22:38088828:G:C	F346L	0.990

dbSNP variants (sampled 300 via entrez): RS1000043385 (22:38101372 A>T), RS1000117251 (22:38085582 C>T), RS1000140578 (22:38112635 G>A,C,T), RS1000149786 (22:38094957 C>G,T), RS1000187359 (22:38108809 G>A), RS1000231943 (22:38096944 A>C), RS1000248348 (22:38106224 A>G), RS1000291827 (22:38103863 A>C), RS1000360001 (22:38110842 G>GC), RS1000445899 (22:38096599 G>A), RS1000510470 (22:38085721 G>A), RS1000518883 (22:38096691 T>C), RS1000623082 (22:38108563 G>A), RS1000949035 (22:38092357 A>C,G), RS1000975131 (22:38102476 G>C)

Disease associations

OMIM: gene MIM:617536 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): PLA2G6-associated neurodegeneration (MONDO:0017998)

Orphanet (1): PLA2G6-associated neurodegeneration (Orphanet:329303)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010304_37	Cutaneous malignant melanoma	9.000000e-23
GCST010703_11	Brain morphology (MOSTest)	9.000000e-10
GCST012442_11	Age-related hearing impairment	2.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	3
bisphenol A	decreases expression, affects expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
methyleugenol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Caffeine	affects phosphorylation	1
Calcitriol	increases expression	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Endosulfan	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation, decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	affects methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05522374	Not specified	RECRUITING	TIRCON International NBIA Registry