GLB1L2

Summary

GLB1L2 (galactosidase beta 1 like 2, HGNC:25129) is a protein-coding gene on chromosome 11q25, encoding Beta-galactosidase-1-like protein 2 (Q8IW92). Probably cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans.

Predicted to enable beta-galactosidase activity. Predicted to be involved in galactose catabolic process. Predicted to be located in extracellular region. Predicted to be active in vacuole.

Source: NCBI Gene 89944 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 148 total
• MANE Select transcript: NM_001370461

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25129
Approved symbol	GLB1L2
Name	galactosidase beta 1 like 2
Location	11q25
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000149328
Ensembl biotype	protein_coding
Entrez	89944

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000529077, ENST00000531081, ENST00000533324, ENST00000535456, ENST00000855671, ENST00000855672

RefSeq mRNA: 3 — MANE Select: NM_001370461 NM_001370460, NM_001370461, NM_138342

CCDS: CCDS31724

Canonical transcript exons

ENST00000535456 — 19 exons

Exon	Start	End
ENSE00001278216	134342754	134342951
ENSE00003294624	134344387	134344455
ENSE00003354183	134374972	134376324
ENSE00003396952	134345034	134345129
ENSE00003489829	134374145	134374256
ENSE00003498818	134368644	134368781
ENSE00003503836	134369805	134369885
ENSE00003541323	134367257	134367341
ENSE00003543695	134370293	134370399
ENSE00003602334	134371752	134371830
ENSE00003614869	134374602	134374718
ENSE00003627509	134359060	134359141
ENSE00003629192	134373721	134373808
ENSE00003645599	134371421	134371492
ENSE00003648073	134364328	134364398
ENSE00003651394	134356301	134356393
ENSE00003657371	134347325	134347433
ENSE00003693687	134371008	134371148
ENSE00003897460	134331988	134332147

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 94.29.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9518 / max 81.9476, expressed in 721 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117707	2.2215	671
117708	0.7276	291
117709	0.0027	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	94.29	gold quality
decidua	UBERON:0002450	93.37	gold quality
mucosa of transverse colon	UBERON:0004991	90.84	gold quality
cortical plate	UBERON:0005343	89.56	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.45	gold quality
prostate gland	UBERON:0002367	87.29	gold quality
epithelium of bronchus	UBERON:0002031	86.91	gold quality
bronchus	UBERON:0002185	86.24	gold quality
transverse colon	UBERON:0001157	85.89	gold quality
right lobe of thyroid gland	UBERON:0001119	85.86	gold quality
left lobe of thyroid gland	UBERON:0001120	85.51	gold quality
bronchial epithelial cell	CL:0002328	85.38	gold quality
right frontal lobe	UBERON:0002810	85.06	gold quality
sigmoid colon	UBERON:0001159	84.97	gold quality
body of uterus	UBERON:0009853	84.89	gold quality
thyroid gland	UBERON:0002046	84.80	gold quality
ileal mucosa	UBERON:0000331	84.54	silver quality
myometrium	UBERON:0001296	84.42	gold quality
colon	UBERON:0001155	83.46	gold quality
rectum	UBERON:0001052	83.28	gold quality
nasal cavity epithelium	UBERON:0005384	83.28	gold quality
pituitary gland	UBERON:0000007	83.12	gold quality
large intestine	UBERON:0000059	83.07	gold quality
adenohypophysis	UBERON:0002196	82.90	gold quality
left ovary	UBERON:0002119	82.66	gold quality
body of stomach	UBERON:0001161	82.55	gold quality
adult mammalian kidney	UBERON:0000082	82.19	gold quality
cingulate cortex	UBERON:0003027	80.92	gold quality
anterior cingulate cortex	UBERON:0009835	80.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting GLB1L2, 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-5193	100.00	67.26	1744
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-3944-5P	98.50	67.55	997

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-224e22.2	ENSDARG00000034941
danio_rerio	b3gat1b	ENSDARG00000055279
mus_musculus	Glb1l2	ENSMUSG00000036395
rattus_norvegicus	Glb1l2	ENSRNOG00000007561
drosophila_melanogaster	Gal	FBGN0001089
drosophila_melanogaster	Ect3	FBGN0260746
caenorhabditis_elegans		WBGENE00011832
caenorhabditis_elegans		WBGENE00019225

Paralogs (3): GLB1L (ENSG00000163521), GLB1L3 (ENSG00000166105), GLB1 (ENSG00000170266)

Protein

Protein identifiers

Beta-galactosidase-1-like protein 2 — Q8IW92 (reviewed: Q8IW92)

All UniProt accessions (1): Q8IW92

UniProt curated annotations — full annotation on UniProt →

Function. Probably cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans.

Similarity. Belongs to the glycosyl hydrolase 35 family.

RefSeq proteins (3): NP_001357389, NP_001357390, NP_612351 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001944	Glycoside_Hdrlase_35	Family
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR017853	GH_hydrolase_sf	Homologous_superfamily
IPR019801	Glyco_hydro_35_CS	Conserved_site
IPR026283	B-gal_1-like	Family
IPR031330	Gly_Hdrlase_35_cat	Domain
IPR048912	BetaGal1-like_ABD1	Domain
IPR048913	BetaGal_gal-bd	Domain

Pfam: PF01301, PF21317, PF21467

UniProt features (11 total): binding site 4, sequence conflict 3, active site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IW92-F1	93.95	0.90

Functional residue map

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

Catalytic / active sites (2): 201 (proton donor); 277 (nucleophile)

Ligand- & substrate-binding residues (4): 96; 142; 200; 344

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2022857	Keratan sulfate degradation
R-HSA-2024101	CS/DS degradation
R-HSA-9840310	Glycosphingolipid catabolism

MSigDB gene sets: 87 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, BROWNE_HCMV_INFECTION_6HR_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_GALACTOSE_METABOLIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_CATABOLIC_PROCESS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, REACTOME_SPHINGOLIPID_METABOLISM, DOUGLAS_BMI1_TARGETS_UP, GOBP_MONOSACCHARIDE_METABOLIC_PROCESS, chr11q25

GO Biological Process (2): galactose catabolic process (GO:0019388), carbohydrate metabolic process (GO:0005975)

GO Molecular Function (5): beta-galactosidase activity (GO:0004565), hydrolase activity, hydrolyzing O-glycosyl compounds (GO:0004553), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (2): extracellular region (GO:0005576), vacuole (GO:0005773)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Keratan sulfate/keratin metabolism	1
Chondroitin sulfate/dermatan sulfate metabolism	1
Glycosphingolipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
galactose metabolic process	1
hexose catabolic process	1
primary metabolic process	1
galactosidase activity	1
hydrolase activity, acting on glycosyl bonds	1
binding	1
catalytic activity	1
hydrolase activity	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLB1L2	PATE3	B3GLJ2	595
GLB1L2	PATE2	Q6UY27	560
GLB1L2	PATE1	Q8WXA2	543
GLB1L2	PRR32	B1ATL7	502
GLB1L2	DEFB115	Q30KQ5	481
GLB1L2	CLPSL2	Q6UWE3	447
GLB1L2	PATE4	P0C8F1	423
GLB1L2	ZNF431	Q8TF32	417
GLB1L2	AFAP1L1	Q8TED9	411
GLB1L2	LRRC23	Q53EV4	411
GLB1L2	LENG9	Q96B70	391
GLB1L2	TMEM109	Q9BVC6	381
GLB1L2	RIBC1	Q8N443	379
GLB1L2	RNASE13	Q5GAN3	379
GLB1L2	DNALI1	O14645	377

IntAct

84 interactions, top by confidence:

A	B	Type	Score
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
CYSRT1	GLB1L2	psi-mi:“MI:0915”(physical association)	0.560
GLB1L2	CAMK2A	psi-mi:“MI:0915”(physical association)	0.560
FUT1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
SCN3B	ABCC5	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
PEX19	FAM20B	psi-mi:“MI:0914”(association)	0.530
FUT3	C1QL1	psi-mi:“MI:0914”(association)	0.530
P2RX1	ATE1	psi-mi:“MI:0914”(association)	0.530
GLB1L2	HSPA5	psi-mi:“MI:0914”(association)	0.530
CHST6	CANX	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
TMED6	SMPD2	psi-mi:“MI:0914”(association)	0.530
NCEH1	CLGN	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
ASIC4	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
ATP2B2	GPR89A	psi-mi:“MI:0914”(association)	0.350
MPPE1	ADAM10	psi-mi:“MI:0914”(association)	0.350
NCEH1	C1QL1	psi-mi:“MI:0914”(association)	0.350
PNLDC1	C1QL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (97): GLB1L2 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), SPTB (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS)

ESM2 similar proteins: A2RSQ1, O19015, O22585, P10538, P16278, P23780, P45582, P48980, P49676, Q00662, Q0DGD7, Q0INM3, Q0IZZ8, Q3UPY5, Q58D55, Q5R7P4, Q5XIL5, Q60HF6, Q60V90, Q67VU7, Q6L6S1, Q6UWU2, Q75HQ3, Q7G3T8, Q7XFK2, Q7Y223, Q8GX69, Q8IW92, Q8NCI6, Q8RUV9, Q8VC60, Q8VZR2, Q93324, Q93Z24, Q95LV1, Q966W3, Q9C6W4, Q9FN08, Q9FZ29, Q9GV16

Diamond homologs: A1CE56, A1D199, A1D1Z9, A1DJ58, A1DM65, A2QA64, A2QAN3, A2QL84, A2RSQ1, A6RPN7, A7EBU5, A7EZS5, B0XMP7, B0XNY2, B0XXE7, B0Y752, B2W791, B6GW04, B6H5X9, B6QHA9, B6QLF0, B8N2I5, B8N6V7, B8NKI4, B8QGZ3, I0AIT9, O19015, P16278, P23780, P29853, P48982, Q0CMF3, Q0DGD7, Q2U6P1, Q2UCU3, Q2UMD5, Q3UPY5, Q4WG05, Q4WNE4, Q4WRD3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metal ion SLC transporters	5	48.5×	2e-05
Platelet homeostasis	5	22.5×	2e-04
Ion transport by P-type ATPases	5	16.7×	6e-04
Ion homeostasis	5	16.4×	6e-04
Cardiac conduction	7	12.3×	1e-04
Ion channel transport	6	9.3×	2e-03
Muscle contraction	7	8.7×	6e-04
Transport of small molecules	12	4.9×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	8	64.6×	1e-10
intracellular zinc ion homeostasis	7	38.7×	1e-07
calcium ion transmembrane transport	5	12.1×	5e-03
sodium ion transmembrane transport	5	11.7×	5e-03
calcium ion transport	5	10.4×	7e-03
ERAD pathway	5	10.4×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	109
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

4335 predictions. Top by Δscore:

Variant	Effect	Δscore
11:134342892:G:GT	donor_gain	1.0000
11:134342952:G:GG	donor_gain	1.0000
11:134344453:G:GT	donor_gain	1.0000
11:134344453:GGA:G	donor_gain	1.0000
11:134344454:GAG:G	donor_gain	1.0000
11:134344456:G:GG	donor_gain	1.0000
11:134347317:A:AG	acceptor_gain	1.0000
11:134347318:C:G	acceptor_gain	1.0000
11:134356296:CGCA:C	acceptor_loss	1.0000
11:134356297:GCA:G	acceptor_loss	1.0000
11:134356299:A:AG	acceptor_gain	1.0000
11:134356300:G:GA	acceptor_gain	1.0000
11:134356300:GT:G	acceptor_gain	1.0000
11:134356300:GTAC:G	acceptor_gain	1.0000
11:134356300:GTACA:G	acceptor_gain	1.0000
11:134356390:GAAG:G	donor_gain	1.0000
11:134356391:AAGG:A	donor_loss	1.0000
11:134356392:AGG:A	donor_loss	1.0000
11:134356393:GGTA:G	donor_loss	1.0000
11:134356394:G:C	donor_loss	1.0000
11:134356394:G:GG	donor_gain	1.0000
11:134356395:T:G	donor_loss	1.0000
11:134359137:GGGAG:G	donor_gain	1.0000
11:134359138:GGAGG:G	donor_gain	1.0000
11:134359139:G:GT	donor_gain	1.0000
11:134359139:G:T	donor_gain	1.0000
11:134364326:A:AC	acceptor_loss	1.0000
11:134364326:A:AG	acceptor_gain	1.0000
11:134364327:G:A	acceptor_loss	1.0000
11:134364327:G:GG	acceptor_gain	1.0000

AlphaMissense

4161 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:134356342:T:A	N200K	0.997
11:134356342:T:G	N200K	0.997
11:134347357:G:C	R161T	0.996
11:134347358:G:C	R161S	0.995
11:134347358:G:T	R161S	0.995
11:134356344:A:T	E201V	0.995
11:134368775:A:C	S341R	0.995
11:134368777:C:A	S341R	0.995
11:134368777:C:G	S341R	0.995
11:134347357:G:T	R161M	0.994
11:134356341:A:T	N200I	0.994
11:134344397:T:A	W99R	0.993
11:134344397:T:C	W99R	0.993
11:134345105:A:T	E142V	0.993
11:134371792:G:C	R490P	0.993
11:134342882:G:C	R72P	0.992
11:134356325:G:C	A195P	0.992
11:134356338:A:T	E199V	0.991
11:134356345:A:C	E201D	0.991
11:134356345:A:T	E201D	0.991
11:134345081:G:C	R134P	0.990
11:134367293:G:T	G281W	0.990
11:134368693:C:A	N313K	0.990
11:134368693:C:G	N313K	0.990
11:134342866:T:C	S67P	0.989
11:134345100:C:G	C140W	0.989
11:134367299:T:C	F283L	0.989
11:134367301:T:A	F283L	0.989
11:134367301:T:G	F283L	0.989
11:134371788:G:T	G489W	0.989

dbSNP variants (sampled 300 via entrez): RS1000025628 (11:134375061 G>A), RS1000072890 (11:134334568 C>T), RS1000231227 (11:134330686 A>G), RS1000237621 (11:134330405 T>C), RS1000265098 (11:134355918 G>A), RS1000305278 (11:134367704 C>T), RS1000391985 (11:134360917 G>T), RS1000417007 (11:134340812 A>G), RS1000457020 (11:134362700 G>A,C), RS1000505952 (11:134357049 G>A), RS1000613981 (11:134357371 G>A), RS1000679935 (11:134359037 G>A), RS1000764502 (11:134358128 C>G,T), RS1000784828 (11:134361973 C>T), RS1000789620 (11:134345892 A>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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
Valproic Acid	affects expression, increases expression	5
sodium arsenite	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Copper	affects binding, decreases expression	1
Endosulfan	decreases expression	1
Estradiol	increases expression	1
Progesterone	increases expression	1
Smoke	increases abundance, increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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