GLIPR1L1

Summary

GLIPR1L1 (GLIPR1 like 1, HGNC:28392) is a protein-coding gene on chromosome 12q21.2, encoding GLIPR1-like protein 1 (Q6UWM5). Required for optimal fertilization at the stage of sperm-oocyte fusion, plays a role in optimizing acrosome function, the translocation of IZUMO1 during the acrosome reaction and the fertilization process.

Predicted to enable molecular adaptor activity. Predicted to be involved in fusion of sperm to egg plasma membrane involved in single fertilization and protein localization involved in acrosome reaction. Predicted to act upstream of or within binding activity of sperm to zona pellucida. Predicted to be located in acrosomal vesicle and sperm head-tail coupling apparatus. Predicted to be part of protein complex involved in cell-cell adhesion. Predicted to be active in extracellular space and outer acrosomal membrane.

Source: NCBI Gene 256710 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001304964

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28392
Approved symbol	GLIPR1L1
Name	GLIPR1 like 1
Location	12q21.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC26856
Ensembl gene	ENSG00000173401
Ensembl biotype	protein_coding
OMIM	610395
Entrez	256710

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000312442, ENST00000378695, ENST00000547144, ENST00000548623

RefSeq mRNA: 2 — MANE Select: NM_001304964 NM_001304964, NM_152779

CCDS: CCDS76578, CCDS9009

Canonical transcript exons

ENST00000378695 — 6 exons

Exon	Start	End
ENSE00001194240	75363102	75363190
ENSE00001194242	75347622	75347722
ENSE00001194244	75343693	75343938
ENSE00002311812	75334670	75334902
ENSE00002351965	75370085	75370560
ENSE00003508767	75369960	75369986

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 94.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0415 / max 128.6181, expressed in 101 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126899	0.9699	95
126898	0.0716	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	94.82	gold quality
left testis	UBERON:0004533	88.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.27	gold quality
testis	UBERON:0000473	85.26	gold quality
right testis	UBERON:0004534	85.21	gold quality
adult organism	UBERON:0007023	84.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.99	gold quality
calcaneal tendon	UBERON:0003701	79.31	gold quality
pancreatic ductal cell	CL:0002079	70.27	silver quality
apex of heart	UBERON:0002098	68.85	gold quality
adrenal tissue	UBERON:0018303	67.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	67.47	gold quality
cerebellar hemisphere	UBERON:0002245	67.37	gold quality
mucosa of stomach	UBERON:0001199	67.28	gold quality
tibialis anterior	UBERON:0001385	67.07	silver quality
cerebellar cortex	UBERON:0002129	66.94	gold quality
corpus callosum	UBERON:0002336	65.76	gold quality
left ovary	UBERON:0002119	65.30	gold quality
tendon	UBERON:0000043	65.05	gold quality
cerebellum	UBERON:0002037	64.82	gold quality
descending thoracic aorta	UBERON:0002345	64.74	gold quality
right ovary	UBERON:0002118	64.67	gold quality
sural nerve	UBERON:0015488	64.64	silver quality
heart left ventricle	UBERON:0002084	63.83	gold quality
gastrocnemius	UBERON:0001388	63.55	gold quality
left adrenal gland	UBERON:0001234	63.54	gold quality
right atrium auricular region	UBERON:0006631	63.53	gold quality
adenohypophysis	UBERON:0002196	63.41	gold quality
left adrenal gland cortex	UBERON:0035825	63.34	gold quality
ileal mucosa	UBERON:0000331	63.23	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-109979	yes	153.00
E-ANND-3	no	2.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting GLIPR1L1, 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-4692	100.00	67.32	2066
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-4424	98.91	70.33	1145
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-6509-5P	97.39	68.27	969
HSA-MIR-331-5P	96.59	67.94	705

Cross-species orthologs

55 orthologs

Organism	Symbol	Gene ID
danio_rerio	glipr1b	ENSDARG00000030078
danio_rerio	glipr2	ENSDARG00000041724
danio_rerio	glipr1a	ENSDARG00000045224
danio_rerio		ENSDARG00000103034
danio_rerio	im:7150988	ENSDARG00000109310
mus_musculus	Glipr1l1	ENSMUSG00000020213
mus_musculus	Glipr1l3	ENSMUSG00000112611
rattus_norvegicus	Glipr1l1	ENSRNOG00000026634
drosophila_melanogaster	Ag5r	FBGN0015010
drosophila_melanogaster	Ag5r2	FBGN0020508
drosophila_melanogaster	CG9400	FBGN0030562
drosophila_melanogaster	CG4270	FBGN0031407
drosophila_melanogaster	CG16995	FBGN0031412
drosophila_melanogaster	CG10651	FBGN0032853
drosophila_melanogaster	CG9822	FBGN0034623
drosophila_melanogaster	CG17974	FBGN0034624
drosophila_melanogaster	CG3640	FBGN0035042
drosophila_melanogaster	CG8072	FBGN0036070
drosophila_melanogaster	CG6628	FBGN0036072
drosophila_melanogaster	scpr-C	FBGN0037879
drosophila_melanogaster	scpr-B	FBGN0037888
drosophila_melanogaster	scpr-A	FBGN0037889
drosophila_melanogaster	CG8483	FBGN0038126
drosophila_melanogaster	CG30486	FBGN0050486
drosophila_melanogaster	antr	FBGN0050488
drosophila_melanogaster	CG31286	FBGN0051286
drosophila_melanogaster	CG32313	FBGN0052313
drosophila_melanogaster	CG32679	FBGN0052679
drosophila_melanogaster	CG34002	FBGN0054002
drosophila_melanogaster	CG34049	FBGN0054049
drosophila_melanogaster	CG17575	FBGN0250842
drosophila_melanogaster	CG42564	FBGN0260766
drosophila_melanogaster	CG42780	FBGN0261848
drosophila_melanogaster	CG43775	FBGN0264297
drosophila_melanogaster	CG43776	FBGN0264298
drosophila_melanogaster	CG43777	FBGN0264299
caenorhabditis_elegans		WBGENE00004742
caenorhabditis_elegans		WBGENE00007397
caenorhabditis_elegans		WBGENE00008027
caenorhabditis_elegans		WBGENE00008028
caenorhabditis_elegans		WBGENE00008029
caenorhabditis_elegans		WBGENE00008030
caenorhabditis_elegans		WBGENE00008625
caenorhabditis_elegans		WBGENE00009891
caenorhabditis_elegans		WBGENE00009895
caenorhabditis_elegans		WBGENE00009896
caenorhabditis_elegans		WBGENE00012816
caenorhabditis_elegans		WBGENE00013971
caenorhabditis_elegans		WBGENE00013972
caenorhabditis_elegans		WBGENE00015246
caenorhabditis_elegans		WBGENE00017055
caenorhabditis_elegans		WBGENE00017183
caenorhabditis_elegans		WBGENE00019178
caenorhabditis_elegans		WBGENE00019179
caenorhabditis_elegans		WBGENE00021780

Paralogs (13): CRISP3 (ENSG00000096006), R3HDML (ENSG00000101074), CRISPLD2 (ENSG00000103196), CRISPLD1 (ENSG00000121005), GLIPR2 (ENSG00000122694), CRISP2 (ENSG00000124490), CRISP1 (ENSG00000124812), PI15 (ENSG00000137558), GLIPR1 (ENSG00000139278), CLEC18B (ENSG00000140839), CLEC18A (ENSG00000157322), CLEC18C (ENSG00000157335), GLIPR1L2 (ENSG00000180481)

Protein

Protein identifiers

GLIPR1-like protein 1 — Q6UWM5 (reviewed: Q6UWM5)

All UniProt accessions (1): Q6UWM5

UniProt curated annotations — full annotation on UniProt →

Function. Required for optimal fertilization at the stage of sperm-oocyte fusion, plays a role in optimizing acrosome function, the translocation of IZUMO1 during the acrosome reaction and the fertilization process. Component of epididymosomes, one type of membranous microvesicules which mediate the transfer of lipids and proteins to spermatozoa plasma membrane during epididymal maturation. Also component of the CD9-positive microvesicules found in the cauda region.

Subunit / interactions. Part of a oolemmal binding multimeric complex (IZUMO1 complex) composed at least of IZUMO1 and GLIPR1L1; the complex assemblage is influenced by the maturation status of the male germ cell. Interacts with IZUMO1.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Cell membrane. Membrane raft. Secreted.

Tissue specificity. Highly expressed in testis.

Post-translational modifications. N-glycosylated. N-glycosylation decreases during the transit in the caput.

Similarity. Belongs to the CRISP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UWM5-1	1, GLIPR1L1beta	yes
Q6UWM5-2	2, GLIPR1L1alpha

RefSeq proteins (2): NP_001291893, NP_689992 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001283	CRISP-related	Family
IPR002413	V5_allergen-like	Family
IPR014044	CAP_dom	Domain
IPR018244	Allrgn_V5/Tpx1_CS	Conserved_site
IPR034121	SCP_GLIPR-1-like	Domain
IPR035940	CAP_sf	Homologous_superfamily

Pfam: PF00188

UniProt features (8 total): signal peptide 1, chain 1, propeptide 1, domain 1, lipid moiety-binding region 1, glycosylation site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWM5-F1	85.30	0.75

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 (1): 221

Glycosylation sites (1): 119

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): GOBP_SINGLE_FERTILIZATION, GOCC_SECRETORY_GRANULE, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, chr12q21, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PLASMA_MEMBRANE_FUSION, GOBP_MEMBRANE_ORGANIZATION, GOBP_FERTILIZATION, GOCC_SECRETORY_VESICLE, GOCC_PROTEIN_COMPLEX_INVOLVED_IN_CELL_ADHESION, GOCC_SIDE_OF_MEMBRANE, GOCC_ACROSOMAL_VESICLE, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY

GO Biological Process (2): fusion of sperm to egg plasma membrane involved in single fertilization (GO:0007342), single fertilization (GO:0007338)

GO Molecular Function (0):

GO Cellular Component (9): acrosomal vesicle (GO:0001669), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), membrane raft (GO:0045121), side of membrane (GO:0098552), protein complex involved in cell-cell adhesion (GO:0098635), extracellular region (GO:0005576), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
single fertilization	1
cellular process involved in reproduction in multicellular organism	1
fertilization	1
secretory granule	1
cell periphery	1
membrane microdomain	1
leaflet of membrane bilayer	1
protein complex involved in cell adhesion	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

448 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLIPR1L1	SPACA7	Q96KW9	567
GLIPR1L1	IZUMO1	Q8IYV9	535
GLIPR1L1	SPACA4	Q8TDM5	526
GLIPR1L1	ELSPBP1	Q96BH3	520
GLIPR1L1	IZUMO2	Q6UXV1	460
GLIPR1L1	SPACA1	Q9HBV2	436
GLIPR1L1	TP53	P04637	428
GLIPR1L1	SPACA9	Q96E40	424
GLIPR1L1	IZUMO4	Q1ZYL8	410
GLIPR1L1	TEX101	Q9BY14	404
GLIPR1L1	SPACA3	Q8IXA5	402
GLIPR1L1	CCDC74B	Q96LY2	402
GLIPR1L1	CCDC169	A6NNP5	391
GLIPR1L1	SPAM1	P38567	389
GLIPR1L1	CIMAP1A	Q96PU9	382

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A6MFK9, A8S6B6, B0VXV6, B7FDI0, B7FDI1, F8J2D4, F8S0Y4, O19010, P0CB15, P0DMT4, P12020, P16563, P48060, P54108, P60623, P79845, P84805, P84808, Q03401, Q2XXP1, Q2XXP2, Q2XXP4, Q2XXP5, Q2XXQ1, Q2XXQ2, Q2XXQ3, Q2XXQ4, Q2XXQ5, Q2XXQ6, Q32LB5, Q3SB03, Q3SB04, Q3SB05, Q3SB06, Q3SB07, Q60477, Q6UWM5, Q7T1K6, Q7ZT98, Q7ZT99

Diamond homologs: A0A182GL09, A0A1S4EWW7, A0A218QX58, A1BQQ5, A6MFK9, A6QLZ7, A8S6B6, A9QQ26, A9YME1, B2MVK7, B9URJ1, C0ITL3, D4B327, D4P2Y4, F8J2D4, G3CJR9, O19010, O43692, P0CB15, P0DMB9, P0DMT4, P0DPU0, P0DPU1, P0DPU2, P0DPU5, P0DPV2, P0DSI3, P10736, P10737, P12020, P16562, P16563, P35759, P35760, P35778, P35779, P35780, P35781, P35782, P35783

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

771 predictions. Top by Δscore:

Variant	Effect	Δscore
12:75363188:GCA:G	donor_gain	1.0000
12:75363191:G:GG	donor_gain	1.0000
12:75347621:GTTA:G	acceptor_gain	0.9900
12:75363099:CAG:C	acceptor_gain	0.9900
12:75363100:A:AG	acceptor_gain	0.9900
12:75363100:AGA:A	acceptor_gain	0.9900
12:75363100:AGAG:A	acceptor_gain	0.9900
12:75363101:G:GG	acceptor_gain	0.9900
12:75363101:GA:G	acceptor_gain	0.9900
12:75363101:GAG:G	acceptor_gain	0.9900
12:75363101:GAGG:G	acceptor_gain	0.9900
12:75363101:GAGGA:G	acceptor_gain	0.9900
12:75368489:T:G	donor_gain	0.9900
12:75363096:TTACA:T	acceptor_loss	0.9800
12:75363097:TACA:T	acceptor_loss	0.9800
12:75363098:ACAG:A	acceptor_loss	0.9800
12:75363100:AG:A	acceptor_loss	0.9800
12:75363097:TACAG:T	acceptor_gain	0.9700
12:75363098:ACAGA:A	acceptor_gain	0.9700
12:75368486:GAGT:G	donor_gain	0.9700
12:75334900:ATGGT:A	donor_loss	0.9500
12:75334903:GTG:G	donor_loss	0.9500
12:75334904:T:TT	donor_loss	0.9500
12:75334905:G:GT	donor_loss	0.9500
12:75363189:CA:C	donor_gain	0.9500
12:75368505:G:GT	donor_gain	0.9500
12:75343934:CACAG:C	donor_loss	0.9400
12:75343935:ACAGG:A	donor_loss	0.9400
12:75343936:CAG:C	donor_loss	0.9400
12:75343937:AGGTA:A	donor_loss	0.9400

AlphaMissense

1597 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:75343698:G:C	W60C	0.997
12:75343698:G:T	W60C	0.997
12:75334861:C:A	R45S	0.996
12:75347707:G:A	C169Y	0.994
12:75343741:T:A	C75S	0.993
12:75343742:G:C	C75S	0.993
12:75343869:G:C	W117C	0.993
12:75343869:G:T	W117C	0.993
12:75347706:T:A	C169S	0.993
12:75347707:G:C	C169S	0.993
12:75347708:C:G	C169W	0.993
12:75334862:G:C	R45P	0.992
12:75347649:G:T	G150C	0.992
12:75343815:T:A	N99K	0.991
12:75343815:T:G	N99K	0.991
12:75343696:T:A	W60R	0.990
12:75343696:T:C	W60R	0.990
12:75347706:T:C	C169R	0.990
12:75343867:T:A	W117R	0.989
12:75343867:T:C	W117R	0.989
12:75347630:G:C	W143C	0.989
12:75347630:G:T	W143C	0.989
12:75347652:T:A	C151S	0.989
12:75347653:G:C	C151S	0.989
12:75347655:G:C	A152P	0.989
12:75347654:T:G	C151W	0.988
12:75347667:T:A	C156S	0.988
12:75347668:G:C	C156S	0.988
12:75363187:T:A	C203S	0.988
12:75363188:G:C	C203S	0.988

dbSNP variants (sampled 300 via entrez): RS1000030049 (12:75347022 T>A), RS1000080217 (12:75346637 C>A,T), RS1000219512 (12:75350123 T>C), RS1000294493 (12:75350414 G>T), RS1000377252 (12:75366330 G>A), RS1000431349 (12:75356242 A>C), RS1000472776 (12:75343001 C>A), RS1000529448 (12:75362260 G>A), RS1000651159 (12:75341520 C>T), RS1000748103 (12:75366581 AAACT>A), RS1000764281 (12:75335773 G>A), RS1000812681 (12:75369426 T>C), RS1000843190 (12:75361402 A>C), RS1000855840 (12:75356515 A>C), RS1000893692 (12:75361115 T>C)

Disease associations

OMIM: gene MIM:610395 | 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

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
terbufos	increases methylation	1
arsenite	increases methylation	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	affects expression	1
Fonofos	increases methylation	1
Folic Acid	decreases expression	1
Parathion	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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