LRIT1

Summary

LRIT1 (leucine rich repeat, Ig-like and transmembrane domains 1, HGNC:23404) is a protein-coding gene on chromosome 10q23.1, encoding Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 1 (Q9P2V4). Photoreceptor synaptic protein essential for normal vision.

Predicted to act upstream of or within phototransduction; synaptic signaling; and visual perception. Predicted to be located in dendrite; endoplasmic reticulum; and membrane. Predicted to be active in endoplasmic reticulum membrane; synapse; and synaptic cleft.

Source: NCBI Gene 26103 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 112 total
• MANE Select transcript: NM_015613

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23404
Approved symbol	LRIT1
Name	leucine rich repeat, Ig-like and transmembrane domains 1
Location	10q23.1
Locus type	gene with protein product
Status	Approved
Aliases	PAL, DKFZP434K091, FIGLER9
Ensembl gene	ENSG00000148602
Ensembl biotype	protein_coding
OMIM	616103
Entrez	26103

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000372105

RefSeq mRNA: 1 — MANE Select: NM_015613 NM_015613

CCDS: CCDS7373

Canonical transcript exons

ENST00000372105 — 4 exons

Exon	Start	End
ENSE00000986139	84237220	84237686
ENSE00000986140	84234073	84234378
ENSE00001456922	84231520	84232903
ENSE00001456927	84241318	84241546

Expression profiles

Bgee: expression breadth tissue_specific, 9 present calls, max score 87.92.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1424 / max 101.8605, expressed in 8 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110386	0.0942	7
110387	0.0393	7
110385	0.0089	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.92	silver quality
Brodmann (1909) area 10	UBERON:0013541	66.14	gold quality
left testis	UBERON:0004533	65.41	gold quality
right testis	UBERON:0004534	65.27	gold quality
testis	UBERON:0000473	63.72	gold quality
frontal pole	UBERON:0002795	63.14	gold quality
middle frontal gyrus	UBERON:0002702	63.02	gold quality
paraflocculus	UBERON:0005351	62.73	gold quality
metanephric glomerulus	UBERON:0004736	59.61	gold quality
mucosa of stomach	UBERON:0001199	51.99	gold quality
sperm	CL:0000019	51.76	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
quadriceps femoris	UBERON:0001377	46.42	gold quality
thymus	UBERON:0002370	46.05	gold quality
vastus lateralis	UBERON:0001379	45.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	43.91	silver quality
amniotic fluid	UBERON:0000173	43.47	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
bone marrow cell	CL:0002092	42.30	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
colonic epithelium	UBERON:0000397	41.21	gold quality
pigmented layer of retina	UBERON:0001782	41.13	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
oviduct epithelium	UBERON:0004804	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting LRIT1, 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-574-5P	100.00	66.01	989
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrit1a	ENSDARG00000019179
danio_rerio	lrit1b	ENSDARG00000099406
mus_musculus	Lrit1	ENSMUSG00000041044
rattus_norvegicus	Lrit1	ENSRNOG00000012790
drosophila_melanogaster	Con	FBGN0005775
drosophila_melanogaster	kek3	FBGN0028370
caenorhabditis_elegans	lron-9	WBGENE00011971
caenorhabditis_elegans		WBGENE00020649

Paralogs (22): CHADL (ENSG00000100399), LGI1 (ENSG00000108231), LGR6 (ENSG00000133067), CHAD (ENSG00000136457), LRIG3 (ENSG00000139263), LGR5 (ENSG00000139292), LRIG1 (ENSG00000144749), LRRTM2 (ENSG00000146006), LGI2 (ENSG00000153012), LGI4 (ENSG00000153902), LRRC52 (ENSG00000162763), ELFN2 (ENSG00000166897), LGI3 (ENSG00000168481), LRG1 (ENSG00000171236), CPN2 (ENSG00000178772), LRIT3 (ENSG00000183423), LRRC26 (ENSG00000184709), LRIG2 (ENSG00000198799), LGR4 (ENSG00000205213), ELFN1 (ENSG00000225968), LRRC24 (ENSG00000254402), TRIL (ENSG00000255690)

Protein

Protein identifiers

Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 1 — Q9P2V4 (reviewed: Q9P2V4)

Alternative names: Leucine-rich repeat-containing protein 21, Photoreceptor-associated LRR superfamily protein, Retina-specific protein PAL

All UniProt accessions (1): Q9P2V4

UniProt curated annotations — full annotation on UniProt →

Function. Photoreceptor synaptic protein essential for normal vision. Involved in synapse formation in cone photoreceptor cells.

Subunit / interactions. May form a homodimer. Interacts with LRIT2; may form a heterodimer with LRIT2. Interacts (via its N-terminal extracellular domain) with metabotropic glutamate receptor GRM6. Interacts (via its extreme C-terminus) with the scaffold protein FRMPD2 (via the third PDZ domain); the interaction leads to their colocalization in photoreceptor synapses.

Subcellular location. Endoplasmic reticulum membrane. Cell projection. Dendrite.

RefSeq proteins (1): NP_056428* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050467	LRFN	Family

Pfam: PF07679, PF13855

UniProt features (23 total): repeat 6, domain 4, sequence variant 4, glycosylation site 3, topological domain 2, signal peptide 1, chain 1, disulfide bond 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2V4-F1	73.66	0.44

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 (1): 275–328

Glycosylation sites (3): 156, 296, 455

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): MODULE_45, GOBP_PHOTOTRANSDUCTION, MODULE_16, GOBP_CELL_CELL_SIGNALING, MODULE_118, MODULE_379, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_RADIATION, GOBP_SYNAPTIC_SIGNALING, GOBP_DETECTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, MODULE_88, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION

GO Biological Process (4): visual perception (GO:0007601), phototransduction (GO:0007602), synaptic signaling (GO:0099536), response to light stimulus (GO:0009416)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): endoplasmic reticulum membrane (GO:0005789), dendrite (GO:0030425), synaptic cleft (GO:0043083), synapse (GO:0045202), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
sensory perception of light stimulus	1
signal transduction	1
detection of light stimulus	1
cell-cell signaling	1
synapse	1
response to radiation	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
neuron projection	1
dendritic tree	1
extracellular region	1
cell junction	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2030 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRIT1	MANSC4	A6NHS7	618
LRIT1	CDHR1	Q96JP9	564
LRIT1	HOMEZ	Q8IX15	527
LRIT1	TTC38	Q5R3I4	525
LRIT1	TSPAN10	Q9H1Z9	494
LRIT1	SAMD7	Q7Z3H4	489
LRIT1	DDX28	Q9NUL7	488
LRIT1	EID2B	Q96D98	471
LRIT1	RGR	P47804	459
LRIT1	PPEF2	O14830	447
LRIT1	WDR17	Q8IZU2	434
LRIT1	BMS1	Q14692	420
LRIT1	GPR15LG	Q6UWK7	399
LRIT1	CLDND1	Q9NY35	399
LRIT1	LAD1	O00515	381

IntAct

2 interactions, top by confidence:

A	B	Type	Score
LRIT1	SIGLEC6	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): LRIT1 (Affinity Capture-Western)

ESM2 similar proteins: A1A4H9, A2ARI4, A6NDA9, B0BLW3, B4F7C5, D3ZAL8, D3ZTV3, D4A6D8, D4A7P2, E7FE13, F1MT22, O14498, O43155, O43300, P0DM44, P83286, Q149C3, Q5NVQ6, Q5R6B1, Q5R7M3, Q5RAC4, Q6PFC5, Q6RKD8, Q80WD0, Q80XG9, Q80ZD7, Q80ZD8, Q80ZD9, Q810C0, Q810C1, Q86SJ2, Q86UE6, Q86UN2, Q86VH4, Q86VH5, Q86WK6, Q8BGA3, Q8BLU0, Q8BZ81, Q8C2S7

Diamond homologs: A0A087WV53, A1KZ92, A2AJ76, A4IFW2, A4IGL7, A6NDA9, B0BNK7, B0V2N1, D2HFT7, D3YXG0, D4A1J9, D4ABX8, F1NWE3, G5EG78, O15146, O73775, O75325, O94898, P07722, P15364, P20916, P20917, P23468, P43146, P48960, P53813, P70193, P70211, Q03142, Q08761, Q08879, Q13332, Q13449, Q1ENI8, Q1RMS4, Q1WIM1, Q21038, Q24372, Q26474, Q2Q421

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

498 predictions. Top by Δscore:

Variant	Effect	Δscore
10:84232904:C:CC	acceptor_gain	1.0000
10:84234220:T:TA	donor_gain	1.0000
10:84234375:AGCC:A	acceptor_gain	1.0000
10:84234376:GCC:G	acceptor_gain	1.0000
10:84234377:CCC:C	acceptor_gain	1.0000
10:84234379:C:CC	acceptor_gain	1.0000
10:84234380:T:A	acceptor_loss	1.0000
10:84234387:G:GC	acceptor_gain	1.0000
10:84232900:TGCA:T	acceptor_gain	0.9900
10:84232902:CA:C	acceptor_gain	0.9900
10:84232903:AC:A	acceptor_loss	0.9900
10:84232905:T:G	acceptor_loss	0.9900
10:84234069:ATAC:A	donor_loss	0.9900
10:84234071:A:AT	donor_loss	0.9900
10:84234072:C:G	donor_loss	0.9900
10:84234221:C:A	donor_gain	0.9900
10:84234374:TAGCC:T	acceptor_gain	0.9900
10:84234377:CC:C	acceptor_gain	0.9900
10:84234378:CC:C	acceptor_gain	0.9900
10:84234382:C:CT	acceptor_gain	0.9900
10:84234383:A:T	acceptor_gain	0.9900
10:84234387:G:C	acceptor_gain	0.9900
10:84237690:C:CC	acceptor_gain	0.9900
10:84232895:CCTGG:C	acceptor_gain	0.9800
10:84232899:GTGCA:G	acceptor_gain	0.9800
10:84232901:GCA:G	acceptor_gain	0.9800
10:84232902:CAC:C	acceptor_gain	0.9800
10:84237682:CTGTC:C	acceptor_gain	0.9800
10:84237685:TC:T	acceptor_loss	0.9800
10:84237685:TCCTG:T	acceptor_gain	0.9800

AlphaMissense

4012 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:84234359:C:A	W203C	0.998
10:84234359:C:G	W203C	0.998
10:84234107:C:A	W287C	0.996
10:84234107:C:G	W287C	0.996
10:84232803:G:C	N332K	0.994
10:84232803:G:T	N332K	0.994
10:84234361:A:G	W203R	0.994
10:84234361:A:T	W203R	0.994
10:84237314:G:C	N165K	0.991
10:84237314:G:T	N165K	0.991
10:84237315:T:A	N165I	0.991
10:84232457:A:G	W448R	0.990
10:84232457:A:T	W448R	0.990
10:84234109:A:G	W287R	0.990
10:84234109:A:T	W287R	0.990
10:84234273:C:G	C232S	0.989
10:84234274:A:T	C232S	0.989
10:84232816:C:G	C328S	0.988
10:84232817:A:T	C328S	0.988
10:84234365:G:C	N201K	0.988
10:84234365:G:T	N201K	0.988
10:84234367:T:A	N201Y	0.987
10:84237458:G:C	N117K	0.987
10:84237458:G:T	N117K	0.987
10:84232197:A:C	S534R	0.986
10:84232197:A:T	S534R	0.986
10:84232199:T:G	S534R	0.986
10:84234354:C:T	C205Y	0.986
10:84234216:C:G	C251S	0.985
10:84234217:A:T	C251S	0.985

dbSNP variants (sampled 300 via entrez): RS1000420650 (10:84240748 T>G), RS1000455378 (10:84242223 G>C), RS1000538967 (10:84231123 T>C), RS1000743999 (10:84236140 C>T), RS1000756693 (10:84241753 C>T), RS1001071812 (10:84235969 A>C), RS1001512828 (10:84234289 C>A), RS1001736687 (10:84239987 G>A), RS1001998708 (10:84241142 C>A,T), RS1002250016 (10:84235720 C>T), RS1002256878 (10:84237084 A>C), RS1002541576 (10:84233589 T>C), RS1002741087 (10:84238497 G>A), RS1002963894 (10:84233905 A>G,T), RS1003371441 (10:84238162 T>C)

Disease associations

OMIM: gene MIM:616103 | 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
GCST006291_113	Spherical equivalent or myopia (age of diagnosis)	9.000000e-17
GCST010002_293	Refractive error	1.000000e-70

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	decreases methylation	1
bisphenol A	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	increases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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