LRIT3

leucine rich repeat, Ig-like and transmembrane domains 3, the group of I-set domain containing

Basic information

Region (hg38): 4:109848106-109872315

Links

ENSG00000183423 ∙ NCBI:345193 ∙ OMIM:615004 ∙ HGNC:24783 ∙ Uniprot:Q3SXY7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital stationary night blindness 1F (Strong), mode of inheritance: AR
• congenital stationary night blindness 1F (Moderate), mode of inheritance: AR
• congenital stationary night blindness (Supportive), mode of inheritance: AD
• congenital stationary night blindness 1F (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Night blindness, congenital stationary, type 1F	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	23246293

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LRIT3 gene.

• not provided (334 variants)
• Congenital stationary night blindness 1F (61 variants)
• Inborn genetic diseases (31 variants)
• Congenital Stationary Night Blindness, Recessive (23 variants)
• not specified (10 variants)
• Stargardt disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRIT3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	74	5	83
missense			192	11	8	211
nonsense	1		8			9
start loss			2			2
frameshift			8			8
inframe indel			3	1		4
splice donor/acceptor (+/-2bp)			1			1
splice region			5	4		9
non coding			13	19	12	44
Total	1	0	231	105	25

Variants in LRIT3

This is a list of pathogenic ClinVar variants found in the LRIT3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-109848188-C-G		Congenital Stationary Night Blindness, Recessive	Likely benign (Jun 14, 2016)
4-109848202-A-G			Uncertain significance (Sep 09, 2022)
4-109848204-G-A			Uncertain significance (Feb 02, 2022)
4-109848206-A-T			Uncertain significance (Dec 11, 2023)
4-109848216-ATGTCTGTGCAT-A			Uncertain significance (Feb 18, 2022)
4-109848216-A-AAT		Congenital stationary night blindness 1F	Uncertain significance (May 02, 2018)
4-109848220-C-T			Likely benign (Mar 03, 2020)
4-109848222-G-C			Likely benign (Nov 27, 2023)
4-109848231-C-A		Congenital stationary night blindness 1F • LRIT3-related disorder	Conflicting classifications of pathogenicity (Jan 22, 2024)
4-109848248-G-A			Uncertain significance (Mar 14, 2022)
4-109848248-G-T			Uncertain significance (Oct 17, 2022)
4-109848252-G-C			Likely benign (Feb 18, 2022)
4-109848254-G-A			Uncertain significance (Dec 24, 2021)
4-109848258-TTTG-T		Stargardt disease	Pathogenic (Dec 13, 2022)
4-109848264-T-C			Likely benign (Jul 12, 2022)
4-109848276-C-T			Likely benign (Jul 08, 2020)
4-109848292-G-A			Uncertain significance (Aug 27, 2021)
4-109848300-T-C		Congenital stationary night blindness 1F	Conflicting classifications of pathogenicity (Jun 13, 2023)
4-109848303-C-T			Likely benign (Dec 07, 2022)
4-109848304-G-A			Uncertain significance (Feb 28, 2022)
4-109848315-A-C			Likely benign (Nov 18, 2023)
4-109848321-T-C			Uncertain significance (May 27, 2022)
4-109848323-C-T			Uncertain significance (Apr 18, 2022)
4-109848325-C-T			Likely benign (May 18, 2022)
4-109848337-A-G			Likely benign (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LRIT3	protein_coding	protein_coding	ENST00000594814	4	24114

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.04e-11	0.0668	125718	0	29	125747	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.314	319	335	0.952	0.0000166	4390
Missense in Polyphen		76	112.57	0.67511		1464
Synonymous	0.500	123	130	0.944	0.00000656	1390
Loss of Function	0.204	17	17.9	0.948	8.40e-7	275

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000271	0.000271
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000142	0.000141
Middle Eastern	0.0000544	0.0000544
South Asian	0.000141	0.000131
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required in retinal ON-bipolar cells for normal localization of the cation channel TRPM1 at dendrite tips (By similarity). May also have a role in cone synapse formation (By similarity). Might facilitate FGFR1 exit from the endoplasmic reticulum to the Golgi (PubMed:22673519). Could be a regulator of the FGFRs (PubMed:22673519). {ECO:0000250|UniProtKB:W8DXL4, ECO:0000269|PubMed:22673519}.
• Disease: DISEASE: Night blindness, congenital stationary, 1F (CSNB1F) [MIM:615058]: An autosomal recessive form of congenital stationary night blindness, a non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. {ECO:0000269|PubMed:23246293}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: 1.91
• rvis_percentile_EVS: 97.42

Haploinsufficiency Scores

• pHI: 0.0498
• hipred: N
• hipred_score: 0.144

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0699

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Lrit3
• Phenotype: vision/eye phenotype

Gene ontology

• Biological process: visual perception;regulation of fibroblast growth factor receptor signaling pathway;response to stimulus
• Cellular component: endoplasmic reticulum membrane;integral component of membrane;dendrite;perikaryon