LRIT3

protein-coding

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

Gene summary

This gene encodes a protein that has a fibronectin type III domain and a C-terminal transmembrane domain, as well as a leucine-rich repeat domain and immunoglobulin-like domain near the N-terminus. The encoded protein may regulate fibroblast growth factor receptors and affect the modification of these receptors, which are glycosylated differently in the Golgi and endoplasmic reticulum. Mutations in this gene are associated with congenital stationary night blindness, type 1F. [provided by RefSeq, May 2013]

MANE transcript

NM_198506.5

Inheritance

AD, AR

ClinVar variants

P:6U:247B:138

Top phenotype

Night blindness, congenital stationary, type 1F

gnomAD constraint

pLI —, LoF o/e 0.95

Max pathogenic AF

—

Genomic locus

chr4:109,848,107-109,872,315

External References & Databases

Ensembl (ENSG00000183423)

Transcript & Mutation Effects

hg38 • Region Span ~24.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital stationary night blindnessSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016293

Submitter: Orphanet

congenital stationary night blindness 1FSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014026

Submitter: Labcorp Genetics (formerly Invitae)

congenital stationary night blindness 1FSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014026

Submitter: PanelApp Australia

congenital stationary night blindness 1FSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014026

Submitter: G2P

congenital stationary night blindness 1FMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014026

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Night blindness, congenital stationary, type 1FAR

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Refs: 23246293

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LRIT3 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 364

Inborn genetic diseasesTotal: 94

Congenital stationary night blindness 1FTotal: 41

LRIT3-related disorderTotal: 10

not specifiedTotal: 7

Stargardt diseaseTotal: 2

Retinal dystrophyTotal: 2

Optic atrophyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198506.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	113 clinvar	3 clinvar	118
missense			227 clinvar	18 clinvar	4 clinvar	249
nonsense	2 clinvar	2 clinvar	7 clinvar			11
start loss			2 clinvar			2
frameshift	1 clinvar	1 clinvar	8 clinvar			10
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	3	3	247	131	7	391

Highest pathogenic variant AF is 0.000013010959

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_198506.5	RefSeq	NP_940908.3	4	MANE Select
ENST00000594814.6	Ensembl	ENSP00000469759.1	4	MANE Select
ENST00000327908.3	Ensembl	ENSP00000328222.3	3	Standard
ENST00000876618.1	Ensembl	ENSP00000546677.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000594814
Coding exons: 4
Length: 24114
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125747
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.314	319	335	0.952	0.0000166	4390
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00014	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0699

Gene Damage Prediction

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