SIPA1L3

signal induced proliferation associated 1 like 3, the group of PDZ domain containing

Basic information

Region (hg38): 19:37907208-38208369

Links

ENSG00000105738

∙ NCBI:23094 ∙ OMIM:616655 ∙ HGNC:23801 ∙ Uniprot:O60292 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

total early-onset cataract (Supportive), mode of inheritance: AD
cataract 45 (Limited), mode of inheritance: Semidominant
cataract 45 (Limited), mode of inheritance: AR
cataract 45 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 45	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	25804400

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SIPA1L3 gene.

not_specified (286 variants)
not_provided (202 variants)
SIPA1L3-related_disorder (27 variants)
Cataract_45 (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIPA1L3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015073.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	54 clinvar	17 clinvar	73
missense			324 clinvar	28 clinvar	10 clinvar	362
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	2	0	327	82	27

Highest pathogenic variant AF is 0.0000027365097

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SIPA1L3	protein_coding	protein_coding	ENST00000222345	20	301145

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000366	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.55	1018	1.17e+3	0.872	0.0000805	11499
Missense in Polyphen		296	410.29	0.72144		4033
Synonymous	-0.659	555	536	1.04	0.0000421	3721
Loss of Function	6.72	7	65.9	0.106	0.00000352	715

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000188	0.000180
Ashkenazi Jewish	0.000403	0.000397
East Asian	0.0000548	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000191	0.000176
Middle Eastern	0.0000548	0.0000544
South Asian	0.0000986	0.0000980
Other	0.000352	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens (PubMed:26231217). {ECO:0000269|PubMed:26231217}.;
Disease: DISEASE: Note=A chromosomal translocation involving SIPA1L3 is found in a patient with bilateral severe ocular abnormalities including congenital cataracts, corneal clouding, iridocorneal and lenticular adhesions and microphthalmia. Chromosomal translocation t(2;19)(q37.3;q13.1). In addition to translocation, missense variant has been found in patient with bilateral congenital cataracts (PubMed:26231217). {ECO:0000269|PubMed:26231217}.; DISEASE: Cataract 45 (CTRCT45) [MIM:616851]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. {ECO:0000269|PubMed:25804400}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Rap1 signaling pathway - Homo sapiens (human) (Consensus)

Recessive Scores

pRec: 0.110

Intolerance Scores

loftool: 0.132
rvis_EVS: -1.61
rvis_percentile_EVS: 2.95

Haploinsufficiency Scores

pHI: 0.489
hipred: Y
hipred_score: 0.563
ghis: 0.616

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.930

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Sipa1l3
Phenotype: vision/eye phenotype;

Zebrafish Information Network

Gene name: sipa1l3
Affected structure: eye
Phenotype tag: abnormal
Phenotype quality: perforate

Gene ontology

Biological process: eye development;hematopoietic progenitor cell differentiation;epithelial cell morphogenesis;cytoskeleton organization;positive regulation of GTPase activity;regulation of small GTPase mediated signal transduction;establishment of epithelial cell polarity
Cellular component: stress fiber;extracellular space;apical plasma membrane;apical part of cell;tricellular tight junction
Molecular function: GTPase activator activity